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Biomedical subjects

P Lefebvre

Publications and source records attributed to P Lefebvre.

At least 109 records · Page 6Linked to original sources
PubMed1995

[Pulmonary embolism and pregnancy: report of a case; review of the literature].

Pulmonary embolism occurring during pregnancy is a rare accident but that still brings about a high mother mortality; it seems to be five to six times more frequent during the pregnancy and the post-partum than for non-parturient women who don't take any estro-progestogens, pulmonary embolism would involve complications for 0.5/1000 pregnancies before delivery. As it presents a lot of diagnostic problems, it is under-estimated. The vascular radiological examinations expose the foetus or embryo to considerable radiation and to a risk of foetal hypothyroidism leading to backwardness. The lung perfusion scanning has the advantage of not injecting iodine but is not specific. Fortunately, some medical examinations such as plethysmography or Doppler echography are safe and can also guide the clinician. As far as therapy is concerned, intravenous heparin is the first intention treatment, it can be replaced subsequently by subcutaneous heparin (low molecular weight heparin). In case of heavy pulmonary embolism endangering the vital prognosis of the patient, in case of clinical or biological resistance to the medical treatment, it could be necessary to perform a pulmonary embolectomy with, if necessary, vena cava interruption with insertion of a mechanical filter.

Adult↗
PubMed1994

Cultured myofibroblasts display a specific phenotype that differentiates them from fibroblasts and smooth muscle cells.

BACKGROUND: Myofibroblasts (MF) from human granulation tissue derive from perilesional cells and display similarities with fibroblasts (DF) and smooth muscle cells (SMC). OBJECTIVE: Determine additional markers to assess the phenotype of MF. METHODS: MF, DF and SMC derived from human tissues were amplified in culture. Their phenotype and response to various regulatory processes were compared in vitro. RESULTS: MF resemble SMC by their mechanical properties and cytoskeletal proteins. They resemble DF by their biosynthetic phenotype and their response to the regulation operated by the extracellular matrix and mechanical forces. CONCLUSION: In vitro MF display a phenotype that differentiates them from DF and SMC.

Cells, Cultured↗
PubMed1994

[Economic welfare of Canadian children: changes and implications for social policy].

"This study recommends courses of action within the scope of social policy revision in Canada, aiming to increase funding for children. These recommendations stem from a critical review of guaranteed income programmes and an analysis of the actual economic welfare of children. The authors describe the evolution of the nature of the family in Canada over the past twenty years and of the economic status of children. Their assessments are based on an analysis of cross-sectional micro-level data on income and socio-economic characteristics drawn from a very large sample of Canadian families." (SUMMARY IN ENG AND SPA)

Adolescent↗
PubMed1994

[Fertility behavior in Quebec, family allowances, and taxes: results and simulations with a discrete choice model for the years 1975-1987].

"We suppose that women (couples), who are less than 40 years old, are faced with three types of sequential decisions: the fertility decision, the decision relative to the number of children to have and the decision concerning labour force participation.... We use a nested polychotomous discrete choice model to estimate the responsiveness of the behaviour of 'married' women in Quebec to variations in the expected flow of revenue resulting from changes in the parameters of the personal income tax and in the level of public monetary transfers conditional on the number of children. The model is estimated with micro-data from 9 repeated cross-sections for the years 1975 to 1987 with a full information maximum likelihood method.... This empirical setting is used to simulate the effects of changes made to the fiscal and transfer policies in favor of families with dependent children on fertility, [women's] labor force participation and the importance of spending costs for the two levels of government." (SUMMARY IN ENG)

Aid to Families with Dependent Children↗
PubMed1994

In vitro all-trans retinoic acid (ATRA) sensitivity and cellular retinoic acid binding protein (CRABP) levels in relapse leukemic cells after remission induction by ATRA in acute promyelocytic leukemia.

The current treatment of acute promyelocytic leukemia (APL, also called AML3 subtype) is focused on differentiating agents such as the vitamin A derivative all-trans retinoic acid (ATRA). This agent is a novel and very promising therapy for this disease characterized cytogenetically by a translocation t(15;17)(q21;q22) involving the alpha retinoic acid receptor on chromosome 17 and the PML gene on chromosome 15. Clinical trials have demonstrated that ATRA followed by or combined with conventional chemotherapy may be more beneficial than chemotherapy for inducing complete remission. Unfortunately, ATRA as a single agent, does not appear able to maintain patients in remission (median 5 months), and when relapse occurs resistance to a second induction of ATRA therapy is observed in almost all cases. Recently our laboratory investigated whether specific features of the AML3 cells at relapse could explain the in vivo resistance observed. We have demonstrated that AML3 patients' cells (from four patients) at relapse show high levels of CRABP, a cytosolic retinoic acid binding protein and this protein was not detected prior to ATRA therapy. Relapse-AML3 cells (n = 12) showed reduced differentiation induction when compared with 'virgin'-AML3 cells. Results from this study suggest that CRABP could modulate ATRA cellular concentrations reaching the nucleus. This induced ATRA hypercatabolytic state should be monitored during consolidation therapy and at relapse by evaluating CRABP and RA metabolite levels, in order to detect ATRA resistance in patients with AML3.

Clinical Trials as Topic↗
PubMed1994

Retinoic acid receptors: involvement in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL), is a homogeneous subgroup of acute myelogenous leukemias characterized by phenotypic and genetic markers. APL is associated with a reciprocal chromosomal translocation t(15,17) which has been shown to disrupt the retinoic acid receptor alpha (RAR alpha) gene. As a result, a portion of the RAR alpha gene becomes fused with a chromosome 15 locus termed PML (promyelocytic myeloid leukemia) from which chimeric PML/RAR alpha fusion mRNAs are expressed. The presence of these fusion transcripts in APL patients strongly support the hypothesis that both the t(15;17), and thus PML/RAR alpha, play a crucial role in the leukemogenesis of this disease. APL cells are specifically responsive to all-trans retinoic acid (ATRA) and this characteristic has allowed the first differentiation therapy with retinoic acid. However, failure or partial responses are observed and, though this has most frequently been reported in patients at second or third relapse. The molecular basis of the absence of ATRA response in these patients has not been determined.

Cell Differentiation↗
PubMed1994

In vitro all-trans retinoic acid (ATRA) sensitivity and cellular retinoic acid binding protein (CRABP) levels in relapse leukemic cells after remission induction by ATRA in acute promyelocytic leukemia.

The current treatment of acute promyelocytic leukemia (APL, also called AML3 subtype) is focused on differentiating agents such as the vitamin A derivative all-trans retinoic acid (ATRA). This agent is a novel and very promising therapy for this disease characterized cytogenetically by a translocation t(15;17)(q21;q22) involving the alpha retinoic acid receptor on chromosome 17 and the PML gene on chromosome 15. Clinical trials have demonstrated that ATRA followed by or combined with conventional chemotherapy may be more beneficial than chemotherapy for inducing complete remission. Unfortunately, ATRA as a single agent, does not appear able to maintain patients in remission (median 5 months), and when relapse occurs resistance to a second induction of ATRA therapy is observed in almost all cases. Recently our laboratory investigated whether specific features of the AML3 cells at relapse could explain the in vivo resistance observed. We have demonstrated that AML3 patients' cells (from four patients) at relapse show high levels of CRABP, a cytosolic retinoic acid binding protein and this protein was not detected prior to ATRA therapy. Relapse-AML3 cells (n = 12) showed reduced differentiation induction when compared with 'virgin'-AML3 cells. Results from this study suggest that CRABP could modulate ATRA cellular concentrations reaching the nucleus. This induced ATRA hypercatabolytic state should be monitored during consolidation therapy and at relapse by evaluating CRABP and RA metabolite levels, in order to detect ATRA resistance in patients with AML3.

Drug Screening Assays, Antitumor↗
PubMed1993

Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia.

It has been shown that all-trans retinoic acid (ATRA) at doses of 45 to 100 mg/m2/d induces complete remission (CR) of acute promyelocytic leukemia (APL) by a differentiation process. To date, ATRA dose-ranging studies have not yet been evaluated. Thus, we initiated in May 1990 a multicenter study with ATRA at a lower dose of 25 mg/m2/d until CR. Thirty patients with APL were treated with ATRA, of whom 12 were previously untreated, 14 were in first relapse, and 4 had failed after conventional first induction chemotherapy. Twenty-four of 30 achieved CR, 3 failed, and 3 died before day 30. Median time to CR was 45 days. Hyperleucocytosis (14 to 43 x 10(9) white blood cells per liter) was observed in 9 patients between days 10 and 23. Clinical complications that may have been related to the retinoic acid syndrome were observed in 8 patients, of whom 3 died. Pharmacokinetics studies were performed in 5 patients. Peak plasma concentrations and mean area under the concentration-time curve were not lower than previous levels obtained under the 45 mg/m2 dose. Overall, our study shows that there is no difference in terms of therapeutic efficacy, triggering of hyperleukocytosis, or retinoic acid syndrome and pharmacokinetic results with ATRA at 25 or 45 mg/m2/d.

Administration, Oral↗
PubMed1993

[Case report of an adrenal hemorrhagic pseudocyst. Literature review].

Cysts and pseudocysts of the adrenal gland are usually discovered fortuitously, either on clinical examination or on the occasion of a radiological check-up for a non specific symptomatology. Their diagnosis rests on several examinations such as intravenous pyelography, ultrasounds, computerized tomography or arteriography. The final diagnosis relies on the histological examination of removed material. Surgery is systematically advocated as the actual nature of the tumor cannot be established preoperatively.

Adrenal Gland Diseases↗
PubMed1993

Induction of O6-methylguanine-DNA-methyltransferase and N3-methyladenine-DNA-glycosylase in human cells exposed to DNA-damaging agents.

The inducibility of two DNA repair proteins, the O6-methylguanine-DNA-methyltransferase (MGMT) and the N3-methyladenine-DNA-glycosylase (ANPG), was studied by measuring the protein activities and the transcription of the MGMT and ANPG genes in a human hepatoma cell line (LICH cells). The two protein activities are enhanced after treatment with a variety of DNA-damaging agents. They are maximum 72 hr after the inducing treatments and remain elevated for about 120 hr. This induction is abolished when the cells are grown in the presence of protein or RNA synthesis inhibitors. Northern blot analysis shows that the DNA-damaging agents increase to different extents the transcription of the MGMT or ANPG genes. The transferase activity is also increased by DNA damage in a human glioblastoma cell line (T98G cells), but is not significantly modified in human normal fibroblasts, suggesting that this repair activity enhancement might occur preferentially in transformed cells, as we have previously shown for cells of rat origin. Therefore, these increased repair activities may play an important role in removing the lethal N3-methyladenine residues, the promutagenic O6-methylguanine lesions, and the potentially lethal chloroethyl adducts formed by the nitrosoureas used in cancer chemotherapy more efficiently from the cellular DNA.

Animals↗
PubMed1993

A human cell line proficient in O6-methylguanine-DNA-methyltransferase and hypersensitive to alkylating agents.

The involvement of O6-methylguanine (O6-meGua) in mutagenesis is well established, while the toxic effect of these residues is still controversial. In this study, we compare the cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU) on three cell lines of different origin, which have different abilities to repair O6-meGua residues (Mer phenotype): a human hepatoma cell line (LICH cells, Mer+), a rat hepatoma cell line (H4 cells, Mer+) and a Chinese hamster cell line (CHO cells, Mer- phenotype). LICH and CHO cells show the same sensitivity to the killing effect of MNNG and MNU and are approximately 5-fold more sensitive than H4 cells. However, LICH and H4 cells share similar sensitivities to the toxic effect of 1,3-bis(2-chloroethyl)-1-nitrosourea. O6-meGua residues are removed at the same rate from the DNA of [3H]MNU-treated LICH and H4 cells, which also do not differ in the rate of removal of N3-methyladenine residues nor in overall DNA repair synthesis. The results suggest that MNNG and MNU produce a lethal lesion that is repaired by a process that does not involve the alkyltransferase.

Alkylating Agents↗
PubMed1993

A protein kinase C-dependent activity modulates retinoic acid-induced transcription.

The retinoic acid receptors (RARs) and retinoid X receptors, which are members of the nuclear receptor family, mediate the effects of vitamin A derivatives on cellular growth and differentiation. The protein kinase C isozyme family also controls these processes in response to extracellular stimuli. We have investigated the relationship between these two signal transducing pathways using gene transfer techniques. We show that selective inhibition of protein kinase C (PKC) and its depletion by prolonged treatment with 12-O-tetradecanoylphorbol-13-acetate lead to the loss of ligand-dependent transcription of an RA-inducible promoter. The effect of the depletion in cellular PKC could be counteracted by overexpression of PKC alpha and is directly correlated to the loss of the DNA-binding activity of complexes containing the human RAR alpha (hRAR alpha). Indirect immunofluorescence studies demonstrated an altered subcellular localization of hRAR alpha. However, direct in vitro phosphorylation of hRAR alpha by PKC diminished its ability to form heterodimeric or homodimeric complexes on a retinoic acid response element, suggesting that the DNA-binding capacity of hRAR alpha in intact cells is indirectly controlled by a PKC-dependent mechanism. Thus our observations establish a functional link between the PKC and retinoid pathways, which are generally considered to have antagonistic activities on differentiation processes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗