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C Favre

Publications and source records attributed to C Favre.

At least 19 recordsLinked to original sources
PubMed1996

Clinical and experimental pharmacokinetic interaction between 6-mercaptopurine and methotrexate.

Clinical and experimental pharmacokinetic interaction between 6-mercaptopurine (6-MP) and methotrexate (MTX) was investigated in patients as well as in rats and in HL-60 human leukemic cells. Ten children affected by acute lymphoblastic leukemia (ALL) in remission received daily doses of 6-MP given at 25 mg/m2 and i.v. infusion of high-dose MTX at 2 or 5 g/m2 once every other week. When 6-MP was given alone, the mean peak plasma concentration (Cmax) and area under the curve (AUC) of 6-MP were 72.5 ng/ml and 225.3 h ng ml(-1). Concurrent treatment with MTX at 2 or 5 g/m2 resulted in a mean increase of 108% and 121% in the Cmax and of 69% and 93% in the AUC, respectively. In rats treated with an oral dose of 6-MP at 75 mg/m2, MTX given i.p. at 5 g/m2 produced mean increases of 110% and 230% in the Cmax and AUC of 6-MP, respectively. In HL-60 human leukemic cells incubated with 6-MP at 250 ng/ml, the cumulative intracellular concentration of 6-thioguanine and 6-MP nucleotides was not significantly modified by treatment with 20 micrograms/ml of MTX. The present findings indicate that high-dose MTX enhances the bioavailability of 6-MP as evidenced by the observed increases in the plasma Cmax and AUC of 6-MP in humans and animals.

Adolescent↗
PubMed1995

Is intestinal cytosolic glutathione S-transferase an alternative detoxification pathway in two-thirds hepatectomized rats?

The present study was designed to investigate the effect of partial (two-thirds) hepatectomy (PH) on hepatic and intestinal glutathione S-transferases (GSTs) activities. A significant decrease of cytosolic hepatic GSTs activity was observed after the PH. The lowest value of hepatic GSTs was obtained 48 h after the surgery. On the other hand, intestinal GSTs activities increased after PH, reaching the highest values 48 h after the hepatic lobes resection. The hepatic GSTs activities diminution was attributed, in part, to the high accumulation of bile acids in the liver tissue of hepatectomized rats, also demonstrated by a higher retention of [14C] taurocholate. The kinetic analysis performed with 1-chloro-2,4-dinitrobenzene (CDNB) as substrate showed two sets of parameters, indicating the presence of isozymes of high and low affinities. Vmax1 and Vmax2 were lower in PH rats suggesting a non competitive inhibition mechanism. The inhibitory effect of bile acids decreased during liver regeneration process of hepatectomized rats disappearing at 7 days after PH. Conversely, in non regenerating rats (GABA treated) the inhibitory mechanism was still observed at 7 days after the surgery. The increase of intestinal GSTs activities (isozymes of high and low affinities) was attributed to the presence of polyamines, mainly putrescine, produced during the hepatic regeneration process. In this regard, it was showed that GABA treatment, which inhibits polyamine synthesis, completely abolished the increase on intestinal GSTs activities. Finally, the treatment with exogenous putrescine showed that in hepatectomized and sham-operated rats, the polyamine induced GSTs activities in both tissues. In PH rats, the putrescine dependent increase of hepatic GSTs was masked by the inhibitory effect of bile acids. In addition, a summation effect of endogenous and exogenous putrescine was probably the reason of the induction of intestinal GSTs after PH. The GSH/GSSG ratio did not change during the treatments, as well as the microsomal GST activity of both tissues. The work points out the hypothetical detoxification power of the intestine during the hepatocellular insufficiency which follows a two-thirds hepatectomy.

Animals↗
PubMed1995

Acute regulation of hepatic glutathione S-transferase by insulin and glucagon.

The intravenous administration of insulin plus glucose in anesthetized rats caused, within 30 min, an increase of about 56% in hepatic cytosolic glutathione S-transferase (GST) activity, but it did not affect the microsomal enzyme. The injection of glucagon resulted, at the same time, in a 43% drop in the hepatic cytosolic GST, without affecting the microsomal GST. The insulin-dependent increase in cytosolic GST activity was abolished by the pretreatment of the animals with an inhibitor of protein synthesis (cycloheximide). A kinetic analysis revealed a non-competitive inhibition caused by glucagon upon the cytosolic enzyme. In addition, the presence of insulin did not interfere with the effectiveness of glucagon, and vice versa. We propose that: (1) the effect of insulin on hepatic cytosolic GST activity requires protein synthesis; (2) glucagon produces an inhibition of hepatic cytosolic GST, which could be mediated by cytosolic effectors such as adenosine 3'-5'-cyclic monophosphate (cAMP); (3) the effects of glucagon and insulin were not mutually exclusive; (4) hepatic microsomal GST is regulated by different mechanism(s).

Animals↗
PubMed1994

[Uveitis in the elderly].

BACKGROUND: There is only scarce information available in the literature on uveitis of older patients. The aim of this study was to study this age group in greater detail. PATIENTS AND METHODS: 435 patients were seen in the uveitis clinic of the University Eye Hospital Jules Gonin from January 1990 to March 1993. We analysed here the 94 (21.8%) patients that presented a first episode of uveitis after the age of sixty. RESULTS: This collective was characterised by an increased frequency of the anatomic diagnosis of panuveitis (p < 0.0001), and of the specific diagnosis of zoster uveitis (p < 0.0001), sarcoidosis (p < 0.0001), uveitis associated with scleritis (p < 0.05) and granulomatous anterior uveitis (p < 0.01). The frequency of diagnosis of intermediate uveitis was significantly reduced (p < 0.034) as were the specific diagnosis of HLA-B27 positive acute anterior uveitis (p < 0.001), pars planitis (p < 0.08) and non granulomatous anterior uveitis (p < 0.01). Reiter's uveitis, Possner-Schlossmann Syndrome, Behçet's uveitis, Vogt-Koyanagi-Harada disease and Toxoplasmosis retinochoroiditis were never diagnosed in this group of elderly patients. The proportion of defined specific diagnosis (75.5%) was comparable to the group of patients of less than 60 years old. CONCLUSION: As can be seen from our data, epidemiological characteristics of old age uveitis differ markedly from younger patients which should influence the diagnostic approach in these patients.

Aged↗
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↗
PubMed1993

[Continuity and discontinuity of psychopathology: a study of patients examined as children and as adults. II. Childhood antecedents of drug dependent adults].

The demographic stability of the Swiss Canton of Geneva provided us with the necessary conditions for a follow-up study of the entire childhood population who, having consulted the Child Psychiatry Services between 1963 and 1967, later consulted the adult public psychiatric services (720 cases). We looked for specific clusters of clinical signs which would enable us to differentiate, statistically speaking, the groups of children according to their adult diagnosis. We present here the results for the group of children who were diagnosed at adulthood as drug addicts (DSM III R). We found a specific cluster significantly differentiating these children from the other populations. It includes: a personality disorder (undifferentiated behaviour, and solitary and aggressive behaviour), environmental factors (monoparental, rejecting family) and a lack of mental deficiency.

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↗