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Biomedical subjects

R Bataille

Publications and source records attributed to R Bataille.

At least 199 records · Page 11Linked to original sources
PubMed1988

In vitro production of beta 2 microglobulin by human myeloma cells.

Serum beta 2 microglobulin (B2M) has recently been shown to be a powerful, although nonspecific, marker of multiple myeloma (MM) disease activity. Since the nature of cells producing high levels of B2M remains obscure in MM, we measured (in vitro) the spontaneous secretion of free B2M in 58 culture samples from 52 patients with MM. In comparison with samples from normal individuals and from individuals with monoclonal gammopathy of unknown significance, an abnormal secretion of B2M was found in 83% of samples containing myeloma cells. Levels of secretion significantly correlated with the percentage of tumor cells, tumor progression, and moreover, with the immunoglobulin type of the tumor. The highest levels of secretion were noted in IgG and IgA MM. Our present results would favor the hypothesis of a direct secretion of B2M by myeloma cells and emphasize the interest of B2M as a marker in a majority of (but not all) patients with MM.

Biomarkers, Tumor↗
PubMed1987

Production of growth factors by human myeloma cells.

Using in vitro-growing myeloma cell lines, we studied the growth factors involved in human multiple myeloma, and particularly the potential of autocrine secretion and response to B-cell growth factor (BCGF) of RPMI 8226, the best-documented Epstein-Barr virus-negative human myeloma cell line. We found that three myeloma cell lines (RPMI 8226, U266, and IM9) produce an autostimulatory growth factor (AGF) and thus increase their own proliferation by 2- to 3-fold in cells cultured at low density. Optimal AGF production was obtained after 24 h of culture at a cell density ranging from 2.5 to 5 million cells/ml. The three myeloma cell lines produce type II BCGF, able to induce the proliferation of highly purified human peripheral blood B-cells, only after anti-mu activation. The BCGF produced by RPMI 8226 can be absorbed onto RPMI 8226 cells together with the RPMI 8226 AGF, and the two are copurified on gel filtration in a peak with an apparent molecular weight of 70,000. RPMI 8226 can be efficiently activated by human high molecular weight BCGF II (Mr 50,000) and less extensively by BCGF I (Mr 12,000). RPMI 8226 does not produce either detectable IL1 or interferons gamma and alpha and IL1 and gamma-IFN had no stimulating effect on RPMI 8226 proliferation. Our findings support the conclusion that RPMI 8226 produces a BCGF II working as an AGF.

Burkitt Lymphoma↗
PubMed1987

Serum bone gla-protein in multiple myeloma.

Serum bone gla-protein (SBGP), a marker of bone formation, was measured by radioimmunoassay in 57 patients with multiple myeloma (MM) and correlated with presenting features and disease activity. As a whole, patients with MM did not differ from normal controls or from patients with a monoclonal gammopathy of undetermined significance, but a significant percentage of abnormal values of SBGP was found in this MM population (18% of cases, P less than 0.005). At the time of diagnosis, SBGP was significantly lower in advanced disease (Stage III) than in less active disease (Stage I and II) with mean values of 4.4 +/- 2.7 ng/ml and 7.1 +/- 1.9 ng/ml, respectively (P less than 0.02). SBGP levels inversely correlated with the severity of the disease, the lowest values being observed in patients with extensive lytic bone lesions frequently associated with hypercalcemia (2.9 +/- 1.7 ng/ml). These data suggest the presence of a strong osteoblastic inhibition, at the body level, in the majority of patients (80%) with active osteoclastic MM (uncoupled process). However, a small subset of myeloma patients (20%) presented coupled MM, as defined by increased bone resorption (i.e., lytic bone lesions +/- hypercalcemia) and increased bone formation (i.e., increased SBGP values). Similar features of coupling-uncoupling were observed during disease progression. Finally, serial studies performed in 15 patients confirm these findings and the relation of SBGP levels to disease activity. Of major interest was the observation of a return of SBGP levels from low to normal values during remission induction, after successful completion of a plateau phase. According to these data, SBGP appears to be a new and promising marker for the clinical evaluation of MM.

Adult↗
PubMed1987

B cell malignancies presenting with unusual bone involvement and mimicking multiple myeloma. Study of nine cases.

Nine unusual cases of B cell malignancies presenting with lytic bone lesions on radiography and/or hypercalcemia, and mimicking multiple myeloma are reported in this study. These cases included acute lymphoblastic leukemia (one patient), non-Hodgkin's lymphoma (five patients), chronic lymphocytic leukemia (two patients), and Waldenström's disease (one patient). Quantitative bone biopsy performed in two patients (one with non-Hodgkin's lymphoma and one with Waldenström's disease) demonstrated a dramatic increase in osteoclastic resorption close to tumor cells in both cases, similar to or even more marked than that observed in multiple myeloma. Finally, significant production of bone resorbing activity was found in short-term liquid culture specimens of tumor cells in eight of the nine cases. These observations clearly indicate that in B cell disorders other than multiple myeloma, the malignant B cells can produce significant bone resorbing activity in vitro and result in excessive osteoclastic resorption and lytic bone lesions, frequent hypercalcemia, and an overall disease picture clinically mimicking multiple myeloma.

Adolescent↗
PubMed1987

[Immunology of myeloma].

Multiple myeloma (MM) is the most common malignant plasma cell dyscrasia. It is defined as the malignant expression of clonal expansion (in blood and bone marrow) of idiotypic B lymphoid cells (B id+) with proliferation, asynchronic maturation, and abnormal secretion of idiotypic plasma cells, initially maintained in the bone marrow. Malignancy includes: suppression of nonidiotypic (= polyclonal) B cell activation, suppression of normal hematopoiesis, and excessive osteoclastic resorption, via the production of osteoclast activating factors by myeloma cells. In MM, tumor growth is initially very slow in bone marrow (= chronic phase), controlled by chemotherapy or spontaneously controlled (= indolent variant). Terminal disease is marked by uncontrolled and fast tumor growth with extramedullary involvement of tumor cells (= fulminant or acute phase). Clonal evolution with chromosomal changes (chromosomes 1, 11, 14) is generally involved in the growth pattern changes. The nature of the oncogenic event and of the myeloma stem cell remains unknown.

B-Lymphocytes↗
PubMed1987

[Contribution of bone biopsy with histomorphometry in the evaluation of monoclonal gammopathy].

Histomorphometric analysis of bone specimen from the iliac crest was performed to determine total trabecular resorption surface (TTRS) in 46 patients presenting with a monoclonal gammopathy, which was benign in 17 cases and malignant in 29 others. In benign gammopathies, 14 patients had normal TTRS; no adverse progression, representing a malignant B-cell lymphoproliferative disorder occurred after 40 months of follow-up. The three other patients presented increased areas of resorption in contact with lymphoplasmocyte nodules or pure plasmocytes and had an unfavorable course: multiple myeloma, Waldenström's disease, and chronic lymphocytic leukemia. In myeloma, an increase in TTRS was observed when the bone marrow is invaded confirming the dominant local activity of an "osteoclast activating factor". TTRS is all the more extensive according to bone marrow invasion or in IgA or light chain myeloma, all of which are especially destructive of bone. It thus appears that determination of TTRS by bone histomorphometry is of diagnostic importance to recognize the benign or malignant nature of the disorder and has prognostic value in case of multiple myeloma. Bone histomorphometry thus appears as a useful tool in the thorough assessment of monoclonal gammopathies.

Biopsy↗
PubMed1986

[Prolonged survival in multiple myeloma. Characteristics of presentation and response to treatment of 73 patients who survived 5 years or longer].

Data concerning the presentation and response to treatment of 73 patients with multiple myeloma who survived for 5 years or more were reviewed. At the time of diagnosis, the proportion of patients with hypercalcaemia (4%), severe anaemia (9%), renal failure (10%) or high beta 2-microglobulin levels (25%) was low. Less than one-third of our patients belonged to a "high risk" group, as defined by the three classification systems adopted: the lowest percentage of such patients (18%) was observed with the Medical Research Council classification. In all patients, but even more in those with an initially aggressive disease (P less than 0.05), obtaining a plateau (70% of the cases) or even an optimal tumoral regression with complete disappearance of monoclonal immunoglobulin (26% of the cases) seems to be a highly favourable factor. The same applies, though to a lesser degree, to slow response to chemotherapy (18 months on average). In all responders whether the remission was maintained or not by chemotherapy seemed to have no influence on the frequency (70%) and delay of relapses (4 1/2 years on average from the time of diagnosis). The risk of secondary blood disease (2 AML 1, 1 AML4, 1 RAEB, 1 ASIA, four of which were directly responsible for death) after 4 years on average of chemotherapy must be taken into consideration.

Adult↗
PubMed1986

[Role of the assay of serum beta 2 microglobulin in the clinical evaluation of myeloma].

The survival of individual patients with multiple myeloma ranging from a few weeks to several years, careful pretreatment evaluation of prognostic factors is extremely important. Several methods of stratification are available, but in spite of their validity they present a number of problems, particularly with regard to their inter-reproducibility. In addition, they are of no help to evaluate response to chemotherapy, quality of remission, plateau phase or kinetics of relapse. Recent studies have clearly demonstrated that serum beta-2 microglobulin, as a single variable, is the best individual determinant as a prognostic marker in multiple myeloma. Using this assay and serum albumin as prognostic determinants, a simple stratification, superior to the three previously available methods, was developed. Serum beta-2 microglobulin is a very useful marker in the follow-up of most multiple myeloma patients. It appears to be a key measurement for assessing the prognosis and response to treatment of these patients.

Humans↗
PubMed1986

Importance of quantitative histology of bone changes in monoclonal gammopathy.

Quantitative histology of bone changes, using undecalcified transiliac bone biopsies (UTBB), was performed blindly in 46 individuals with monoclonal gammopathy (MG), including 17 with MG of undetermined significance (MGUS) and 29 with overt multiple myeloma (MM). Three MGUS presented an excess of osteoclastic resorption (OR) in the vicinity of clusters of tumour cells and developed overt B cell malignancies, chronic lymphocytic leukaemia, Waldenström's disease and MM respectively. On the other hand, MGUS with normal OR remained stable (median follow-up = 28 months), with one exception who developed a systemic amyloidosis. In MM, excessive OR was only observed in areas invaded by myeloma cells. OR was frequently normal in active MM lacking myeloma cells in UTBB. Active MM without lesions on radiography had excessive OR. IgA and pure Bence Jones MM appeared more osteoclastic than IgG cases (P less than 0.05). Of major interest was the finding that one third of MM presented histological bone changes similar to osteoporosis, osteosclerosis or osteoblastic metastasis. Two major findings must be emphasized from the current data: UTBB could be of major interest for the early detection of a B cell malignancy; heterogeneity of myeloma bone condition is unexpected. If some changes appear directly related to the tumour (i.e. excessive OR or osteoblastic dysfunction), some others are probably accidentally associated with it (i.e. osteoporosis), both needing treatment other than chemotherapy.

Aged↗
PubMed1986

Prognostic factors and staging in multiple myeloma: a reappraisal.

To assess the important factors in the prognosis and staging of multiple myeloma (MM), we have correlated the presenting clinical features of 147 previously untreated patients with MM with the survival duration using multiple regression analyses. We have included the three major available myeloma-staging systems (MSS), ie, Durie-Salmon (DS), Medical Research Council (MRC), and Merlini-Waldenström-Jayakar (MWJ), plus two new variables related to disease activity: the serum beta 2-microglobulin level (S beta 2M) and the instantaneous rate of bone resorption. Our study confirms the validity of the three MSS in the prediction of survival duration, with a slight but significant advantage for the DS MSS. Among single variables, S beta 2M was the most powerful indicator of prognosis (P less than .0001), serum albumin level being the only variable adding to this significantly (P = .02). Of major interest, S beta 2M alone was a better indicator than MRC and MWJMSS. Finally, S beta 2M and the serum albumin level, variables not included in the three MSS, were better indicators than the classical DS MSS and could be combined simply to give a very powerful system of stratification.

Calcium↗
PubMed1986

Production of interleukin 2 in multiple myeloma.

The production of interleukin 2 (IL-2) by peripheral blood mononuclear cells (PBMC) was studied in 15 normal controls (NC) and 29 patients with multiple myeloma (MM), including 19 patients with active disease (i.e. diagnosis, relapse) and 10 with inactive disease (i.e. complete remission and off-treatment plateau). IL-2 was produced after stimulation of PBMC with PHA alone or with PHA and PMA. The role of suppressor factors/cells on IL-2 production was evaluated using indomethacin and irradiation of PBMC. T cells and T cell subsets (i.e. helper/suppressor T cells) were defined using standard monoclonal antibodies (T3, T4, T8). The production of IL-2 in active MM was similar to that of NC, using either PHA or PHA and PMA. However, a constant defect of prostaglandin-mediated suppressor cells was observed in patients in plateau, with a significant increase of IL-2 production in comparison to that of NC or active MM. IL-2 is an essential factor involved in T cell proliferation. Recent data demonstrate that it plays a role in B cell proliferation and differentiation into antibody-secreting cells. Suppression of antibody synthesis is a major feature of active (but not inactive) MM. The fact that IL-2 production was not affected in MM, in spite of an imbalance of some T cell subsets, is of major interest.

Humans↗