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Biomedical subjects

J Lemerle

Publications and source records attributed to J Lemerle.

At least 181 records · Page 10Linked to original sources

[Fall in the levels of circulating lymphoblasts caused by intravenous administration of the A50 monoclonal antibody in a patient with acute T-cell lymphoblastic leukemia. A step in the demonstration of serotherapy with monoclonal antibodies].

In an 8-year-old boy with acute lymphoblastic leukaemia not previously treated intravenous administration of a single 8 mg dose of a monoclonal antibody that recognizes an epitope restricted to the surface of mature T-cells resulted, within 20 hours, in a fall in circulating lymphoblasts from 200 000 to 70 000. No adverse clinical or biological reaction was detected and no antigenic modulation occurred at lymphoblast surface. This observation constitutes a first step in the complex development of effective serotherapy for malignant diseases, using monoclonal antibodies.

Animals↗

[Adjuvant therapy in the management of osteosarcomas: the O3 trial (EORTC and ISPO) ].

The European Organization for Research on the Treatment of Cancer (EORTC) and the international Society of Pediatric Oncology (ISPO) have set up a randomized controlled trial designed to compare three different regimens of adjuvant therapy applied after treatment of the primary tumor (usually by radical surgery): a prolonged course of chemotherapy (41 weeks) combining adriamycin, methotrexate in high doses followed by folinic acid, vincristine, and cyclophosphamide; radiotherapy delivering 20 grays to the lungs; and a short course of chemotherapy (8 weeks) combining adriamycin, methotrexate in high doses, folinic acid and vincristine, associated with irradiation of the lungs as in the preceding protocol. At the time being, 156 patients have been included in this study. If conclusions are to be drawn from this trial, a total of 300 patients seems necessary.

Antineoplastic Agents↗

The correlation of adenosine deaminase and purine nucleoside phosphorylase activities in human lymphocytes subpopulations and in various lymphoid malignancies.

Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) were measured in normal human and in malignant lymphoid cells. Thymocytes had high ADA activity (21.2 +/- 6.8 10(3) nM/h/mg) and low PNP activity (1.2 +/- 0.6), whereas T peripheral blood lymphocytes (PBL) had low ADA activity (1.20 +/- 0.22) and high PNP activity (2.8 +/- 1.3). Moreover cortico-thymocytes had higher ADA and lower PNP levels than medullary thymocytes. A linear correlation was observed between ADA and PNP activities in both thymocytes and T-PBL. Cells from 13 patients with T acute lymphoblastic leukemia (ALL) and 10 patients with T lymphoblastic lymphoma (LL) had very high levels of ADA (respectively 13.0 +/- 5.4 and 22.8 +/- 14) and low levels of PNP (respectively 1.9 +/- 0.8 and 2.5 +/- 1.4). However no clear relationship appeared between subgroups of these T-cell malignancies defined by their patterns of surface antigens, revealed by reactivity with monoclonal antibodies, and ADA and PNP levels, and there was no correlation between the two enzymes. In contrast, cells from 31 patients with HLA-DR+ common ALL had significantly low values of ADA as compared to cells from six patients with HLA-DR- common ALL and a linear correlation was observed between ADA and PNP in cells from children with non-T, non-B ALL. These results show that specific stages of T-cell development may be characterized by the relationships and the correlation between the two enzymes and suggest that T-ALL and T-LL appear to be the group of lymphoid malignancies with a high degree of incoordination between ADA and PNP activities.

Adenosine Deaminase↗

Probing human malignant T cells with lectins: a comparison with their surface antigen patterns defined by monoclonal antibodies.

Tumor cells from 40 children and 13 adults with T cell malignancies were assessed for staining with fluorescinated peanut agglutinin (PNA) and soybean agglutinin (SBA). These cell populations had also been characterized for surface surface antigens using a series of monoclonal antibodies (Mo. Ab.) that permit an assignment of malignant cells to discrete stages of normal T cell differentiation. We had previously shown a clear correspondence between lectin- and Mo. Ab-defined cell compartments within thymuses from normal children and T cells in peripheral blood. We report here that the pattern of reactivity of malignant T cells populations with lectins correlates closely the degree of maturation, as assessed by Mo. Ab. Thus, utilization of lectins together with Mo. Ab., can be clinically useful to characterize T cell malignancies. This observation shows that, in spite of a high degree of heterogeneity of malignant T cell populations from one patient to the other, in their pattern of surface antigens, these populations seem essentially to conform to the scheme of normal T cell differentiation.

Antibodies, Monoclonal↗

Effects of pulmonary function of whole lung irradiation for Wilm's tumour in children.

The effect of whole lung irradiation on lung function was investigated in 48 children treated for Wilm's tumour with pulmonary metastases. Lung function tests were performed before irradiation and were repeated annually for as long as possible, the length of follow-up varying from two to 17 years. A reduction in both lung volume and in dynamic compliance was clearly observed. In some patients these changes occurred in the early post-irradiation months, but in most the decrease observed progressed over longer periods of time. Static pressure volume curves, blood-gases, and carbon monoxide transfer were normal. These findings make it unlikely that post-irradiation pulmonary fibrosis was involved. Another explanation for the decreased lung volume and dynamic compliance might be failure of alveolar multiplication. Muscular injury is unlikely as the patients were able to produce normal transthoracic pressures. A failure of chest wall growth is also possible and would explain the progressive restrictive impairment but not the early lung function changes. It is suggested that the early effects detected in some patients were the result of lung injury and that later effects resulted from impaired chest wall growth.

Child↗

Effect of hypothalamic and pituitary irradiation on pubertal development in children with cranial tumors.

The purpose of the present study was to report on gonadotropin function and puberty of a large group of children treated by cranial irradiation for cranial and neck tumors and medulloblastoma. Forty-five children of pubertal age were investigated. The mean interval time since radiation was 5 2/12 yr. Gonadotropin and gonadal function were evaluated by clinical criteria, plasma sex steroids, and plasma LH and FSH responses to LRH. Puberty was complete or progressing normally in 31 cases and was abnormal in 14 cases. Severe gonadotropin deficiency, with lack of or slow progression of puberty and decreased LH and FSH responsiveness to LRH, was observed in 5 cases; 2 of these had moderately elevated plasma PRL levels. Secondary amenorrhea or lack of pubertal progression was found in 5 other cases. GH deficiency was associated with gonadotropin deficiency in 9 of these 10 cases. Adrenal function, estimated by basal dehydroisoepiandrosterone, dehydroisoepiandrosterone sulfate, and estrone, was normal according to pubic hair stages. In conclusion, complete or partial gonadotropin deficiency can be the consequence of cranial irradiation in children receiving 6000 rads or less. It is usually associated with GH deficiency. The site of the damage on the pituitary gland or the hypothalamus remains to be demonstrated.

Adolescent↗

Changes in surface antigens on malignant T cells from lymphoblastic lymphomas at relapse: an appraisal with monoclonal antibodies and microfluorometry.

By using a panel of monoclonal antibodies reactive with lymphoid differentiation antigens and microfluorometry, we investigated the malignant cells from five patients with T-cell lymphoblastic lymphoma both at initial involvement and at relapse. We have observed changes in cell surface antigens densities in four of the five cases. These changes could be interpreted as a shift in the status of differentiation of the malignant cells. In two cases the malignant cells appeared to be arrested at an earlier stage at relapse than at initial involvement, while in the two other cases, cells at relapse appeared to be arrested at a later stage than at initial involvement. Interestingly, a parallelism was observed between regression of the differentiative status of the malignant T cells and "leukemic conversion." These observations are also relevant to the understanding of the development of tumor resistance to chemotherapy.

Adolescent↗

Non-T, non-B lymphomas are rare in childhood and associated with cutaneous tumor.

Tumor cells from a total of 116 children with non-Hodgkin's lymphoma were studied for their pattern of reactivity with a battery of cell markers, including their capacity for spontaneous formation of sheep erythrocyte rosettes (E-rosettes), demonstration of surface immunoglobulins (SIg), and positivity with antisera against T-cell antigens, the common acute-lymphoblastic-leukemia-associated antigen (cALLa), and Ia-like antigens. Fifty-eight children (50%) had T-cell lymphomas, including all those with mediastinal tumors. Fifty children (43%) had B-cell lymphomas, including 44 of the 45 with abdominal primaries. Eight children (7%) had non-T, non-B tumors, 4 of whom presented at a young age with cutaneous lymphoblastic tumors. These results demonstrate that the great majority of children with NHL, not leukemic at diagnosis, have tumors clearly committed to either T- or B-cell differentiation pathways and only rarely exhibit the common ALL phenotype (cALLa+, Ia+, E-, T-, SIg-), contrasting with the distribution of childhood lymphoblastic leukemias. The unusual association of these non-T, non-B cases with skin involvement has not previously been reported, raising speculation regarding patterns of lymphocyte traffic and origins of childhood lymphomas and leukemias.

Adolescent↗

[Thalamic tumors in children. A study of 38 cases (author's transl)].

The main clinical, evolutive and therapeutic features of thalamic tumors are reviewed in 38 children. Signs of increased intracranial pressure (76% of the cases) and of controlateral hemiparesis of varying degree (76% of the cases) were the main clinical symptoms. CT-scan is the best means of investigation. Therapeutic protocols that seem to obtain the best results consist of radiotherapy (between 45 and 55 grays) associated with shunting, when intracranial hypertension results from obstruction of an interventricular foramen by the tumor. Surgery is contra-indicated in most tumors in this area.

Adolescent↗

[The treatment of Wilm's tumor, improvements and new trends. A study of 724 cases treated at the Gustave-Roussy Institute. 1952-1980 (author's transl)].

Study of 724 cases of Wilm's tumor treated between 1952 and 1980 at the Gustave-Roussy Institute, according to 5 successive therapeutic protocols with or without chemotherapy (Actinomycin alone or Actinomycin and Vincristine). Recovery rates change from 44 to over 90% during this period. Improvement of survival was first obtained by the efficient treatment of metastases, then by preventing their development with systematic chemotherapy with Actinomycin and Vincristine. Rate of survival without relapse changed from 38 to 71 and 86%. Thus, the decrease in the number of patent metastases subjected to heavy treatments responsible for severe respiratory and orthopedic sequelae improved the quality of survival of these children.

Adolescent↗

Cell surface characterization of malignant T cells from lymphoblastic lymphoma using monoclonal antibodies: evidence for phenotypic differences between malignant T cells from patients with acute lymphoblastic leukemia and lymphoblastic lymphoma.

A series of monoclonal antibodies was used for the characterization of malignant T cells from 21 patients with lymphoblastic lymphoma (LL). The tumor population from these patients showed a marked degree of phenotypic heterogeneity and a proportion (one-third) of patients had tumor cells that did not conform exactly with the cells normally detected in the thymus. However, these cell populations could be related to the early or common or late thymocyte population (about one-third of the patients in each category). This contrast, with the characterization of malignant T cells from 43 patients with acute lymphoblastic leukemia (ALL) that could be related to either early or common thymocytes, with an exception of two patients categorized as having a tumor population related to late thymocytes. Further phenotypic differences between cells from ALL and LL could be demonstrated by investigation with two additional monoclonal antibodies, A50 and U4. Among patients with malignant T cells related to common thymocyte, 0/12 patients with ALL had cells recognized by A50, where 5/8 patients with LL had A50+ cells. Among patients with early thymocytes, only patients with ALL had cells recognized by U4. In addition, 5 LL patients had cells reactive with J5, a monoclonal antibody recognizing the common ALL antigen (CALLA). Since CALLA was found on cells related to common and late thymocytes, CALLA is neither lineage specific, nor can it be viewed as being peculiar to malignant lymphoid cells arrested at very immature stages of differentiation.

Adolescent↗

Correspondence between lectin-defined and surface antigen-defined cell subpopulations in the human thymus: its variation during ontogeny.

In the thymus of children, congruent to 50% of cells are recognized both by peanut agglutinin and soybean agglutinin (PNA+, SBA+), congruent to 23% of cells are PNA-, SBA-, and 23% are PNA-, SBA+. This pattern of recognition was compared with the reactivity of these cells with monoclonal antibodies recognizing T cell differentiation antigens A 50 and a series (T3, T6, T8) that defines 3 discrete stages of T cell differentiation. Most PNA+, SBA+ display T6 and T8 but not T3 antigens; most PNA-, SBA+ display T3+ and A 50+ but not T6; and T3-, T6-, A 50- cells are PNA-, SBA-. Thus, there is a close correspondence between PNA+, SBA+ cells and the common (cortical) T3-, T6+ thymocytes; between PNA-, SBA+ cells and late (medullary) T3+, T6- thymocytes; and between PNA-, SBA- cells and early thymocytes. During ontogeny, although there are fewer PNA+ cells in the thymus, the proportion of T3+ cells, T6+ cells, and T3-, T6- cells showed no major modification as early as 16 wk.

Agglutinins↗

Surface antigens on malignant Sézary and T-CLL cells correspond to those of mature T cells.

Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T-cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sézary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T-chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.

Antibody Specificity↗