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Biomedical subjects

C Favre

Publications and source records attributed to C Favre.

At least 19 recordsLinked to original sources
PubMed1994

Continuity and discontinuity of psychopathology: a study of patients examined as children and as adults. III--The infancy of "adult personality disorders".

We undertook a prospective study of all the children who, having consulted the Child Psychiatry Services (Service Médico-Pédagogique) between 1963 and 1967, later consulted the Adult Public Psychiatry Service (720 cases). We looked for specific clinical clusters which would enable us to differentiate statistically the groups of children according to their adult diagnoses. We present here the results for the group of children who were diagnosed as suffering from "personality disorders" in adulthood. We were able to establish an infantile cluster that significantly differentiated these children. It includes: aggressiveness, oppositional behaviour, unsociability, conflicts with peers. 54.6% had already been diagnosed as suffering from personality disorders in childhood. According to these results, the more a consulting child fits this profile, the greater the risk that he will suffer from a "personality disorder" in adulthood. We discuss the continuity/discontinuity of the symptomatology, and the implications for diagnoses of "personality disorders" and "borderline personalities".

Adolescent↗
PubMed1992

Purification of an inositol 1,4,5-trisphosphate-binding calreticulin-containing intracellular compartment of HL-60 cells.

To investigate the identity of Ins(1,4,5)P3-sensitive intracellular Ca2+ stores in myeloid cells, we have developed a method that yields subcellular fractions highly enriched in Ins(1,4,5)P3 binding. HL-60 cells were disrupted by nitrogen cavitation, and subcellular fractions were obtained by differential centrifugation, followed by Percoll- and sucrose-density-gradient separations. A subcellular fraction enriched 26-fold in Ins(1,4,5)P3-binding sites was obtained. This fraction showed no enrichment in plasma-membrane markers and only a comparatively moderate enrichment (7-fold) in endoplasmic-reticulum markers. The ratio between specific enrichment of Ins(1,4,5)P3 binding and endoplasmic-reticulum markers in the different fractions varied over 50-fold, from less than 0.1 to greater than 5. The purified Ins(1,4,5)P3-binding fraction was enriched to a similar extent (27-fold) in the putative intravesicular Ca(2+)-storage protein calreticulin. Our results favour the concept of a distinct Ins(1,4,5)P3-binding, calreticulin-containing compartment (i.e. the calciosome) in HL-60 cells.

Calcium-Binding Proteins↗
PubMed1992

[Anterior ischemia of the optic nerve and anemic retinopathy].

We report on the case of a 59-year-old man with the association of an anterior ischemic optic neuropathy on the left eye and a bilateral anemic retinopathy following an extreme and prolonged post-operative anemia, because the patient had refused blood-transfusion. After one year of follow-up, the visual acuity did improve on the left eye. This association is rare, and only few cases have been reported.

Anemia↗
PubMed1992

The immunophenotype in infant acute lymphoblastic leukaemia: correlation with clinical outcome. An Italian multicentre study (AIEOP).

A detailed analysis of immunophenotype of 112 infants aged less than 18 months with acute lymphoblastic leukaemia (ALL) was performed. Patients were divided into three groups on the basis of age at presentation (under 6 months: group 1: 6-12 months: group 2; 13-18 months: group 3). There were three cases of T-ALL (2.6%). The proportion of other subtypes was: common ALL in 59 patients (52.68%), pre-B ALL in 15 patients (13.3%), pre-pre-B ALL in 27 (24.1%) and acute undifferentiated leukaemia (AUL) in eight patients (7.14%). In non-T ALL, positivity to CD10 (corresponding to C-ALL and pre-B ALL) was distributed in the three age groups as follows: 38.88% (group I) 65.38% (group II) and 86.36% (group III). Conversely, immature phenotypes (pre-pre-B and AUL) were found more often in the younger patients of groups I and II, as well as anomalous phenotypes, such as the presence of myeloid antigens (MyAg) and of CD7. Prognostic significance was evaluated as event-free survival (EFS) by statistical analysis. A better outcome in CD10-positive ALL than in CD10-negative ones (48% v. 25% of long-term survivors) was demonstrated in all infants. Similarly, EFS was significantly better in MyAg-negative than in MyAg-positive cases. These results were confirmed also when adjusting for white blood cell count. This allowed the identification of CD10-negative, MyAg-positive ALL, which were relatively more frequent in infants and had a poorer clinical outcome with the current therapies. This study stresses the prognostic relevance of the immunological study in infant leukaemias and its utility in choosing different therapeutic modalities for poor risk phenotypes.

Antigens, CD↗
PubMed1992

[Continuity and discontinuity of psychopathology: a study of patients examined as children and as adults. I. Antecedents of adult schizophrenic disorders].

The demographical stability of the Canton of Geneva made it possible for us to do a prospective study of all the children who had consulted the Child Psychiatry Service between 1963 and 1967 and who later consulted the public adult psychiatry services. On the basis of the adult diagnoses, wo looked for specific clinical "clusters" in childhood which would allow us to differentiate statistically the groups of children. We present here the results of the group of children who developed schizophrenia in adulthood. We found a specific childhood "cluster" which clearly distinguishes these children from the others. It includes: serious relational disorders, neurodevelopmental impairment, attention deficit and school learning disorders.

Adolescent↗
PubMed1992

Distribution of surface-membrane molecules on bone marrow and cord blood CD34+ hematopoietic cells.

We have investigated the distribution of membrane molecules on CD34+ hematopoietic cells isolated from human bone marrow (BM) and cord blood (CB). A distinct CD10+ population was present in BM, but it was not detected in CB. Most CD34+ CD10+ cells in BM were B-cell precursors (BCP), because they expressed CD19. However, CD40 and CD37 were found on the majority of CD34+ cells from either BM or CB, demonstrating that these antigens are not restricted to B-lineage CD34+ cells. CD40 and CD37 were lost during culture of CD34+ cells in the presence of interleukin 3 (IL-3), indicating transient expression early in myeloid development. CD13 antigen was detected on virtually all CD34+ cells from BM and CB. Accordingly, CD13 was present on CD34+ CD10+ cells, demonstrating that this structure is not restricted to myeloid CD34+ cells. In contrast, myeloid CD33 antigen was not detected on CD34+ CD10+ cells. Expression levels of CD13 and of CD33 were heterogeneous in BM, reflecting diversity within the resident CD34+ population. CD25 and CD71 were found on a proportion of CD34+ cells from either BM or CB and maintained during culture in IL-3, consistent with a distribution on activated cells. Finally, a variety of adhesion receptors were present on CD34+ cells. These included the alpha 4 beta 1 (VLA-4), alpha 5 beta 1 (VLA-5), and alpha L beta 2 (LFA-1) integrins, as well as ICAM-1, LFA-3, H-CAM, and LAM-1. Expression of adhesion receptors was remarkably similar in BM and CB, and it followed an all-or-nothing pattern that failed to delineate CD34+ subsets. Taken together, our data show that although CD34+ cells from BM constitute a more heterogeneous population, resident and circulating CD34+ cells largely display the same cell-surface molecules.

Antigens, CD↗
PubMed1991

Potentiation of early hematopoiesis by tumor necrosis factor-alpha is followed by inhibition of granulopoietic differentiation and proliferation.

We have previously shown that tumor necrosis factor-alpha (TNF alpha) strongly potentiates interleukin-3 (IL-3)-induced short-term proliferation of human CD34+ hematopoietic progenitor cells (HPC). Using longer term cultures of CD34+ HPC, we demonstrate here that this initial potentiation ceases after 10 to 12 days; whereupon TNF alpha displays inhibitory effects. Thus, TNF alpha was found to inhibit cells of granulocytic affiliation while it potentiates the development of maturing cells of the monocytic lineage both in liquid and semi-solid (day 14 colony-forming unit) cultures. TNF alpha was demonstrated to reversibly block granulocytic differentiation at the level of uncommitted CD13-, CD15- blast cells that accumulate in IL-3 + TNF alpha cultures. Furthermore, growth of committed granulocytes (CD15+) from IL-3 cultures was also inhibited by TNF alpha through an arrest of cell cycle in G0/G1. Finally, the use of neutralizing anti-TNF alpha monoclonal antibody and limiting dilution studies indicate that the inhibitory effects of TNF alpha are direct. Taken together, our data demonstrate that, following a phase of potentiation of proliferation of early HPC, TNF alpha displays direct inhibitory effects due to negative interference with both granulocytic differentiation and proliferation of granulocytic cells.

Antibodies, Monoclonal↗
PubMed1991

Micronuclei in lymphocytes of young patients under antileukemic therapy.

The micronucleus test in peripheral blood lymphocytes was employed in the cytogenetic monitoring of children with acute lymphocytic leukemia (ALL), who had undergone chemotherapy and radiotherapy. Patients were treated with a variety of drugs, which included vincristine, methotrexate, daunomycin and prednisone; they also underwent cranial irradiation at the end of the first intensive phase of therapy. The first group under study consisted of 15 subjects on therapy, who showed a marked increase in micronucleated lymphocytes (mean: 19.96 +/- 12.96%) as a consequence of treatment compared with the control group (mean: 3.67 +/- 1.55%), while lower average values were obtained from 15 other subjects at the end of treatment (mean: 13.16 +/- 8.44%). A group of 6 patients was monitored during the entire period of therapy, namely at diagnosis, after 3 months of therapy, throughout maintenance therapy and at the end of it. The whole treatment lasted about 2 years. The results revealed a marked increase in basal micronucleus frequency, due to therapy: the micronucleated lymphocyte frequency remained significantly high throughout the treatment for almost all patients. These data clearly suggest the validity of the methodology in pointing out the role played by antileukemic agents in inducing somatic genetic damage.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Tumor necrosis factor-alpha strongly potentiates interleukin-3 and granulocyte-macrophage colony-stimulating factor-induced proliferation of human CD34+ hematopoietic progenitor cells.

Previous studies have shown that tumor necrosis factors (TNFs) inhibit the proliferative effects of crude or purified colony-stimulating factors (CSFs) on low density human bone marrow cell fractions. In the present study we investigated the effects of TNF alpha on the growth of highly purified CD34+ human hematopoietic progenitor cells (HPC) in response to recombinant CSFs. In short-term liquid cultures (5 to 8 days), TNF alpha strongly potentiates interleukin-3 (IL-3) and granulocyte-macrophage-CSF (GM-CSF)-induced growth of CD34+ HPC, while it has no proliferative effect per se. Within 8 days, the number of viable cells obtained in TNF alpha-supplemented cultures is threefold higher than in cultures carried out with IL-3 or GM-CSF alone. Secondary liquid cultures showed that the potentiating effect of TNF alpha on IL-3-induced proliferation of CD34+ HPC does not result from an IL-3-dependent generation of TNF alpha responsive cells. Limiting dilution analysis indicates that TNF alpha increases both the frequency of IL-3 responding cells and the average size of the IL-3-dependent clones. The potentiating effect of TNF alpha on IL-3- and GM-CSF-dependent growth of CD34+ HPC is also observed in day 7 colony assays. Under these short-term culture conditions, TNF alpha does not appear to accelerate cell maturation as a precursor morphology is retained. Finally, TNF alpha inhibits the relatively weak growth-promoting effect of granulocyte-CSF (G-CSF), which acts on a more committed subpopulation of CD34+ HPC different from that recruited by IL-3 and GM-CSF. TNF beta displays the same modulatory effects as TNF alpha. Thus, TNFs appear to enhance the early stages of myelopoiesis.

Antigens, CD↗
PubMed1990

Interleukin-4 has basophilic and eosinophilic cell growth-promoting activity on cord blood cells.

Effects of human recombinant interleukin-4 (IL-4) on cord blood cells depleted of T cells and monocytes were tested in colony assays and liquid cultures. IL-4 did not induce colony formation in semisolid medium, but enhanced generation of basophil colonies induced by conditioned medium (CM) of the bladder carcinoma cell line 5637. In liquid cultures, variable degrees of basophil growth were observed in the presence of IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, and 5637 CM, or even with IL-4 alone, but the highest number of basophils were obtained when IL-4 was used in combination with IL-3 or 5637 CM. Progressive basophil growth was observed during 3 to 4 weeks of culturing, whereafter the numbers of basophils remained stationary for another 3 weeks. Interestingly, cord blood cell cultures performed with IL-3 contained variable percentages of eosinophils that were further enhanced in the presence of combinations of IL-3 and IL-4. These latter cultures contained approximately 50% eosinophils and 50% basophils. Kinetic studies indicated that basophils were present 7 days after onset of the cultures, whereas eosinophils did not appear before day 13. In contrast to the pronounced effects of IL-4 and 5637 CM on basophil development, relatively low numbers of eosinophils were observed under these culture conditions. Our results indicate that eosinophil and basophil development are regulated by different sets of factors, and that IL-4 has an enhancing effect of both cell lineages in association with the appropriate factors.

Basophils↗
PubMed1989

Epitope mapping of recombinant human gamma interferon using monoclonal antibodies.

Five monoclonal antibodies (MAbs B22, B27, 3-6, 32 and 35) specific for human recombinant IFN-gamma were characterized. These MAbs were used to set up quantitative sandwich ELISAs which allowed the detection of 1.25 ng/ml of IFN-gamma when diluted in normal human serum. Epitope mapping of the IFN-gamma molecule using these MAbs demonstrated that antibodies 3-6 and 32 which did not inhibit the biological activity of IFN-gamma recognized an epitope localized on the 15 C-terminal amino acids, suggesting that this portion of the molecule was not implicated in the biological activity of IFN-gamma. Sandwich ELISAs were performed using various pairs of MAbs. The level of reactivity obtained when antibodies B22 and B27 were used simultaneously as catcher and tracer was similar to the result obtained with two antibodies recognizing different epitopes. These results confirm that the IFN-gamma molecule is a dimer in solution and indicate that the two sites of the IFN-gamma dimeric molecule which are associated with the biological activity (epitope B22/B27) are fully exposed. In contrast, the C-terminus is only partially accessible to the antibodies 3-6/32, suggesting that the dimerization of IFN-gamma molecule results in the interaction of regions of the monomers that are homologous and adjacent to the C-terminus.

Antibodies, Monoclonal↗
PubMed1989

Combined and sequential effects of human IL-3 and GM-CSF on the proliferation of CD34+ hematopoietic cells from cord blood.

The proliferative effects of recombinant human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated in semi-solid and liquid cultures of purified CD34+ hematopoietic cells obtained from umbilical cord blood. No important differences in overall cloning efficiencies in response to IL-3 or GM-CSF were observed in semi-solid medium in the presence of erythropoietin (Ep). However, GM-CSF was less effective for the development of erythroid bursts (BFU-E), and only IL-3 was observed to induce significant numbers of mixed-erythroid colonies (E-MIX). Both IL-3 and GM-CSF also induced proliferation of CD34+ in liquid cultures. Proliferative responses to IL-3 were found to be more rapid and stronger than to GM-CSF, although the number of initial responsive cells as judged by autoradiography were comparable. Enhanced proliferation of CD34+ cells both in semi-solid and liquid cultures was obtained in the presence of combinations of IL-3 and GM-CSF. The responses observed were less than additive, with the exception of the development of eosinophil colonies and clusters, where IL-3 and GM-CSF were found to act synergistically. In secondary cultures, proliferative responses to GM-CSF were strongly enhanced by preculture of CD34+ cells in IL-3 for four to 11 days, and to a lesser extent by preculture in GM-CSF. Finally, responses to IL-3 were not affected by preculture of CD34+ cells in the presence of GM-CSF. Our results indicate that there is a wide overlap of cells capable of proliferating either in response to IL-3 or to GM-CSF within the cord blood CD34+ compartment. However, differences in primary proliferation kinetics and increased responsiveness to GM-CSF following preculture suggest the importance of a sequential action of IL-3 and GM-CSF in the expansion of CD34+ cells.

Antigens, CD34↗
PubMed1989

Sequential loss of CD34 and class II MHC antigens on purified cord blood hematopoietic progenitors cultured with IL-3: characterization of CD34-, HLA-DR+ cells.

The expression of class II MHC and CD34 antigens on human cord blood hematopoietic progenitor cells (HPC) was investigated upon culturing in the presence of interleukin-3 (IL-3). HPC isolated by "panning" according to their expression of CD34 coexpressed HLA-DR and HLA-DP, and the majority of the CD34+ HPC also expressed HLA-DQ. In the presence of IL-3, the expression of CD34 and class II MHC antigens was found to be gradually lost in culture. Loss of CD34 expression preceded loss of HLA-DR expression. After eight days of culture, CD34-, HLA-DR+ blast cells were obtained that strongly proliferated in response to IL-3, GM-CSF, G-CSF, and M-CSF, and that had the capacity to generate macrophage and granulocyte colonies. After ten days of culture in IL-3, a population of CD34- cells that expressed low levels of HLA-DR (HLA-DRlo) was obtained by FACS-sorting. These CD34-, HLA-DRlo cells lacked colony-forming activity while the population expressing high levels of HLA-DR (HLA-DRhi) contained great numbers of colony-forming cells, and proliferated stronger in response to CSFs than the HLA-DRlo fraction. Finally CD34-, HLA-DR- cells that appeared later in the cultures (14 to 16 days) represented more differentiated cells with only marginal proliferative and no clonogenic capacity. These data indicate that whereas CD34 expression is associated with the multilineage potential of the HPC, HLA-DR expression correlates with overall proliferative capacity of hematopoietic cells during culture in IL-3.

Antigens, CD34↗
PubMed1988

Effects of recombinant human interleukin-3 on CD34-enriched normal hematopoietic progenitors and on myeloblastic leukemia cells.

Induction of proliferation and differentiation in response to recombinant human interleukin-3 (hIL-3) was studied in liquid and semisolid cultures of umbilical cord blood and bone marrow cells that were fractionated by "panning" with anti-My10 antibody according to expression of CD34 antigen. Cells from enriched fractions (70% to 90% CD34+) were found to proliferate strongly in response to hIL-3. Phenotypic analysis and morphologic characterization of the proliferating cells demonstrated a rapid decrease in CD34+ cells and an exponential increase in the number of cells belonging to the neutrophilic, eosinophilic, monocyte/macrophage, and thrombocytic lineages. When combined with recombinant human erythropoietin, burst colonies and cells expressing glycophorin-A were detected, thereby demonstrating the effects of hIL-3 on erythroid progenitors. Further, the development of mixed-erythroid colonies indicated that multipotential cells within CD34-enriched fractions responded to hIL-3. In addition, we examined the effect of hIL-3 on the proliferation of primary acute myeloblastic leukemia cells in liquid culture. We found that hIL-3 was able to induce cell proliferation in a proportion of the cases tested. Heterogeneity of the responses to hIL-3 was in part related to French-American-British classification but could not be correlated with CD34 antigen expression by the leukemic cells. These results indicate that, although the effects of hIL-3 on proliferation and differentiation of cells obtained from normal hematopoietic specimens were primarily borne by CD34+ cells, expression of the CD34 molecule per se is an insufficient condition to determine a growth response to this lymphokine.

Antigens, CD34↗
PubMed1985

Immunochemical mapping of alpha-2 interferon.

A panel of five monoclonal antibodies, designated U1-U5, produced by murine hybridoma clones has been raised to recombinant interferon (IFN) alpha-2, and one monoclonal antibody, designated U6, has been raised to a mixture of cyanogen bromide fragments of IFN alpha-2. These antibodies have been characterized with respect to (1) neutralization of IFN antiviral and antiproliferative activities, (2) binding to four cloned IFN alpha subtypes (alpha-1, alpha-2, alpha-4, and alpha-7) that are naturally occurring and to two novel products of recombinant DNA technology (delta-4 alpha-1 and delta-4 alpha-2/alpha-1 hybrid), and (3) binding to three cyanogen bromide fragments of IFN alpha-2. Four of the six monoclonal antibodies inhibited IFN antiviral activity. In conjunction with the previously reported monoclonal antibodies III/21 [Arnheiter, H., Thomas, R. M., Leist, T., Fountoulakis, M., & Gutte, B. (1981) Nature (London) 294, 278-280] and NK-2 [Secher, D. S., & Burke, D. C. (1980) Nature (London) 285, 446-450], eight unique epitopes have been described. Analysis of cross-reactivity patterns with IFN alpha fragments and subtypes indicated that monoclonal antibodies U1 and NK-2, which neutralized both antiviral and antiproliferative activities, and U2, which was nonneutralizing in these assays, were directed to distinct epitopes located in a polypeptide consisting of the amino-terminal 15 amino acid residues linked to residues 60-110 by a disulfide bond. The epitope recognized by U1 was determined to reside, at least in part, between residues 5 and 15. Competitive binding studies indicated that neutralizing monoclonal antibody U3, which did not bind to any of the cyanogen bromide fragments, was directed to an epitope partially overlapping that of NK-2. Epitopes to which neutralizing monoclonal antibodies U3, U4, and U5 and nonneutralizing antibody U6 were directed were readily distinguished by cross-reactivity with IFN alpha subtypes. The nonneutralizing monoclonal antibody U6 was determined to be directed to an epitope between residues 22 and 58. The fact that delta-4 alpha-1 and the delta-4 alpha-2/alpha-1 hybrid were active in an antiviral assay indicated a lack of direct functional significance for the first four amino-terminal amino acid residues and the Cys1-Cys98 disulfide bond. However, reduction with 2-mercaptoethanol of IFN alpha-2 altered the integrity of four of the eight epitopes. These data support a critical role for disulfide linkages in maintaining the native conformation of IFN alpha-2 and provide a potential basis for predicting the location of functionally important domains.

Amino Acids↗
PubMed1985

[Degenerative aphasia].

A woman had difficulties in word finding since age 59, this became a Broca's aphasia then a global aphasia. The only possible expression was written and agrammatic with many semantic errors. Calculation was preserved as well as constructional praxis. Ideomotor praxis was slightly impaired. Visual recognition and somatagnosia were normal. Neurological examination showed neither motor nor sensitive impairment. Visual fields were normal. CT scan at onset was normal. Later a slight cortical atrophy appeared predominating on the sylvian fissures, slightly more severe on the left side. Reviewing the literature the authors draw attention on the possible occurrence of an evolutive aphasia being the first evidence of a dementia. The impairment of the other cognitive functions would only appear after several years.

Aphasia↗