Search PubMed⌕ Search

Biomedical subjects

B Dupont

Publications and source records attributed to B Dupont.

At least 235 records · Page 13Linked to original sources
PubMed1990

[Visceral candidiasis in 2 children treated for acute leukemia].

The authors report two cases of splenic and hepatosplenic candidiasis occurring during a protracted neutropenia induced by chemotherapy for acute leukemia (lymphoblastic and myeloblastic respectively). Fungal infection was revealed by persistent or recurrent fever after correction of neutropenia. Diagnosis was suggested by findings at abdominal ultrasonography. It was confirmed by histological analysis which, in the first case, required open liver biopsy. In both cases, lack of improvement of splenic lesions despite treatment with Amphotericin B followed by fluconazole led to splenectomy. Both patients received postoperative anti fungal therapy with Ampho B and at one year's follow up, the patient who had the hepatosplenic candidiasis seems to have recovered.

Adolescent↗
PubMed1989

Molecular analysis of the serologically defined HLA-Aw19 antigens. A genetically distinct family of HLA-A antigens comprising A29, A31, A32, and Aw33, but probably not A30.

The HLA-Aw19 complex consists of a number of serologically cross-reactive Ag (i.e., A29, A30, A31, A32, and Aw33) which exhibit an epitope shared by HLA-B and -C proteins. To investigate the structural basis for these serologic cross-reactivities, we have cloned and determined the nucleotide sequences for A30, A31, and Aw33, and compared the predicted amino acid sequences with those already available for A29, A32, and other class I allelic products. All alleles of the Aw19 group contained A-locus-specific sequences, exhibiting "A-ness." The structural similarities between Aw19 polypeptides were found in the alpha 1 and alpha 2 domains, where shared amino acid residues were identified that correlated with observed serological reactivity patterns. Seven Aw19-specific nucleotides were found. Two of these were silent substitutions, but the remaining five resulted in Aw19-specific amino acid residues. Each of the HLA-A alleles can be classified into one of the five serologically cross-reacting groups. In the Aw19 group, the alleles A29, A31, A32, and Aw33 are closely related serologically as well as genetically whereas A30 probably belongs to the A1/A3/A11 group. The similarity between A30 and the other Aw19 alleles may have resulted from two independent gene conversions affecting exons 2 and 3. Additional mutations or gene conversion-like events in A30 were also noted. It is postulated that gene conversions have played a significant role in the divergence of the Aw19 alleles. However, each serologically cross-reactive Aw19 allotype appears to have arisen directly from a common ancestral allele. A30 was the only exception, and this allele may represent an unusual allotype, which is subject to a high rate of genetic changes, as is seen in the H-2Kb gene of the mouse.

Alleles↗
PubMed1989

Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: II. In vitro analyses of host effector mechanisms.

To identify mechanisms potentially contributing to graft failure, 19 leukemic recipients of T-cell-depleted marrow transplants who failed to engraft following a transplant of HLA identical sibling marrow depleted of T cells by soybean agglutinin (SBA) and sheep erythrocytes (E) were evaluated. Peripheral blood mononuclear cells isolated at the time of failure were consistently of host origin, bearing the phenotype of suppressor T cells (CD3+, CD8+, Leu 7+). A direct cytolytic effect on 51Cr-labeled donor-derived target cells was not detected, a finding that contrasts with the donor-specific cytotoxic host T lymphocytes that have been regularly observed in patients rejecting HLA nonidentical SBA -E- BMTs. However, these host T cells did exhibit a strong and specific suppressive activity against the donor marrow CFU-GM in vitro. Furthermore, in contrast to prior findings in durably engrafted recipients of SBA -E- BMTs, the lymphocytes isolated prior to or at the time of graft failure lacked natural killer surface antigen expression and effector function.

Antigens, Surface↗
PubMed1989

[Treatment of mycoses and new antifungal agents].

The multiplication of iatrogenic factors, nosocomial diseases and acquired immunodeficiency syndrome is responsible for an ever increasing number of deep opportunistic mycoses, namely candidiasis, aspergillosis and cryptococcosis. The advent of a wide variety of rare opportunistic fungi is a fairly recent and worrying phenomenon. To combat these infections, often very serious, our therapeutic armentarium is rather scanty. Moreover, the prescription of the available drugs is limited by their toxicity, their spectrum and their route of administration or by the emergence under treatment of resistant mutants. Beside old products, such as amphotericin B and 5-fluorocytosine, miconazole and, mainly ketoconazole (both azole derivatives) were the first steps towards oral administration and low toxicity. Fluconazole is a triazole antifungal compound with a very original distribution to the meninges and urinary tract; it is mainly used in candidiasis and cryptococcosis. Another triazole compound, itraconazole, presents the particularity of being active against Aspergillus spp., Cryptococcus spp. and some agents of exotic mycoses. These two products are well tolerated and should soon be available for use in deep visceral mycoses. Other azole derivatives are under study. Among compounds issued from new chemical families, terbinafine (allylamine) is particularly active against dermatophytes, and cilofungine (a polypeptide) against fungi. These drugs are in the experimental stage. Research should be pursued aimed at developing, probably in new chemical families, and agent that is fungicidal in vivo.

Allylamine↗
PubMed1989

[Cryptococcosis].

Cryptococcus neoformans is a ubiquitous encapsulated yeast present in soil. The usual contamination is by the respiratory route with ensuing dissemination in predisposed patients. Acquired immunodeficiency syndrome is the leading predisposing factor and illustrates the role of cellular immunity. Corticosteroid therapy and diseases of the reticulo-endothelial system can also encourage the disease. The most common visceral localization is the central nervous system, with meningo-encephalitis. In AIDS and severely immunocompromised patients multivisceral dissemination may occur. The organism is detected by culture, smear and/or biopsy. The serological test with detection of the cryptococcal polysaccharide capsular antigen is of great help for the diagnosis. The discovery of four serotypes of C. neoformans and of biochemical differences between serotypes has increased our knowledge of the ecology and epidemiology of the organism. Serotype A strains are the most common in both natural and clinical isolates, serotypes B and C are more prevalent in clinical isolates in tropical countries; their ecological site in nature is unknown. The disease bears a poor prognosis, especially in the most immunocompromised patients. The standard treatment is a combination of amphotericin B and flucytosine, but it can be toxic to the bone marrow. Considerable interest has arisen in new potential anticryptococcal agents currently under experimental study, such as itraconazole and fluconazole.

Antifungal Agents↗
PubMed1989

[Histoplasmosis and other imported mycoses in 1989].

The most common systemic mycoses imported into France are the histoplasmosis caused by H. capsulatum, which comes from Black Africa and from the French overseas departments and territories (Guyane, Martinique, Guadeloupe, New Caledonia), and the histoplasmosis caused by the larger H. duboisii, which is exclusively Central African. In recent years, histoplasmosis has become an opportunistic infection in immunocompromised patients, particularly those with AIDS. Blastomycosis, imported from North America as well as from North Africa and Central Africa, and paracoccidioidomycosis, imported from Latin America, are pulmonary mycoses with cutaneous manifestations on the face and extremities and with various deep localizations which often follow a chronic course. Coccidioidomycosis, strictly limited to the desertic regions in the western part of the American continent, is also a pulmonary mycosis with multiple granulomas in the skin, bones, lymph nodes and meninges. Penicilliosis caused by Penicillium marneffei is a mycosis from South-East Asia which has recently been observed in European AIDS patients who had travelled in that part of the world.

Africa↗
PubMed1989

Isolation and expression of a cDNA clone encoding HLA-Cw6: unique characteristics of HLA-C encoded gene products.

The HLA-C encoded gene products display several characteristics which distinguish them from HLA-A and -B. The HLA-C antigens are poorly expressed on the cell surface, they display multiple proteins with different isoelectric points, and alloimmunization to HLA-C antigens is less common. To investigate whether the multiple products result from differential splicing of HLA-C gene transcripts, we have isolated a full-length cDNA clone encoding the Cw6 antigen. Class I antigens produced by the cDNA clone in transfected cells were of the same relative mass as those observed in the parental cells when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Isoelectric focusing (IEF) gel analysis of the cDNA translated products in transfectants revealed multiple IEF bands. All IEF bands detected in the transfectants were also found in the parental cells, indicating that the multiplicity of the C-locus products was not due to differential splicing of HLA-C gene transcripts, but was probably due to post-translational modification. Comparison of the sequences of C-locus alleles with those of A and B alleles did not show any apparent sequences which would generate multiple IEF bands. Comparison of the coding regions for seven HLA-C alleles and one HLA-C-related class I gene with available data for 15 HLA-A and 20 HLA-B alleles demonstrated several unique features for the HLA-C locus. Six sites in the extra cellular domains, three in a1 and three in a3, were unique. While the cytoplasmic (CP) domain of HLA-A and -B are almost identical, the CP of HLA-C alleles is unique. Similar unique features of HLA-C are also observed in the transmembrane domain, resulting in locus-specific residues between positions 295 and 300. The present study has ruled out differential mRNA splicing as a mechanism for the multiplicity of Cw6 antigens and demonstrated unique HLA-C locus sequences.

Amino Acid Sequence↗
PubMed1989

Molecular mapping of a new public HLA class I epitope shared by all HLA-B and HLA-C antigens and defined by a monoclonal antibody.

It has previously been shown that a mouse monoclonal antibody, designated 4E, reacts with an epitope common to all HLA-B and -C antigens and those of the HLA-Aw19 cross-reactive group, namely, HLA-A29, -A30, -A31, -A32, -Aw33, and -Aw74. In order to pinpoint the amino acid residues which comprise the public specificity recognized by 4E, and HLA-A29 cDNA clone was isolated and its predicted amino acid sequence compared with those of other cloned HLA class I genes. The isolated HLA-A29 cDNA corresponded to the rarer of the two A29 variant alleles, A29.1. Two amino acid residues of HLA-A29.1, gln-144 and arg-151, were found in all 24 HLA-B and HLA-C alleles examined but were present in only one of 15 HLA-A alleles for which sequence data are available. Importantly, this exceptional allele was HLA-A32, another member of the HLA-Aw19 cross-reactive group. Gln-144 and arg-151 should be capable of jointly contributing to the binding site for 4E, as they are situated in successive alpha-helical subregions and are predicted to be juxtaposed in the three-dimensional HLA molecule. Four other residues in the first or second external domains of HLA-A29.1 (thr-9, leu-62, gln-63, and his-102) were unique among the HLA-A alleles, but none of these was found in corresponding positions of HLA-B of -C alleles and thus failed to correlate with presence or absence of the 4E determinant. These observations are consistent with the notion that gln-144 and arg-151 define a determinant common to HLA-B, HLA-C, and the HLA-Aw19 cross-reactive group and the binding site of the monoclonal antibody 4E.

Amino Acid Sequence↗
PubMed1989

Loss of tolerance associated with disappearance of B cells in a patient sequentially transplanted with paternal and maternal bone marrow for the treatment of severe combined immunodeficiency disease.

We have studied the tolerance of engrafted T cells from a severe combined immunodeficiency disease patient sequentially transplanted with T-cell-depleted bone marrow from both HLA haploidentical parents. The T cells from this patient were shown by HLA typing and cytogenetic analysis to be of material origin (donor of the second graft) while HLA typing of peripheral E--populations and of an Epstein-Barr virus-transformed B-cell line established 2 1/2 years after transplantation revealed the presence of host, maternal, and paternal (donor of the first graft) HLA antigens. When tested at 30 and 60 months after the last transplant, engrafted T cells from this patient had only weak mixed lymphocyte culture reactivity to paternal cells which could be inhibited by monoclonal antibodies to HLA-DQ and DR but not by anti-DP. T cells obtained 60 months after transplant were stimulated with paternal cells in both bulk and limiting dilution cultures and failed to generate typical allocytotoxic cells to paternal T- or B-cell targets. Mixed lymphocyte cultures performed at 71 months revealed an increased proliferative response by patient cells to paternal antigens; however, the engrafted T cells remained tolerant to maternal and host antigens. Limiting dilution analysis performed at this time revealed the presence of cytolytic cells directed to paternal antigens. There were no detectable B cells (only identified source of paternal antigen) as measured by immunofluorescent analysis of peripheral blood, nor any evidence of B-cell function as assessed by in vitro assays (proliferation to staphylococcus aureus Cowen strain A and mitogen-stimulated immunoglobulin production) or in vivo production of serum immunoglobulin at 60 and 71 months. The appearance of alloreactivity associated with the loss of B cells in this patient further supports the conclusion that the maintenance of tolerance to major histocompatibility complex disparate cells requires the continued in vivo presence of cells bearing the tolerizing antigens.

Antibody Formation↗
PubMed1989

Characterization of B cells in severe combined immunodeficiency disease.

The circulating lymphoid cells of eight consecutive untreated infants with severe combined immunodeficiency disease (SCID) with B cells were analyzed for surface marker expression and function. The B cells of these children expressed sIg, HLA-DR, CD19 (B4), CD20 (B1), CD21 (B2), Leu-8, and lacked expression of CD10 (CALLA), as do normal peripheral blood B lymphocytes. SCID B cells also expressed antigens that are normally absent or present on only a minor subset of circulating adult B lymphocytes, including CD1c (M241), CD38 (OKT10), CD23 (PL13), with or without concomitant CD5 (Leu-1) expression. The B cells of these children were capable of proliferating in vitro when stimulated with Staphylococcus aureus Cowan I. However, in the presence of pokeweed mitogen, S. aureus Cowan I, and normal T cells, the sIg+ cells of these children produced only IgM. Studies performed on normal B cells obtained from cord blood, young children, and adults reveal that whereas cord blood B cells are predominantly CD1c, CD38, and CD23 positive, B-cell expression of these antigens decreases with age. Cord blood B cells, similar to SCID B cells, produce only IgM when stimulated in vitro with pokeweed mitogen and S. aureus Cowan I. Based on these observations, we hypothesize that SCID B cells represent a population of B cells present during normal B-cell ontogeny which becomes a minor subset when an individual develops full immunologic competence.

Antibodies, Monoclonal↗
PubMed1989

Genomic organization and chromosomal assignment for a serine protease gene (CSPB) expressed by human cytotoxic lymphocytes.

The human cytotoxic serine protease ("granzyme") B gene has been isolated and sequenced. The gene is approximately 3500 bp in length and consists of five exons and four intervening introns. Its organization therefore conforms closely to that of the previously cloned serine protease genes which are expressed in mouse cytotoxic lymphocytes and rat mast cells. The 5' upstream region is characterized by an atypical "TATA"-like transcriptional promoter and by a stretch of nucleotides bearing similarity to an enhancer core sequence believed to be requisite for the tissue-specific expression of serine protease genes in the exocrine pancreas. It has previously been demonstrated that mRNA transcripts from the human serine protease B gene are heterogeneous in size, due to frequent faulty intron/exon splicing. Two cryptic splice sites, which are used to generate these aberrant mRNA transcripts, have been identified. Using DNA blot analysis of a panel of human-rodent somatic cell lines, the human serine protease B gene has been localized to chromosome 14.

Amino Acid Sequence↗
PubMed1989

T cell depletion of human bone marrow. Comparison of Campath-1 plus complement, anti-T cell ricin A chain immunotoxin, and soybean agglutinin alone or in combination with sheep erythrocytes or immunomagnetic beads.

The aim of this study was to compare the extent of in vitro T cell depletion and recovery of hematopoietic progenitor cells achieved with five methods of T cell depletion. Bone marrow samples from the same source were treated with monoclonal antibody Campath-1 (CP1) and human complement, XomaZyme-H65 (anti-T cell ricin A chain immunotoxin), or soybean agglutinin (SBA) alone or in combination with sheep erythrocytes (EAET) or a cocktail of immunomagnetic beads (B) directly coated with anti-CD2, anti-CD3, or anti-CD8 monoclonal antibodies. Residual T cells were enumerated by limiting dilution analysis, EAET rosetting, and proliferative responses to phytohemagglutinin. The results of this study demonstrated the following reductions in BM T cells as detected by limiting dilution analysis (mean % control): SBA+B (99.9%), SBA+EAET (99.8%), CP1+C' (99.4%), anti-T cell ricin A chain immunotoxin (99.0%), and SBA alone (94.2%). Neither PHA response nor enumeration of residual EAET rosettes provided discriminating differences in the degree of T cell depletion by treatment method when T cell reductions exceeded 99.0% by LDA. These results demonstrate the ability of CP1+C', XomaZyme-H65, and SBA plus sheep erythrocyte or magnetic bead depletion to achieve a greater than 99% reduction of BM T cells and the importance of limiting dilution analysis in defining differences in T cell numbers when depletion exceeded 99%.

Animals↗
PubMed1989

Optimal conditions for in vitro T cell depletion of human bone marrow by Campath-1a plus complement as demonstrated by limiting dilution analysis.

Quantitations of residual T cells by limiting dilution analysis (LDA), immunofluorescence analysis, sheep red cell rosetting, and proliferative responses to phytohemagglutinin were done to identify treatment conditions that maximized the ex vivo T cell depletion (TCD) of human bone marrow (BM) with the rat monoclonal antibody Campath-1 (CP1) and complement (C'). Different treatment approaches achieved levels of TCD varying from 0.4 to 2.6 log10. However, under optimal treatment conditions, a mean (+/- SEM) log10 TCD of 2.60 +/- 0.12 was demonstrated by LDA. Concentrations of CP1 ranging from 5 micrograms to 300 micrograms/10(7) cells/ml achieved equally effective TCD as determined by LDA. An inverse relationship between the concentration of BM cells/ml and the extent of TCD was observed. Additional C' treatment did not increase TCD as detectable by LDA. Mean recoveries of CFU-GM (day 7), CFU-GM (day 14), CFU-GEMM, and BFU-E growth following CP1 + C' were 51, 43, 42, and 45% respectively. These results demonstrate the importance of cell concentration and treatment conditions for maximizing the depletion of BM T cells with CP1 + C'.

Animals↗
PubMed1988

A novel activation pathway for mature thymocytes. Costimulation of CD2 (T,p50) and CD28 (T,p44) induces autocrine interleukin 2/interleukin 2 receptor-mediated cell proliferation.

Prior studies have shown that thymocytes, unlike peripheral T cells, do not proliferate in response to mitogenic combinations of anti-CD2 mAbs. The present study demonstrated that stimulation by a mitogenic anti-CD2 combination (9-1 plus 9.6) with anti-CD28 induced vigorous thymocyte proliferation in the absence of exogenous IL-2. This thymocyte proliferation was IL-2 dependent as shown by the complete inhibition using anti-IL-2-R mAbs. Induction of IL-2-R transcripts was detected in thymocytes stimulated by the anti-CD2 antibody combination alone or the anti-CD2 combination plus anti-CD28 antibody. However, induction of IL-2 transcripts was observed only in thymocytes triggered jointly by the anti-CD2 combination plus anti-CD28 antibodies. The double-negative (CD4-8-) or CD1+ thymocytes isolated by sorting or by panning were unresponsive to CD2/CD28 triggering. The same mitogenic signal could induce vigorous proliferation of thymocytes with a mature phenotype, i.e., CD3+CD4+ or CD3+CD8+ thymocytes. Immunofluorescence studies demonstrated that the majority of CD3+ thymocytes were CD28+, and most of the CD28+ cells were located in the medullary compartment of thymus. These results indicated that the T cell lineage surface molecules CD28 and CD2 are involved in the regulation of expansion and further differentiation of mature thymocytes.

Antibodies, Monoclonal↗