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Biomedical subjects

J C Brouet

Publications and source records attributed to J C Brouet.

At least 91 records · Page 5Linked to original sources
PubMed1992

Determination of the affinity of monoclonal human IgM for myelin-associated glycoprotein and sulfated glucuronic paragloboside.

We determined the association constant of eight monoclonal IgM with two of their targets, i.e. the myelin-associated glycoprotein (MAG) or the sulfated glucuronic paragloboside (SGPG). All IgM had a 10- to 100-fold higher affinity for MAG than for SGPG. The affinity of the different IgM for MAG ranged from 1.3 x 10(-6) to 7 x 10(-9) mol/liter. The Scatchard plots for MAG were curvilinear, half of the sites being of high or low affinity. In contrast, the plots were linear in the assay using SGPG. No obvious correlations were found between the fine specificity of these IgM for the glucuronyl sulfate epitope and their affinity, although most IgM with a high affinity reacted exclusively with SGPG derivatives retaining a sulfate group. There was no parallelism between the severity of the neuropathy and the affinity of the IgM for MAG or SGPG.

Globosides↗
PubMed1992

Severe hypoxemia-associated intrapulmonary shunt in a patient with chronic liver disease: improvement after medical treatment.

A 20-yr-old woman with chronic liver disease and angioimmunoblastic lymphadenopathy presented with marked hypoxemia caused by intrapulmonary shunt. Her respiratory tract showed her to be free of angioimmunoblastic lymphadenopathy manifestations. After 12 months of treatment with cyclophosphamide and corticosteroid, the immunologic disease disappeared. Unexpectedly, hypoxia-associated intrapulmonary shunt was no longer present either. To the best of our knowledge, this is the first case of dramatic improvement, with medical therapy, of severe hypoxemia related to noncirrhotic liver disease. However, the mechanism by which this treatment caused the regression of intrapulmonary shunt is unknown.

Adult↗
PubMed1992

The role of autologous blood stem cells in support of high-dose therapy for multiple myeloma.

During the last few years, high-dose therapy with hemopoietic stem cell support has become a well-admitted therapeutic option for young patients with MM. The role of allogeneic or autologous graft and of blood rather than bone marrow as the source of hemopoietic stem cells must be further investigated. Autologous PBSC transplantation has, however, both practical and theoretic advantages over allogeneic and autologous BMT: (1) It can be applied to most patients, especially if blood stem cells are collected early in the course of therapy. (2) It usually induces relatively rapid hematologic reconstitution. (3) In comparison with autologous BMT, it appears to minimize the hazard of the reinfusion of malignant cells.

Combined Modality Therapy↗
PubMed1992

Hodgkin's disease, clinical stages I, II A-B and IIIA. Results of brief chemotherapy followed by irradiation.

From October 1980 to September 1985, 152 patients with Hodgkin's disease (HD) in clinical stages (CS) I, II A-B and IIIA were treated with combined modality therapy (CMT): brief chemotherapy (CT) followed by radiotherapy (RT). CS IA and IIA cases received 3 cycles of MOP, while CS IB, IIB and IIIA cases were randomly assigned to receive MOP or MOP alternating with ABVD (4 cycles). Irradiation was delivered according to the areas initially involved and response to CT. CS I and II subjects in complete remission (CR) received localized fields, whereas CS I, II and IIIA subjects in partial remission (PR) received extended fields, with subtotal nodal RT for CS I and II and CS IIIA without pelvic involvement and total nodal RT for CS I and II below diaphragm and CS IIIA with pelvic involvement. Following CT, CR was 60% (IA-IIA: 71.5%, IB-IIB: 37%, IIIA: 55.5%), PR 35.5% and failure 4.5%. After CT and RT, CR was 98% (IA-IIA: 100%, IB-IIB: 95.5%, IIIA: 94.5%). Responses were similar using MOP and MOP/ABVD regimens. Fifteen patients relapsed (10%) and 15 died, 11 due to HD and 4 due to other causes, while after 7 years overall survival and relapse free survival were respectively 87% and 82% (IA-IIA 90% and 85%, IB-IIB: 80% and 80%, IIIA: 87% and 62%). Results were equivalent irrespective of CT regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[Diagnostic orientation in case of abnormal plasma immunoglobulins (excluding IgE)].

Serum immunoglobulins abnormalities may be qualitative or quantitative. So called benign IgG or IgA monoclonal gammopathy may be associated with certain rare clinical entities such as mucinar papulosis or leakage syndrom. Monoclonal IgM are mostly observed in patients with lymphoplasmacytic malignant proliferation; monoclonal IgM frequently posess a defined antibody activity which may be related to clinical symptoms such as hemolysis, cryoglobulinemic purpura or peripheral neuropathy. When a lymphoplasmacytic disease can be excluded, hypogammaglobulinemia is usually genetic, although rare causes of acquired hypogammaglobulinemia exist. Selective humoral deficiencies mostly of IgA or IgG2 may be missed on routine study of the serum. A marked hypergammaglobulinemia is observed in infectious or parasitic diseases, autoimmune disorders or certain lymphoid proliferation such as angioimmunoblastic lymphadenopathy. The presence of a monoclonal IsG or IsA morrate the need of a careful evaluation to second a malignand localized or gone marrow plasmacytic proliferation.

Agammaglobulinemia↗
PubMed1991

A human monoclonal IgG reactive with a private idiotope of a monoclonal IgM with autoantibody activity against myelin-associated glycoprotein.

One hundred and thirteen sera from patients with monoclonal IgG were tested for reactivity against a panel of 13 human monoclonal IgM having various autoantibody activities: 6 to myelin-associated glycoprotein (MAG), 2 to vimentin intermediate filament protein and 5 to red blood cell antigens [cold agglutinins with specificity directed to I antigen (3 cases), i antigen (1 case) or Pr antigen (1 case)]. One IgG was found to react with a monoclonal IgM with anti-MAG activity. This reactivity was characterized as idiotypic and directed against a private idiotope of the monoclonal IgM. This work provides further evidence for the existence of anti-idiotypic antibody activity of monoclonal Ig occurring in human B cell neoplasias.

Antibodies, Anti-Idiotypic↗
PubMed1991

Human autoantibodies to lamin B receptor are also anti-idiotypic to certain anti-lamin B antibodies.

Autoantibodies reactive with nuclear envelope proteins are mainly detected in human sera from patients with liver diseases. Some of these antibodies are directed to lamin B, lamins A and C, or to the lamin B receptor (LBR). We show here that the latter one are anti-idiotypic to certain anti-lamin B antibodies. Using an enzyme-linked immunosorbent assay specific for lamins we found that serum M containing anti-LBR antibodies inhibited the binding to lamins of anti-lamin B autoantibodies from three of five sera tested. Similar results were obtained using patient's M purified IgG. The binding of monoclonal IgM, lambda anti-lamin B antibodies produced by a lymphoblastoid cell line derived from the patient's blood lymphocytes was also inhibited. Absorption of serum M with nuclei abolished the inhibitory activity. No inhibition was recorded with normal sera or sera containing other antinuclear specificities. Anti-LBR antibodies did not alter the binding to lamins of sera containing anti-lamins A and C antibodies. Altogether these findings demonstrate that anti-LBR antibodies are also combining site related anti-idiotypic antibodies (Ab2) to certain anti-lamin B antibodies, provide further evidence for discrete specificities among anti-lamin B antibodies and suggest that the occurrence of autoantibodies to nuclear envelope antigens may be under idiotypic regulation.

Animals↗
PubMed1991

Interleukin-6 antisense oligonucleotides inhibit the growth of human myeloma cell lines.

IL-6 has been shown to be a plasmacytoma growth factor in mice and is believed to play a key role in the development of human multiple myeloma. We investigated the IL-6 requirements for the growth of two human myeloma cell lines, U 266 and RPMI 8226. These cell lines secreted minute amounts of IL-6 (20 U/ml) and featured IL-6 mRNA. IL-6 receptors were detectable at the surface of malignant cells by immunofluorescence. Antibodies to IL-6 did not alter the proliferation of these myeloma cells. There was a dose-dependent decrease, however, in [3H]-thymidine uptake in the presence of IL-6 antisense (and not sense) oligodeoxynucleotides; in the presence of 20 microM IL-6 antisense, an 80 and 95% inhibition of the proliferation of U 266 and RPMI 8226 cells was observed, respectively. These results provide strong evidence for an IL-6 autocrine proliferation of myeloma cells which may occur via internal interaction between IL-6 and the IL-6 receptor.

Base Sequence↗
PubMed1991

High dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma.

We report the results of peripheral blood stem cell (PBSC) collection performed after priming with a semi-intensive CHOP regimen in 70 patients with aggressive multiple myeloma (MM). Forty-one of the 44 previously untreated patients compared to 17 of the 26 patients with a refractory disease yielded stem cells enough for autotransplantation. Phenotypic and genotypic studies of collected mononuclear cells, even performed after depletion of monocytes and/or of T lymphocytes, did not reveal contamination by tumor plasma cells or clonal B cell precursors in any studied case. Forty-eight of the 58 patients with successful PBSC collection have been presently treated by high dose therapy followed by autologous blood stem cell transplantation (ABSCT). Among the 43 patients who received a regimen including total body irradiation, four died within six months after the autograft. All remainders responded and most often achieved an impressive tumor mass reduction. Ten relapsed and four died from disease progression. Nine to 70 months (median: 35 months) after blood stem cell collection, 29 patients are either in apparent complete remission or with a state of stable residual disease, most often minimal. Blood stem cell autograft was successful in all evaluable patients and the kinetic of hematologic recovery was roughly related to the amount of reinfused CFU-GM (2.1 to 50 x 10(4)/kg). Median delays for granulocytes greater than 500/mm3 and platelets greater than 25,000/mm3 were 15 days and 20 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[IL 6 and lymphoproliferative diseases].

Interleukin 6 has pleiotropic effects on cells from various lineages. Several data indicate that it may play a critical role in the development of multiple myeloma by an autocrine or paracrine stimulation pathway. For instance, we showed that oligodeoxynucleotides antisens of IL6 mRNA were capable to decrease the proliferation of two different myeloma cell lines. In Waldenström's macroglobulinemia, at the initial stage of the disease, there is an autocrine differentiation pathway which is dependant of the secretion of IL6 by tumor cells. IL6 may also be implicated in the pathogenesis of some other lymphoid malignancies such as follicular lymphomas or large cell lymphomas. Its role in the systemic symptoms of Castleman disease has been clearly established.

Cell Division↗
PubMed1991

IL6 and lymphoproliferative disorders.

Interleukin 6 has pleiotropic effects on cells from various lineages. Several data indicate that it may play a critical role in the development of multiple myeloma by an autocrine or parcrine stimulation pathway. For instance, we showed that oligodeoxynucleotides antisens of IL6 mRNA were capable to decrease the proliferation of two different myeloma cell lines. In Waldenström's macroglobulinemia, at the initial stage of the disease, there is an autocrine differentiation pathway which is dependent of the secretion of IL6 by tumor cells. IL6 may also be implicated in the pathogenesis of some other lymphoid malignancies such as follicular lymphomas or large cell lymphomas. Its role in the systemic symptoms of Castleman disease has been clearly established.

Castleman Disease↗
PubMed1991

Heterogeneity of the breakpoint localization in malignant cells with a 9p11 chromosomal abnormality.

The p11 band of the short arm of chromosome 9 is involved in various cytogenetic alterations occurring in several malignant diseases. Using probes isolated from the 9p11 band in the study of a case of alpha-heavy-chain disease (MAL) with t(9;14)(p11;q32), we studied the DNA from seven malignant cell samples, including four cases of acute lymphoblastic leukemia with tdic(9;12)(p11;p12). Using pulsed-field electrophoresis analysis we demonstrated that the breakpoints were 3-300 kb distant from the original MAL breakpoint without clustering within the subset of leukemias with the tdic(9;12).

Chromosome Aberrations↗
PubMed1991

Phenotype and immunoglobulin gene configuration of blood B cells from patients with multiple myeloma.

We have studied the phenotype and the immunoglobulin gene configuration of blood B cells from 15 patients with stage III multiple myeloma (MM) at diagnosis. Highly purified B cells (greater than 90% CD20 positive cells) were obtained after L-leucine methyl ester monocyte depletion and elimination of T cells by rosetting. The percentage of B cells with surface immunoglobulin (sIg) featuring the same light and heavy chain isotype as the serum monoclonal immunoglobulin was very low, except in one patient, in whom 25-30% of B cells displayed surface and cytoplasmic immunoglobulin (cIg) sharing idiotypic determinants with the serum monoclonal IgG kappa. In all cases but one the percentage of circulating plasma cells accounted for less than 2% of the enriched B cell preparations. In one patient purified B cell population contained 30% of plasma cells and the immunoglobulin gene study revealed a rearranged JH hybridizing fragment identical in bone marrow and blood B cell DNA samples. In the other 14 cases no rearranged fragment was detected although we used a technique allowing the detection of at least 2% clonal cells. The absence of clonal cells in the patient whose B cells contained a high percentage of cells featuring surface IgG molecules was confirmed on purified sIgG-positive cells. In addition CD20-positive cells from this patient did not contain gamma mRNA. Therefore the IgG molecules were clearly extrinsic. Although the existence of clonal B lymphocytes or of myeloma idiotype related B cells cannot be ruled out, they escape detection by sensitive genetic studies of immunoglobulin genes.

B-Lymphocytes↗
PubMed1990

Detection of Epstein-Barr virus in epidermal skin lesions of an immunocompromised patient.

Using in-situ hybridizaiton, we showed the presence of the Epstein-Barr (EB) virus genome in epidermal cells from a patient with chronic lymphocytic leukemia and unusual cutaneous lesions characterized clinically by a maculopapular eruption and histologically by epidermal cell degeneration and lymphoid cell infiltration. Such histologic changes are similar to those seen in graft-versus-host disease. The EB virus genome was mainly detected in the basal, germinative cells of the abnormal epithelium. Specimens of our patient's healthy skin were negative. The presence of EB virus DNA in skin lesions was confirmed by polymerase chain reaction adapted for analysis of paraffin-embedded tissue. These findings indicate that EB virus can infect the human epidermis and that the viral infection may produce a distinctive cutaneous disease.

Aged↗
PubMed1990

Altered signal transduction secondary to surface IgM cross-linking on B-chronic lymphocytic leukemia cells. Differential activation of the phosphatidylinositol-specific phospholipase C.

To further study the mechanisms by which surface Ig triggering activates the inositol phospholipid signaling pathway, we have used B cells from chronic lymphocytic leukemia patients which, as previously described, display two patterns of response upon sIg cross-linking: in one group this cross-linking induces an inositol phosphate release, an intracellular free Ca2+ concentration elevation and a subsequent cell proliferation; in a second group none of these events occur although there is an increased class II Ag expression following anti-mu stimulation as in the first group. We have been able to demonstrate that the phosphatidyl inositol specific phospholipase C (PI-PLC) can be activated in permeabilized B cells from the first group by direct stimulation, with GPT gamma S, of a guanine nucleotide binding (G) protein. In addition, since anti-mu + GTP gamma S stimulate an increased inositol phosphate production in these cells, this suggests that surface Ig cross-linking activates PI-PLC via a G protein. However, in cells from the second group no inositol phosphate is released after GTP gamma S stimulation although PI-PLC can be directly activated by high Ca2+ concentrations. This reflects in these cells, an interruption of the signaling cascade sIg/G protein/PI-PLC at the level of the G protein or at the G protein/PI-PLC coupling. In cells from both groups PMA treatment, which is known to alter phosphatidyl inositol metabolism in B cells, completely inhibits PI-PLC activation even by high Ca2+ concentrations. These studies show that the phosphatidyl inositol-dependent signaling cascade after surface Ig triggering can be altered at different levels in B cells.

B-Lymphocytes↗
PubMed1990

Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study.

Lymphoproliferative disease of granular lymphocytes (LDGL) is a recently recognized, relatively rare atypical lymphocytosis characterized by the presence of over 2000 lymphocytes with cytoplasmic azurophilic granules/mm3 in the peripheral blood. The clinical course is heterogeneous, varying from spontaneous regression to progressive, malignant disease. As a consequence, clinical intervention is not standardized. In a worldwide multicenter study, the authors observed 151 patients with LDGL for a mean follow-up time of 29 months. Forty-three patients were asymptomatic at the time of diagnosis. In the remaining cases, clinical symptoms included fever (41 cases), infections (58), neutropenia (47), anemia (17), and thrombocytopenia (12). In 69 cases, LDGL coexisted with an associated disease. Most patients had a nonprogressive clinical course despite the presence of severe symptoms. In 19 patients, death related to LDGL occurred within 48 months. The authors investigated which features at diagnosis were significantly associated with increased mortality. In the univariate analysis, lymph node and liver enlargement, fever at presentation, skin infiltration, a low (less than or equal to 5000/mm3) or high (greater than 20,000/mm3) peripheral leukocyte count, relatively low (less than or equal to 3000) or high (greater than 7000/mm3) absolute peripheral granular lymphocyte (GL) count, and a low (less than or equal to 15%) percentage of HNK-1-positive cells were found to be predictors of increased mortality. In the multivariate analysis, significant independent predictors were fever at diagnosis, a low (less than or equal to 15%) percentage of HNK-1-positive peripheral blood mononuclear cells (PBMC) and a relatively low (less than or equal to 3000) GL count. These results showed that about 25% of the patients with LDGL were diagnosed after a routine blood count and had no clinical symptoms. The remaining patients were symptomatic, with some experiencing a fatal clinical course. The author's analysis of the significant prognostic features of LDGL may help in understanding the heterogeneous nature of this syndrome.

Adolescent↗
PubMed1990

Differential effects of low and high concentrations of interleukin 6 on human B cells.

In this report we have studied the functional effects of a wide range of interleukin 6 concentrations on human B cells. B cells purified from tonsils and from five of six spleens proliferated directly in a dose-dependent manner in the presence of low concentrations (1-100 pg/ml) of IL 6 whereas B cells from the sixth spleen proliferated only after in vitro anti-mu antibodies activation. Only large B cells (presumably in vivo activated B cells) were responsive to IL 6. High concentrations of IL 6 (1-10 ng/ml) did not trigger B cell proliferation but were able to up-regulate the expression of the B5 activation antigen on B cells, whereas the expression of two other B cell antigens (CD20 and CD23) was unchanged. At all concentrations of IL 6 tested (0.01-10 ng/ml) no B cell differentiation occurred after 7 days culture. Depletion before culture of B5+ cells from the B cell-enriched spleen cell preparation abolished both the proliferative effect and up-regulation of B5 antigen induced by IL 6, indicating that this lymphokine acted primarily on activated B cells. This differential effect of "low" and "high" concentrations of IL 6 on activated B cells may solve controversy on the role of IL 6 as an early or late agent in B cell maturation.

Antigens, Differentiation, B-Lymphocyte↗