PubMed Health⌕ Search

Biomedical subjects

J C Brouet

Publications and source records attributed to J C Brouet.

At least 73 records · Page 4Linked to original sources
PubMed1993

[Treatment of multiple myeloma].

The various chemotherapeutic regimens in multiple myeloma allow only a mean survival of less than three years. Polychemotherapy has at best a minor advantage over monochemotherapy. High dose chemotherapy followed by hematopoietic stem cell grafts yields a notable percentage of apparent complete remission. The best therapeutic choices as well as the introduction of new drugs such as alpha interferon still needs prospective evaluation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Nucleotide sequence analysis of the VL and VH domains of five human IgM directed to lamin B. Evidence for an antigen-driven process in the generation of human autoantibodies to lamin B.

OBJECTIVE: To gain insight into the genetic origin of human antilamin autoantibodies, we determined the nucleotide sequence of the light and heavy chain variable region (VL and VH) domains of 5 IgM antibodies directed to lamin B. These antibodies represent a distinct subset of antinuclear antibodies, and their presence is associated with a particular lupus-like syndrome. METHODS: We derived and cloned lymphoblastoid cell lines from peripheral blood B cells of 3 patients, selected anti-lamin B-producing subclones, and sequenced the messenger RNA coding for Ig heavy and light chains. RESULTS: We isolated 2 subclones (1 IgM kappa, 1 IgM lambda) from one patient (FUR) and 2 subclones (both IgM lambda) from another (HER). In contrast, all 8 lines derived from B cells isolated from the third patient (BEN) synthesized identical anti-lamin B IgM kappa antibodies: All VL and VH domains from these 5 IgM were encoded by different VL or VH genes. DH regions were all different, and there was no restriction in the use of JL or JH segments. Analysis of the nucleotide sequence of the VL domains allowed the identification of the putative germinal gene in 3 instances (V kappa IV, Humkv325, and V lambda III.1); the overall ratios of replacement:silent mutations (R:S) were 6.5 and 1.2 in the complementarity-determining regions (CDRs) and framework regions (FRs), respectively. The 2 other lambda sequences belonged to the V lambda III family. With regard to VH domains, 3 of 5 derived from previously identified germline genes (VHIV 4.19, VHIV 4.22, and VHIII 9.1); the overall R:S ratio for these genes was 8 and 1.5 in CDRs and FRs, respectively. CONCLUSION: Taken together, these data provide evidence that the repertoire of human antilamin autoantibodies is not restricted and that the antigen (or another kind of selective pressure) plays a role in the generation of autoantibodies to lamin B. This hypothesis is in accordance with the reactivity of these antibodies to discrete epitopes of lamin B.

Antigens↗
PubMed1993

Detection of human T lymphotropic virus type I tax gene in salivary gland epithelium from two patients with Sjögren's syndrome.

OBJECTIVE: To investigate whether human T lymphotropic virus type I (HTLV-I) could be involved in the pathogenesis of Sjögren's syndrome (SS). METHODS: Labial salivary gland (LSG) biopsy specimens from 9 patients with SS (4 with primary SS and 5 with SS secondary to rheumatoid arthritis) and 9 controls were studied for the presence of the tax gene of HTLV-I using in situ hybridization, and for the presence of tax, gag, pol, and env genes of HTLV-I using the polymerase chain reaction (PCR). Testing for antibodies to HTLV-I and examination of lymphocytes on blood smears were performed to determine whether systemic viral infection was present. RESULTS: Using in situ hybridization and PCR, we detected the tax gene, but not the gag, pol, or env genes, of HTLV-I in LSG sections from 2 of 9 patients with SS and from none of the control subjects. Tax DNA was present mostly in nuclei of epithelial cells, but also in some lymphoid cells. Serum of the 2 affected patients did not contain antibodies to HTLV-I. In 1 patient, examination of blood smears revealed rare convoluted lymphocytes, sometimes with the appearance of "flower cells," as observed in the blood of HTLV-I-infected patients. CONCLUSION: None of the known endogenous retroviral sequences is homologous to the tax gene. Thus, we suggest that HTLV-I (or another related retrovirus) can infect salivary epithelium. Transactivation properties of the tax protein could be implicated in the pathogenesis of SS. Alternatively, viral infection could cause de novo expression of HLA-DR antigens and favor the presentation of antigens by epithelial cells, leading, in some genetically predetermined subjects, to lymphoid infiltration of the gland.

Antibodies, Viral↗
PubMed1993

Nucleotidic sequence analysis of the variable domains of four human monoclonal IgM with an antibody activity to myelin-associated glycoprotein.

We determined the nucleotide sequence of the VL and VH regions of four human monoclonal IgM directed to myelin-associated glycoprotein (MAG) and a nerve glycolipid, the sulfated glucuronic paragloboside (SGPG). Clonal lymphoblastoid cell lines (three cases) and an heterohybridoma (one case) secreting anti-MAG IgM were derived from patients' blood B cells. V kappa genes derived from the single germinal V kappa IV (two cases), the V kappa Id and the V kappa IIIa Humkv328h5 genes. VH genes derived from the VHIII 9.1 germinal gene (or a closely related gene) in two cases, whereas two others possibly represent new members of the VHIII or VHI variability subgroups. There was no obvious restriction in the use of J kappa, JH and DH segments. Somatic mutations were predominantly found in the CDR3 of the V kappa IV genes with an overall ratio of replacement over silent mutations of 7/0. The sequence of two VHIII genes exhibited five replacement mutations in CDR in comparison to that of the germ-line 9.1 gene. Although some V genes are likely to be overrepresented among anti-MAG IgM, the diversity of the immune repertoire for MAG and SGPG explains the lack of easily detectable public idiotopes among these IgM. This last finding, as well as a high ratio of replacement versus silent nucleotide mutations in the CDR of VL and probably VH genes, suggest that the pathogenesis of these monoclonal antibodies (and of the associated lymphoplasmocytic disorder) differs from that of other previously characterized monoclonal autoantibodies such as rheumatoid factors and cold agglutinins.

Amino Acid Sequence↗
PubMed1993

Expression of GpIb on plasma cells in a patient with monoclonal IgG and acquired von Willebrand disease.

To get insights into the pathogenesis of acquired von Willebrand disease associated with plasma cell dyscrasias, we searched for the expression of the physiological von Willebrand factor receptor, the GpIb/GpIX complex, on bone marrow plasma cells. The monoclonal spike in our patient corresponded to IgG kappa molecules; there was no plasma inhibitor to vWF:Ag or vWF:RiCoF. The bone marrow contained 1-2% plasma cells. Fresh bone marrow cells or plasma cells enriched bone marrow cells after a 48 h in vitro culture in the presence of interleukin 6 were stained by an immuno alkaline phosphatase technique using monoclonal antibodies (mAb) to von Willebrand factor, GpIb alpha and beta chain, GpIIb/IIIa and Gp IX. Two different mAb to GpIb alpha chains reacted with the majority (75%) of plasma cells whereas all other reagents yielded no staining. Malignant plasma cells from patients with multiple myeloma without haemostatic disorder were unreactive with anti-GpIb mAb. These data suggest that in some patients with acquired von Willebrand syndrome there is a GpIb mediated selective adsorption of von Willebrand factor on clonal plasma cells.

Aged↗
PubMed1993

Nodular lymphocyte predominance Hodgkin's disease featuring blood atypical polyclonal B-cell lymphocytosis.

The nodular lymphocyte predominance form of Hodgkin's disease (NLPHD) is considered as a B cell derived lymphoproliferative disease. A patient with NLPHD presented with an absolute increase in blood B cells with cytological features of mantle zone cells; these B cells were polyclonal, did not exhibit bcl-2 gene rearrangement, and some of them displayed non-clonal chromosomal aberrations. EB virus genome was not detected by Southern analysis. Thus, this study, taking advantage of the presence of an unusual population of blood atypical B cells, confirms data obtained on lymph nodes where, however, malignant cells may be scarce, indicating that NLPHD is a polyclonal B cell lympho-proliferative disease of mantle zone origin.

Adult↗
PubMed1993

Role of granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5 in the eosinophilia associated with T cell lymphoma.

We studied two patients with a leukaemic T cell lymphoma who presented with a marked increase in blood eosinophilia. To investigate the mechanism of the eosinophilia, supernatants of peripheral blood cells containing more than 80% lymphoma cells were tested by biological assays for the presence of colony stimulating factors (CSF). In one case supernatants stimulated the growth of granulocyte-macrophage (GM), erythroid and eosinophil colonies. These effects were neutralized by anti-GM-CSF antibodies; anti-IL5 antibodies slightly decreased eosinophil colony formation. Supernatants derived from the second patient cells stimulated the same lineages. Neutralizing experiments demonstrated that in addition to GM-CSF it contained interleukin 3 (IL-3) and interleukin 5 (IL-5). In agreement with the biological data, RNA studies using the polymerase chain reaction showed that cells from the first patient expressed GM-CSF transcripts; IL-5 transcripts were also detected in very low amounts. GM-CSF, IL-3 and IL-5 transcripts were detected in cells from the second patient. Thus eosinophilia associated with some T cell lymphoma is likely due to secretion of different combinations of cytokines by malignant cells.

Adult↗
PubMed1993

Characterization of a human monoclonal autoantibody directed to cardiolipin/beta 2 glycoprotein I produced by chronic lymphocytic leukaemia B cells.

We determined the specificity and sequence of immunoglobulin molecules synthesized by monoclonal B cells from a patient with chronic lymphocytic leukaemia (CLL) who presented with a number of clinical and biological autoimmune symptoms. Heterohybrids obtained by fusion of CLL cells with the mouse X63-Ag 8.653 myeloma produced IgM lambda MoAbs directed to the cardiolipin/beta 2 glycoprotein I (beta 2GPI) complex and ssDNA. They were devoid of polyreactivity. Nucleotide sequence analysis of the variable domain of the mu chain indicated the utilization of the VH4 71.2 gene or one allotypic variant, DXP4 and JH3 segments. The lambda light chain used the single gene from the V lambda 8 subfamily, J lambda 3 and C lambda 3 genes. The VH gene displayed 11 nucleotide changes in comparison with its putative germline counterpart. However, these nucleotide changes correspond to variations observed in other published VH4 sequences, suggesting gene polymorphism rather than somatic mutation. DXP4 and JH3 were also in germline configuration. The VL gene exhibited a single replacement mutation in CDR1. These data suggest that the monoclonal CLL B cells in this patient retained VH and VL genes in germline configuration although they secreted a pathogenic anti-cardiolipin antibody associated with clinical symptoms, vasculitis and thrombosis, which may be provoked by antibodies to the phospholipid/beta 2GPI complex.

Amino Acid Sequence↗
PubMed1993

[Immunoglobulins in hematology. Peripheral neuropathy associated with monoclonal IgM].

Peripheral neuropathy is often associated with a monoclonal IgM and occurs in about 3% of authentic Waldenström macroglobulinemias. In at least as many cases, the neuropathy is associated with a monoclonal IgM although lymphoplasmocyte proliferation is not detected, at least initially. In about 2/3 of the cases, the monoclonal IgM is a specific antibody against a myelin associated glycoprotein (MAG), two peripheral nerve glycolipids (SGPG and SGLPG), the peripheral nerve protein P0, other smaller molecular weight molecules of the peripheral nerves, or finally certain adhesion proteins such as N-CAM. All these IgM have a fine specificity against an epitope of the glucuronyl sulfate determinant present on the carbohydrate moiety of these proteins. The clinical manifestations are similar in all patients with sensorimotor polyneuropathy, with frequent sensory dominance and demyelinization. Atypical symptoms including motor dominance, paralysis of the cranial nerves, asymmetric forms, are rare. On histological examination, there is demyelinization and monoclonal IgM deposit along the nerve fibers. Passive in vivo and in vitro transfer experiences suggest that these monoclonal antibodies can play a role in triggering or maintaining the peripheral neuropathy. Despite identical or nearly identical antibody specificities of the monoclonal IgMs, the regions of the heavy or light chains involved vary from one patient to another, indicating that the glucoronyl sulfate determinant is quite variable. This variability is not found in other monoclonal autoantibody models with autoantibody activity such as the rheumatoid factor or cold agglutinins. These data would suggest the need for different therapeutic approaches using chemotherapy, plasmapheresis, high dose intravenous immunoglobulins and other immunomodulator treatments. Two therapeutic trials are discussed.

Antibodies, Monoclonal↗
PubMed1993

Lupoid sclerosis with antiphospholipid and antimyelin antibodies.

Lupoid sclerosis is a rare syndrome associating clinical symptoms of multiple sclerosis (MS), positive false tests for syphilis and positive tests for antinuclear and anticardiolipin antibodies. In a patient with lupoid sclerosis, antimyelin antibodies were detected by indirect immunofluorescence on human sciatic nerve sections. These antibodies were not found in the serum of control patients with MS nor in sera of patients with antiphospholipid autoantibodies and focal ischemic neurologic disease. The presence of such antimyelin antibodies may contribute to the underlying physiopathological mechanism of this syndrome.

Adult↗
PubMed1992

H chain V region sequences of three human monoclonal IgM with anti-myelin-associated glycoprotein activity.

The amino acid sequence corresponding to the V region H chain gene used by three monoclonal IgM directed to the myelin-associated glycoprotein (MAG) is presented. They all belonged to the VHIII variability subgroup, but each may well represent a new member of this family inasmuch as their homology with previously sequenced VHIII genes was less than 80%. Strikingly, there was no greater homology between the H chain V regions of the anti-MAG IgM. Partial amino acid sequence data indicated that these V regions were joined to as yet unidentified DH segments; however, two H chains used very similar DH, possibly indicating that this sequence was involved in the fine specificity of the IgM for MAG. All H chains included a JHIV region. These data, together with results obtained from the sequence of the three kappa L chains of the same IgM molecules (Mihaesco, E., H. Ayadi, N. Congy, M. C. Gendron, J. P. Roy, H. Heyermann, B. Frangione, and J. C. Brouet. 1989. J. Biol. Chem. 264:21481), indicate that the repertoire of VL and VH gene segments used by anti-MAG IgM is quite diverse, in contrast to previous structural data obtained for other human monoclonal IgM autoantibodies. Possibly, these differences reflect distinct pathogenesis.

Amino Acid Sequence↗
PubMed1992

Characterization of two human monoclonal IgM antibodies that recognize nuclear lamins.

Using immunofluorescence and immunoblotting techniques, we have identified monoclonal IgM lambda from two patients that are specific for lamins A and C and lamin B, respectively. Lamins A, B, and C are peripheral membrane proteins of the nuclear envelope with structural similarities to cytoplasmic intermediate filament proteins. When studied by indirect immunofluorescence on rat tissues, the serum containing anti-lamin B IgM stained smooth and striated muscles in addition to nuclear envelopes. Lamin B antibodies affinity purified from this serum were able to label muscle cells, suggesting that lamin B shares an epitope(s) with an unidentified muscular component(s). Since in an enzyme-linked immunosorbent assay there was no reactivity with a panel of proteins which are frequent targets of "natural" antibodies, these monoclonal IgM appear to belong to the rare category of IgM that possess a restricted specificity.

Animals↗
PubMed1992

An anti-B cell autoantibody from Wiskott-Aldrich syndrome which recognizes i blood group specificity on normal human B cells.

We previously identified IgM autoantibodies in the sera of patients with Wiskott-Aldrich syndrome (WAS) that react with a subset of normal human B lymphocytes and induce B cell differentiation in vitro. From splenocytes of a patient with WAS we generated heterohybridomas (HY18 and HY21) and a lymphoblastoid cell line (LWA10) that produce human IgM lambda or IgM kappa anti-B lymphocyte autoantibodies, respectively. Immunohistochemical and multiparameter flow cytometric analyses demonstrate that these autoantibodies are specific for lymphocytes of the B lineage and preferentially stain B cells that reside in the mantle zone of secondary follicles and that constitutively co-express the CD5 surface antigen and most major autoantibody-associated cross-reactive idiotypes; in addition, these antibodies stain most pre-B cells in adult bone marrow. Molecular studies show that these anti-B lymphocyte autoantibodies are encoded by a highly conserved VH4 gene, designated VH4.21. The gene encodes a number of autoantibodies, especially anti-i and anti-I IgM cold agglutinins. Hemagglutination and surface labeling studies reveal that HY18 and LWA10 recognize the "i" carbohydrate antigenic determinant(s) which is classically found on human cord red blood cells and, as shown now by this study, on a subpopulation of human B cells which expresses it early in B cell development. These studies raise the possibility that the gene product encoded by this highly conserved germ-line VH4 gene may play a physiological role in B cell development and/or differentiation.

Amino Acid Sequence↗
PubMed1992

Alpha heavy chain disease alpha mRNA contain nucleotide sequences of unknown origins.

Human alpha heavy chain disease is characterized by the production of abnormally short alpha IgH chains. In previously published cases it has been found that the malignant cells produce abnormal alpha mRNA, lacking VH and CH1 sequences and composed of a leader sequence peptide, sequences of variable length (69 to 84 bp) and of unknown origin, followed by normal CH2 and CH3 sequences. In this study we established the nucleotide sequence of alpha mRNA for six cases of alpha heavy chain disease. We observed that all six alpha mRNA lack the VH and CH1 sequences as do those previously described. They also contain in-frame inserts of unknown origin between the leader peptide and the normal CH2 and CH3 coding sequences. These inserts are of variable length (42 to 105 bp) and they are unrelated. These results suggest the existence of a common mechanism defect leading to deletions/insertions in alpha heavy chain disease rather than a specific interaction between alpha 1 IgH gene with a unique defined molecular species.

Amino Acid Sequence↗
PubMed1992

A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T cell lymphoma.

A t(4;16)(q26;p13.1) chromosome translocation found in tumour cells from a patient with a T cell lymphoma was shown to rearrange the interleukin 2 gene, normally located on chromosome band 4q26, with sequences from chromosome band 16p13.1. A cDNA library of tumour cells was screened with an interleukin 2 gene-specific probe. Three clones were isolated, which consisted, from 5' to 3', of the three first exons of the interleukin 2 gene followed by a 16p13 in-frame sequence encoding 181 amino acids. A probe derived from this sequence detected a 1.2 kb transcript in various cell lines exhibiting mature B lymphoid cell features, but this was not detected in other cell lines representative of other haematopoietic lineages, or in other organs. For this reason, the novel gene was termed BCM for B cell maturation. The open reading frame of BCM normal cDNA predicted a 184 amino acid protein with a single transmembrane domain which had no homology with any protein sequence stored in data banks. Our data indicate that BCM is a new gene whose expression coincides with B cell terminal maturation.

Amino Acid Sequence↗
PubMed1992

Bone densitometry in patients with multiple myeloma.

PURPOSE, PATIENTS, AND METHODS: We performed dual-energy x-ray absorptiometry in 10 selected patients with aggressive multiple myeloma in whom substantial tumor mass reduction was achieved after high-dose chemoradiotherapy followed by autologous blood stem cell transplantation. RESULTS: In most cases, bone mineral density (BMD) of the spine was initially low (Mean Z score: -2.69, SEM 0.76) and dramatically increased after treatment (mean increase 16.4%; 7.7% with 95% confidence interval 2.2 to 12.2, excluding one patient whose spine BMD increased by 94.8%). In contrast, skeletal roentgenograms, computed tomographic scans, and magnetic resonance imaging did not reveal any significant improvement of patients' bone lesions. CONCLUSIONS: In patients with multiple myeloma, bone densitometry could be a useful way to assess the efficacy of treatment on bone status.

Absorptiometry, Photon↗