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Biomedical subjects

J Fournier

Publications and source records attributed to J Fournier.

At least 37 records · Page 2Linked to original sources
PubMed1998

Prognostic value of p53 and urokinase-type plasminogen activator in node-negative human breast cancers.

We measured the levels of p53 and urokinase-type plasminogen activator (uPA) in 634 tumor tissues from 634 different node-negative primary breast cancer patients who underwent locoregional surgery in the Center Oscar Lambret between July 1989 and September 1994. p53 and uPA were assayed using commercially available kits in cytosols prepared for estradiol receptor (ER) and progesterone receptor (PgR) assays. The optimum clinical thresholds were chosen for prognostic studies: 4 ng/ml for p53 and 0.5 ng/ml for uPA. p53 was elevated in 13.7% of the tumors, and uPA was elevated in 27.5% of the tumors; they were negatively related (chi 2 test) to ER and PgR and positively related to histoprognostic grading (HPG) and tumor diameter. uPA was negatively correlated to ER and PgR, and p53 and uPA were positively correlated to each other (P = 0.0001; Spearman test). In the prognostic studies, the 316 patients who did not receive adjuvant chemotherapy were included to avoid treatment interference; this number corresponds to all of the patients operated on between 1989 and 1992. The mean duration of follow-up of living patients was 4 years. In overall survival studies, Cox univariate analyses demonstrated a prognostic value of p53 (P = 0.011; risk ratio, 1.59), uPA (P = 0.038; risk ratio, 2.32), PgR, HPG, and tumor diameter. In Cox multivariate analyses, only HPG had a statistically significant prognostic value. In relapse-free survival studies, univariate analyses demonstrated prognostic values of uPA (P = 0.0011) and of age, and both parameters retained their prognostic value in multivariate analyses (uPA: P = 0.0004). This study demonstrates not only that p53 and uPA have prognostic value but also that these two parameters are linked to other classical clinical, histological, or biological prognostic parameters, as well as to each other. Moreover, because uPA is of prognostic value in multivariate relapse-free survival studies, uPA is an important prognostic factor in node-negative breast cancer patients.

Adult↗
PubMed1997

A comparison of conventional microscopy, immunofluorescence microscopy and flow cytometry in the detection of Giardia lamblia cysts in beaver fecal samples.

A variety of domestic and wild animals are considered to be potential sources of giardiasis in humans. As a result, numerous studies have been reported on the prevalence of Giardia lamblia infection in animals. The majority of these surveys have involved various floatation techniques followed by conventional microscopy in order to detect cysts in fecal samples. Immunofluorescence microscopy has become popular in recent years for the detection of G. lamblia cysts in both clinical and environmental samples. This technique can be automated by combining it with flow cytometry. The present study represents a direct comparison of conventional microscopy, immunofluorescence microscopy, and flow cytometry in terms of their relative efficiency in the detection of G. lamblia cysts in beaver fecal samples. As a result of viewer fatigue, or low cyst concentrations, false negatives were common with conventional microscopy, leading to low prevalence estimates. By specifically targeting the cysts, immunofluorescence microscopy provided more reliable results in a shorter time than conventional methods. When flow cytometry was used in combination with immunofluorescence, a larger number of samples could be examined in a relatively short period of time. The results obtained indicated that this technique allowed for more consistent recognition than either conventional or immunofluorescence microscopy of positive samples containing smaller numbers of cysts.

Animals↗
PubMed1997

Determination of intervillous flow in early pregnancy.

The process of placentation in the macaque has been extensively studied and found to resemble closely that observed in the human. In this model, histopathologically, intervillous flow is anticipated from week 3 post-conception. We set out to document the nature and onset of intervillous flow in the macaque in vivo using colour Doppler imaging (CDI), colour Doppler energy (CDE) and pulsed-wave Doppler (PWD). Pregnant females were assessed between 15-50 days gestation (term = 165 days) with an Acuson 128/XP10 high-resolution ultrasound scanner, using a 7-MHz linear array probe. The placenta, subjacent decidua and myometrium were assessed using CDI and CDE. Specific regions of flow were interrogated using PWD; the resulting flow velocity waveforms were stored and quantified using conventional Doppler indices. B-mode sonography was able to demonstrate the well-defined placental-decidual interface observed in this species; CDI and CDE clearly visualized the uteroplacental vasculature. Spiral arteries were followed to their point of discharge into the intervillous space, and PWD at these sites obtained a characteristic flow velocity waveform. The indices obtained confirmed a flow of low resistance and pulsatility throughout the gestation studied. Flow within the intervillous space was noted from day 20 of gestation.

Animals↗
PubMed1996

Isolation and sequence analysis of Clpg1, a gene coding for an endopolygalacturonase of the phytopathogenic fungus Colletotrichum lindemuthianum.

Oligodeoxyribonucleotide primers designed from the N-terminal amino acid (aa) sequence of the endopolygalacturonase (EndoPG) of Colletotrichum lindemuthianum (Cl) race beta and from an internal sequence conserved among different fungal EndoPG were used in a polymerase chain reaction (PCR) to amplify genomic related sequences of the fungus. A 542-bp fragment, designated pgA, was obtained and used as a probe to screen a partial genomic library of Cl. Among the positive clones, one was further analyzed. Nucleotide sequencing of this clone revealed on ORF encoding a 363-amino-acid (aa) polypeptide beginning with a signal peptide of 26 aa interrupted by an intron of 70 bp, and showing a high degree of homology to ten fungal EndoPG sequences. Consensus sequences were identified in the 5' non-coding region. This genomic clone was thereafter designated Clpg1. Southern analysis, performed with a Clpg1-specific probe, showed that this gene is present as a single copy in the Cl genome.

Base Sequence↗
PubMed1996

Effect of serotonin on cytokine mRNA expression in rat hippocampal astrocytes.

Serotonin is a widely distributed neurotransmitter which elicits a range of central activities. We examined the effect of serotonin on cytokine mRNA expression by rat hippocampal astrocytes in primary cultures. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis shows that interleukin-6 (IL6) mRNA is expressed after 10(-12) M serotonin stimulation whereas transforming growth factor-beta (TGF beta) and tumor necrosis factor (TNF alpha) are induced by 10(-10) M serotonin. These inductions appeared after 1 h stimulation for IL6 and TNF alpha, whereas that of TGF beta appeared after 4 h. The present results provide the first evidence that serotonin can influence astrocyte cytokine production, and thus this neurotransmitter may be considered a potential neuroimmunomodulator.

Animals↗
PubMed1996

Lipoxygenase gene expression in the tobacco-Phytophthora parasitica nicotianae interaction.

A recently isolated cDNA clone of tobacco (Nicotiana tabacum L.) lipoxygenase (LOX) was used to study LOX gene expression in tobacco cell-suspension cultures and intact plants in response to infection with Phytophthora parasitica nicotianae (Ppn). Southern blot analysis of tobacco DNA indicated that only a small number of LOX genes hybridize to this probe. These genes were not constitutively expressed to a detectable level in control cells and healthy plants. In contrast, a rapid and transient accumulation of transcripts occurred in cells and plants after treatment with elicitor and inoculation with zoospores of Ppn, respectively. In cell cultures LOX gene expression could also be induced by linolenic acid, a LOX substrate, and by methyl jasmonate, one of the products derived from the action of LOX on linolenic acid. In the infection assays, LOX gene expression and enzyme activity were observed earlier when the plants carried a resistance gene against the race of Ppn used for inoculation. The differential expression of LOX during the race-cultivar-specific interaction between tobacco and Ppn, as well as its regulation by elicitors and jasmonate, suggest a role of LOX in plant resistance and establishment of the defense status against this pathogen.

Cells, Cultured↗
PubMed1996

Cell surface marker evaluation of infant Macaca monkey leukocytes in peripheral whole blood using simultaneous dual-color immunophenotypic analysis.

Cross-reactivity between several commercially available mouse antihuman monoclonal antibodies (mAbs), conjugated to phycoerythrin (PE) and fluorescein isothiocyanate (FITC) fluorochromes, and peripheral blood leukocyte surface antigens, has been established in infant cynomolgus (Macaca fascicularis) monkeys using whole blood lysis, and two-color, PE and FITC flow cytometric analysis. With the exception of the CD8 marker, the bivariate dot-plot patterns for all other markers were similar in infant monkeys and in humans. For the CD8 marker, however, a CD8+CD2- population of cells was observed in the majority of monkeys tested (10 out of 12). The number of CD8+CD2- cells was higher (13%) in infant monkeys compared to the 3% reported for adult human blood. The mean percentage and absolute numbers for the cell surface markers identified with the human mAbs CD2 (FITC, Ortho, Paritan, NJ), CD4 (PE, B-D, Mountain View, CA), and CD8 (PE, B-D) when these were combined with a series of PE- or FITC-labelled human mAbs were similar across all combinations tested. Statistically significant differences were observed between male and female monkeys for the mean percentage levels of CD4 (females > males) and for the CD4/CD8 ratio (females > males). Such gender differences need to be taken into consideration when infant cynomolgus monkeys are used as models for chemical-induced immunotoxicity studies. Measurement of the interleukin-2 (IL-2) and transferrin proved to be useful in monitoring in vitro cellular activation in infant cynomolgus and possibly in rhesus (M. mulatta) monkeys.

Adult↗
PubMed1995

[Surveillance and rehabilitation of cancers of upper respiratory and digestive tracts].

Follow-up of head and neck cancers after treatment is usually done by specialists every 2 to 3 month during an indeterminate period. The aim of this follow up is to detect a recurrence or a complication due to the treatment. Xerostomia, endolaryngeal and cutaneous modifications are the most frequent sequelae of irradiation. Major surgery of the larynx require a speech rehabilitation which gives correct results in 70% of the cases. Professional rehabilitation is possible for few patients: only 50% of the patients who had jobs before treatment were able to go back to work. The return to work was more often seen among civil servants, and workers than among craftsmen. Laryngectomised people resume their work less often than other head and neck cancer patients. There is no problem with social rehabilitation.

Disability Evaluation↗
PubMed1995

Prognostic significance of circulating P53 antibodies in patients undergoing surgery for locoregional breast cancer.

P53 mutations can lead to the production of P53 antibodies in serum of cancer patients. Here we studied the prognostic value of P53 antibodies in 353 primary breast cancer patients. P53 antibodies were detected in 42 cases (12%) and were negatively related to oestradiol and progesterone receptors. The median duration of follow-up for live patients was 5.3 years. In actuarial analyses, overall survival was worse in patients with P53 antibody (p < 0.0005); in Cox's multivariate analysis, P53 antibody was an independent prognostic variable. Thus plasma assay of P53 antibody would be useful to select rapidly and easily a population of patients with poor prognosis.

Adenocarcinoma↗
PubMed1995

Analysis of p16 gene deletion and point mutation in breast carcinoma.

We looked for p16 gene deletion by Southern analysis and p16 gene point mutation by single-stranded conformation polymorphism (SSCP) analysis and direct sequencing of DNA from fresh tumour samples of 35 and 33 breast carcinomas respectively. No homozygous p16 gene deletion was found in any case. A missense point mutation of the p16 gene was found in only one patient. This point mutation was absent from the patient's lymphocytes, ruling out a polymorphism or a germline mutation. These findings suggest that p16 gene alterations are rarely observed in breast carcinoma.

Base Sequence↗
PubMed1995

Cytotoxic and transforming effects of some iron-containing minerals in Syrian hamster embryo cells.

Four physicochemically characterized iron-containing minerals, one fibrous (a nemalite [brucite]) and three nonfibrous (a biotite [phyllosilicate], a magnetite (Fe3O4), and a goethite [FeOOH alpha]), were studied for cytotoxicity and morphological transformation of Syrian hamster embryo (SHE) cells. When colony-forming efficiency was used as a measure of cytotoxicity, it appeared that the nemalite was about 1.7-fold more cytotoxic than the biotite and magnetite. However, if the inhibitory effect on the cell growth was considered the nemalite appeared to be 8-fold more effective. The analysis of the cell cycle kinetics by flow cytometry revealed a time- and dose-dependent delay in the progression of cells through the cell cycle, with the accumulation of cells in S and G2-M phases, more particularly in the cultures treated with nemalite. While the goethite was neither cytotoxic nor transforming, the other three dusts were, in a dose-dependent manner, efficient in inducing morphological transformation of SHE cells. According to their transforming potency they ranged as follows: nemalite > biotite > magnetite. A 18-fold higher treatment concentration of magnetite than that of nemalite was necessary to induce the same transformation frequency. The iron chelator desferrioxamine abolished the transforming effect of nemalite. The results suggest that (i) the cytotoxicity and the transformation are induced by some divalent iron-containing minerals and that they are two distinct processes; (ii) there is a varying ability among these dusts to induce cell transformation; and (iii) the bioavailability of divalent iron leading to formation of reactive iron-oxygen species could mediate the transforming potency of a mineral. Physicochemical studies correlated to biological effects of many metallic mine dusts are the only approach for understanding their mechanisms of action and their role in occupational pathology.

Aluminum Silicates↗
PubMed1995

[Lipid peroxidation in the presence of inorganic compounds. Relation to oxidative stress mechanisms].

Oxidizing activity study of inorganic compounds is based on a mechanistic approach. This approach implies research of the capacity of these materials, after interaction with molecular oxygen, to generate activated oxygen species (AOS) in aqueous medium. These electrophilic species are able to participate in oxidative stress processes and some AOS differ in their oxidizing power; highly oxidizing species (A*) and entities (P*) less oxidizing than A*. These AOS are capable of initiating linolenic acid peroxidation leading to formation of different degradation products such MDA, monoaldehydes, conjugated dienes and trienes, hydroperoxydes, and ethane. The detection of these products allows to reveal the presence of AOS. Our data show that the global assessment of lipid peroxidation should be established from the whole of formed peroxidation products and not from one type of degradation products.

Asbestos, Serpentine↗
PubMed1994

MDM2 gene amplification in human breast cancer.

The MDM2 gene is a gene whose product binds to p53 and regulates its functions. The amplification of the MDM2 gene has been found in one third of human sarcomas, and a differential expression of MDM2 gene in relation with oestrogen receptor status was recently found in human breast cancer cell lines. We analysed 60 breast cancers for MDM2 gene amplification by Southern blot. This event was observed in 1 case with high levels of oestrogen receptor (ER). Thus, MDM2 gene amplification seems to be a rare event in breast cancer. Further studies are needed to define precisely the relationship between MDM2 amplification and ER status.

Blotting, Southern↗
PubMed1993

Protective effects of SR 57746A in central and peripheral models of neurodegenerative disorders in rodents and primates.

Compounds possessing neurotrophic properties may represent a possible treatment for neurodegenerative disorders such as Alzheimer's disease. SR 57746A, 1-[2-(naphth-2-yl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,5,6- tetrahydropyridine hydrochloride, is a new compound with neurotrophic activity in a number of in vitro preparations. The neurotrophic effects of this compound have been evaluated in vivo using four distinct rat models of neurodegeneration: transient global ischaemia produced by a four-vessel occlusion; septohippocampal lesion produced by injection of vincristine sulphate into the medial septum; sciatic nerve crushing; and acrylamide-induced peripheral neuropathy. Rats were administered vehicle or 2.5-10 mg/kg p.o. SR 57746A, after initiation of the degenerative process, then once daily for 10 days in the first two models, 16 days in the third and 26 days in the fourth model. Median scores for ischaemia-induced neuronal damage were reduced by 30-40% by SR 57746A treatment in hippocampal CA1, CA2, and CA3 regions, and in the dorsal striatum. Twelve days after intraseptal vincristine administration, there was a marked loss of septohippocampal cholinergic neurons, as indicated by reduced choline acetyltransferase activity in both the septum and hippocampus. SR 57746A dose-dependently reversed this reduction in both areas. These results were confirmed by histoenzymological evaluation of hippocampal acetylcholinesterase content. SR 57746A also reversed the loss of hippocampal choline acetyltransferase induced by intraseptal vincristine in marmosets. Behavioral deficits in these models (exploratory behaviour in the former and short-term social memory in the latter) were also significantly reduced by SR 57746A treatment. In the sciatic crush model, sensorimotor function improved more rapidly in rats treated with 10 mg/kg SR 57746A. In this same model, SR 57746A (10 mg/kg/day) also significantly increased the length of regenerated nerve eight days after the crush, as measured using the pinch test. Finally, SR 57746A retarded the onset, reduced the amplitude and accelerated the recovery of acrylamide-induced peripheral neuropathy. Thus, SR 57746A possesses notable neurotrophic activity in a variety of neurodegenerative models in vivo, suggesting that the compound may possess therapeutic potential for the treatment of neurodegenerative diseases.

Acetylcholinesterase↗