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Biomedical subjects

J Bernard

Publications and source records attributed to J Bernard.

At least 109 records · Page 6Linked to original sources
PubMed1994

History of promyelocytic leukaemia.

The first reports on promyelocytic leukaemia came from Norway and France in 1957. Little by little, acute promyelocytic leukaemia acquired its rightful place in nosology as a hyperacute, invariable and rapidly fatal disease. In 1973, a high frequency of complete remissions induced by strong doses of daunorubicin and an acceptable frequency of true recovery, was demonstrated. After these preliminary events, the history of promyelocytic leukaemia was that of an important discovery: the first remissions of human acute leukaemia were obtained by cell differentiation, as all-trans retinoic acid induces complete remission of acute promyelocytic leukaemia in nearly all cases. The consequences of the discovery are discussed. For the long or middle term, we can hope for improved understanding of the action of retinoic acid, and possibly the preparation of new compounds with longer efficiency.

Daunorubicin↗
PubMed1994

Necrotaxis.

By the word necrotaxis is understood a collection of phenomena provoked by sudden cell death, or more exactly by the agony of a cell killed by the experimenter (Bessis, 1963). Recent work has followed three approaches: the role of the cytoplasm, and of anucleated fragments; the role of calcium; and the study of the direction or orientation of movement, by biophysical methods. Numerous questions remain unanswered: the presence or absence of relationship with immune phenomena and the comparison of necrotaxis and apoptosis.

Animals↗
PubMed1993

The phospholipase A2 inhibitor bromophenacyl bromide prevents the depolarization-induced increase in [3H]AMPA binding in rat brain synaptoneurosomes.

We previously demonstrated that potassium (KCl)-induced depolarization of synaptoneurosomes prepared from rat telencephalon increased [3H]amino-3-hydroxy-5-methylisoxazole-4-propionate ([3H]AMPA) binding to the AMPA receptor. In the present study, we determined the effects of inhibitors of various calcium-dependent enzymes on this response to depolarization. Treatment of intact synaptoneurosomes with the phospholipase A2 (PLA2) inhibitor, bromophenacyl bromide (BPB), produced a marked and dose-dependent reduction in KCl-induced enhancement in [3H]AMPA binding. BPB had no significant effect on [3H]TPP accumulation in intact synaptoneurosomes, an index of membrane depolarization. In contrast to BPB, inhibitors of calcium-dependent kinases and proteases did not reduced the KCl-induced increase in [3H]AMPA binding. The results strengthen the hypothesis that phospholipase-induced modifications of AMPA receptor properties may be an important component of synaptic plasticity.

Acetophenones↗
PubMed1993

Identification of CD4 and major histocompatibility complex functional peptide sites and their homology with oligopeptides from human immunodeficiency virus type 1 glycoprotein gp120: role in AIDS pathogenesis.

CD4 molecules interact with class II major histocompatibility complex molecules as a critical costimulatory signal in CD4+ cell immune activation. CD4 also recognizes a specific region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 forming a binding site for early stages of HIV-1 infection. We designed two software packages, AUTOMAT and CRITIC, which allowed us to identify similarities between regions of HIV-1 proteins and immunoregulatory protein sequences stored in data banks. In this report we have characterized (i) a pentapeptide, SLWDQ, found in both CD4 and HIV-1 gp120, which surprisingly had remained undetected in these two well-studied molecules until now, and (ii) an HLA sequence corresponding to the putative functional site of H2 I-A. We found that a region of gp120 (residues 254-263) known to be similar to a sequence in HLA class II beta chain overlaps this functional region. We showed experimentally that these two CD4 and HLA peptide segments inhibit CD4+ cell immune activation. There is strong inhibition (50% up to 80%) of immune activation by SLWDQ-containing gp120 segments and a lesser inhibition by the gp120 HLA-homologous segment. In addition, we found that SLWDQ induced in HIV-1-infected individuals a humoral (antibody) and cellular (cytotoxic T lymphocyte) immune reaction. We propose that these HIV-1 gp120 segments, together with the known CD4-binding region, may contribute to the HIV-1-induced immunosuppression by two mechanisms affecting CD4-HLA interaction during T-cell immune activation: autoimmune reaction toward CD4 and direct interference with the CD4-HLA costimulatory signal inducing CD4+ cell anergy with, as a consequence, generation of immunosuppression.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Ifosfamide-induced nonconvulsive status epilepticus.

We report the first case of nonconvulsive status epilepticus as a complication of chemotherapy with the nitrogen mustard derivative ifosfamide. Our patient developed encephalopathy, upper extremity myoclonus, and a periodic, triphasic electroencephalogic pattern that resolved acutely with intravenous diazepam treatment. Since significant morbidity and mortality is associated with unrecognized status epilepticus, electroencephalogic monitoring and a trial of diazepam is indicated in encephalopathic patients with rhythmic electroencephalogic patterns while receiving treatment with ifosfamide.

Brain↗
PubMed1993

Chronic effects of trimipramine, an antidepressant, on hippocampal synaptic plasticity.

The effects of trimipramine (TRIM), an antidepressant agent, on both the induction and the maintenance of long-term potentiation (LTP) was investigated in area CA1 of hippocampal slice preparations. Chronic administration (7-9 days) of TRIM in rat caused a large reduction in the magnitude of LTP induced by a theta burst stimulation (TBS) paradigm. Results indicate that the reduction of LTP produced by trimipramine does not seem to result from major changes in the physiological properties of the slice preparations. First, paired-pulse facilitation was not impaired following the drug administration suggesting that transmitter release was not modified in TRIM-treated slices. Second, the burst responses evoked by high-frequency stimulation exhibited the typical buildup of depolarization, which is due to both a reduction of IPSPs and the activation of NMDA receptors. Finally, the treatment did not change the amount of short-term potentiation induced by TBS nor did it modify the component of excitatory postsynaptic potentials (EPSPs) mediated by the activation of NMDA receptors, suggesting that the NMDA receptor functions remained intact in TRIM-treated slices. Taken together the present data suggest that the loss of LTP maintenance in TRIM-treated animals is more likely the result of the disruption by trimipramine of cellular processes that follow LTP induction. In addition, the results provide evidence for a possible correlation between the reduction in LTP expression and learning deficits produced by chronic administration of trimipramine.

Animals↗
PubMed1993

In utero acute graft-versus-host disease in a neonate with severe combined immunodeficiency.

We describe a male neonate with severe combined immunodeficiency who at birth had acute graft-versus-host disease (GVHD) as a result of maternal-fetal transfusion during pregnancy. Several clinical signs helped establish this diagnosis. Findings of a skin biopsy specimen confirmed the diagnosis of acute GVHD. Immunologic evaluation disclosed an absence of T and B lymphocytes. Acute GVHD in severe combined immunodeficiency most often occurs during the first weeks of life; intrauterine occurrence is unusual.

Biopsy↗
PubMed1993

HIV-1-induced immune suppression may result from autoimmune disorders including anti-SLWDQ autoantibodies.

We have previously unravelled the striking SLWDQ pentapeptide identity between HIV-1 env gp120 and the CD4 molecule. We show here that this pentapeptide is required for the functioning of the co-stimulatory MHC-CD4 signal in T4-cell activation since it suppresses antigen-induced T-cell proliferation. Moreover, concerning the MHC class II counterpart, the LNGQEETGVVSTN sequence which strongly inhibits T-cell immune activation is likely to be part of the functional site of the molecule. Interestingly the MHC/gp120 homology described by Young overlaps this MHC region. We further report that the gp120 SLWDQ peptide triggers an immune reaction which is both humoral (anti-SLWDQ antibodies) and cellular (CTLs against autologous targets carrying the pentapeptide) in HIV-1 infected individuals. Finally, anti-SLWDQ antibodies from patients sera purified by column chromatography strongly inhibit antigen-induced immune T-cell activation. This result led us to postulate that these antibodies found in high titers in HIV-1 infected individuals could contribute to set up the progressive systemic immune T-cell suppression characterizing AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

History of concepts and dogmas.

The history of 150 years of progression in our understanding of leukemia is the history of struggles against ignorance and struggles against dogma. Dogmas that have been subsequently refuted have existed in all aspects of research on leukemias: their classification, their evolution, and the requirements of successful therapy.

History, 19th Century↗
PubMed1993

History of promyelocytic leukemias.

History of a constant fight against dogmas, dogma refusing the promyelocyte existence, refusing acute promyelocyte leukemia existence, (first descriptions in Norway and in France in 1957), refusing remission, refusing complete cure (first complete cure with anthracyclins), accepting only destructive treatments. Franco-chinese works developed by Wang, Laurent Degos and their co-workers have proved the differentiation mechanism of remission due to the consequences of this important discovery. Acute promyelocytic leukemia, a model for other leukemias for cancers.

Animals↗