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Biomedical subjects

X Mariette

Publications and source records attributed to X Mariette.

At least 73 records · Page 4Linked to original sources
PubMed1995

High-dose therapy and autologous blood stem cell transplantation in multiple myeloma: preliminary results of a randomized trial involving 167 patients.

Since 1986, we have treated young patients with aggressive multiple myeloma (MM) by high-dose chemotherapy (HDC) and total body irradiation (TBI) followed with autologous blood stem cell transplantation (ABSCT). To evaluate this strategy: 1) We conducted a phase II trial that included 63 patients. Within a median follow-up of five years after transplantation, overall survival was 60% and median event-free survival was four years, and 2) In the early 1990s, we initiated a prospective trial where, after collection of chemotherapy-mobilized ABSC, patients under 55 years of age with newly diagnosed MM were randomly assigned either to HDC and TBI supported with ABSCT (high-dose therapy [HDT] arm) or to a conventional vincristine, melphalan, cyclophosphamide and prednisone (VMCP) regimen (VMCP arm). In the latter, HDT with ABSCT was performed as a rescue therapy, in case of primary resistance to VMCP or at relapse in responders. As of June 1994, 167 patients have been enrolled since a median time of 26 months. Fourteen (8%) could not be randomized. Among the randomized patients (n = 153), 30 deaths were observed, 13 in the HDT group and 17 in the VMCP group (p = 0.28, two-sided log rank test). Overall survival rates at two years were estimated at 78% for all 167 patients, at 82% in the HDT group and at 67% in the VMCP group. ABSC, provided they are collected early in the disease course, allow a great majority of myeloma patients to receive HDT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Sjögren's syndrome and virus.

Though there have been claims for a key-role for a thus far unknown virus in the pathogenesis of Sjögren's syndrome (SS), conflicting results are to be discussed in this review. One candidate is Epstein-Barr virus which has been found within epithelial cells of labial salivary glands (LSG), using in situ hybridization and polymerase chain reaction. Hepatitis virus C has also been suspected, but an issue has to be made on serological false-positive results. In the light of the detection of the tax gene of human T lymphotropic virus type 1 in LSG, retroviruses have also been incriminated.

Hepacivirus↗
PubMed1994

[Sjögren's syndrome and virus].

Virus are suspected to play a role in triggering lymphoid proliferation observed in Sjögren's syndrome (SS). In this paper, attention is focused on the potential role of herpes virus, retrovirus and hepatitis C virus (HCV) in the pathogenesis of SS. Genes and proteins of Epstein-Barr virus (EBV) are detected in epithelial cells of salivary or lacrymal glands more often in SS patients than in controls. However, it could just be a consequence of the destruction of the glands by another mechanism. Endogenous retroviral sequences are detected with a high frequency in salivary glands of SS patients, than in controls. Sicca syndrome may occur in HIV, HTLV-I and HCV-infected patients. We found the expression of the tax gene of HTLV-I in epithelial cells of salivary glands from two patients without any evidence of HTLV-I-associated disease and without any seric anti-HTLV-I antibodies. Anti-SSA and anti-SSB antibodies are usually not detected in serum of patients with sicca syndrome occurring during evolution of recognized viral diseases. Thus, this kind of sicca syndrome could be a little different from classical auto-immune SS. However, it is tempting to consider oropharynx like a site of latency of a lot of virus which could infect salivary epithelial cells. In some people with a particular genetic background, this could lead to a lymphoid proliferation and, secondary, to the destruction of the glands.

Animals↗
PubMed1994

Monoclonal IgM from patients with peripheral demyelinating neuropathies cross-react with bacterial polypeptides.

Human monoclonal IgM associated with a demyelinating peripheral neuropathy often feature a distinct antibody activity directed against a glucuronyl sulphate epitope shared by myelin-associated glycoprotein (MAG), nerve glycolipids and low molecular weight peripheral nerve polypeptides. Earlier studies showed that these IgM use a diverse repertoire of VH and VL genes which exhibit somatic mutations, possibly indicative of an antigen-driven process. Here, we investigated whether such monoclonal IgM may react with environmental bacterial antigens. We found that six patients' sera and purified monoclonal IgM, as well as IgM from supernatants of three clonal anti-MAG-secreting cell lines reacted with unique 90-100 kD polypeptides from extracts of two out of 10 bacterial species. Purified MAG was able to inhibit this reactivity. These results indicate molecular mimicry as a possible mechanism of this immunomediated neuropathy and associated clonal lymphoid disease.

Antibodies, Bacterial↗
PubMed1994

Myeloma cell contamination of peripheral blood stem cell grafts in patients with multiple myeloma treated by high-dose therapy.

In order to assess the contamination with malignant cells of peripheral blood stem cell (PBSC) transplants used to support high-dose therapy in multiple myeloma (MM), we used the immunoglobulin heavy chain gene radioactive fingerprinting polymerase chain reaction (PCR) method to detect clonal cells in PBSC from 10 patients. The sensitivity of the technique allowed the detection of one clonal cell among 10(4) normal blood mononuclear cells. A clonal band was detected in 4 of 11 leukaphereses samples. The level of contamination was low because a clonal band could never be identified on ethidium bromide-stained agarose gels whose sensitivity is between 1 and 5%. The use of granulocyte-colony stimulatory factor (G-CSF) in combination with chemotherapy in three cases did not seem to increase the contamination of PBSC grafts; in one patient, G-CSF was used during a second course of leukapheresis which was free of detectable clonal cells whereas the first one performed after chemotherapy alone contained clonal cells. Thus, PBSC grafts may rarely be completely devoid of clonal potentially malignant cells but the level of contamination is much lower than in BM grafts. Whether graft contamination is an important adverse prognostic factor for patients with MM undergoing intensive treatment and autografting is still unsettled.

Antineoplastic Agents↗
PubMed1994

Autoantibodies sequencing may help to understand the physiopathology of some monoclonal lymphoid proliferations and autoimmune diseases.

Nucleotide sequences of variable regions of autoantibodies may help to understand the origin of B cells secreting autoantibodies, both in the context of monoclonal lymphoid proliferations and polyclonal autoimmune diseases. We established the nucleotide sequence of variable genes of four monoclonal IgM secreted by lymphoplasmacytic proliferations and directed to myelin-associated glycoprotein, of five anti-lamin B autoantibodies in patients with a lupus like vasculitis, and of one monoclonal IgM secreted in a chronic lymphocytic leukemia patient and directed to the cardiolipin/beta 2 glycoprotein I complex. A selection process (antigen-driven?) was probably implicated in the origin of autoantibodies in the first two situations although a random process occurred in the last one.

Antibodies, Monoclonal↗
PubMed1993

High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients.

Sixty-three patients with high tumor mass multiple myeloma were treated with high-dose chemotherapy and total body irradiation supported by autologous blood stem cell transplantation. After high-dose therapy, they were monitored for a median of 44 months. Seven patients died early from toxicity. All the other patients, including those whose disease was resistant to previous therapies, showed a tumor mass reduction. At 6 months postengraftment, 40 (71%) of the surviving patients had minimal residual disease and 11 (20%) were in apparent complete remission. During follow-up, 25 out of the 63 (39%) patients relapsed and 16 of these died; 31 (49%) had a sustained remission. The median overall and event-free survival times after transplantation were 59 and 43 months, respectively. The initial serum beta 2-microglobulin value (> or < 2.8 mg/L) and length of previous therapy (> or < 6 courses of chemotherapy) were the only significant prognostic factors. In all surviving patients, blood stem cell autograft provided satisfactory and sustained haematopoietic reconstitution most often within 15 days. High dose chemoradiotherapy followed by autologous blood stem cell transplantation is thus an important therapeutic option for young patients with aggressive multiple myeloma.

Adult↗
PubMed1993

[Antibody activities of monoclonal immunoglobulins].

Monoclonal immunoglobulins present a normal structure and have an antibody activity. This activity may be directed against exo-antigens especially bacterial, but more frequently against auto-antigens. It may then be symptomatic and therefore explain unusual clinical or biological manifestations in the course of monoclonal dysglobulinemias. The most common auto-antibody activities are directed against red blood cells (responsible for cold agglutinin disease), IgG (leading to the formation of cryoglobulinemia), and myelin (responsible for peripheral neuropathy). Often, the monoclonal auto-antibody activity is asymptomatic and polyspecific, as it is only the monoclonal expression of polyclonal natural auto-antibodies. Genetic study of variable segments of heavy and light chains used by these monoclonal antibodies are useful to precise the role played by antigen in the driving of the lymphoid proliferation. These physiopathologic models concerning monoclonal gammapathies are a useful tool to understand the physiopathology of polyclonal auto-immune disease and the role of auto-antibodies.

Antibodies, Monoclonal↗
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↗