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C Fournier

Publications and source records attributed to C Fournier.

At least 91 records · Page 5Linked to original sources
PubMed1997

High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors.

Collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis, is induced in DBA/1 (H-2q) mice following immunization with type II collagen (CII) in CFA. Since we have previously shown that IFN-gamma exerts a biphasic effect during the evolution of CIA in DBA/1 mice, we analyzed the development of this disease in mice with a disruption of the IFN-gamma receptor gene (IFN-gammaR(0/0)). Mutant mice were interbred with the DBA/1 strain to yield IFN-gammaR(0/0) mice expressing the H-2q haplotype. In three consecutive experiments, IFN-gammaR(0/0) male mice were found to exhibit severe clinical and histologic arthritis with an average incidence of 88.5 vs 94.1% for the wild DBA/1 strain. Notably, onset of clinical symptoms occurred significantly earlier than in DBA/1 mice. Although of a lower magnitude than in males, CIA also developed early in IFN-gammaR(0/0) female mice and with higher clinical severity than in control DBA/1 females. Immunization of knockout mice with CII resulted in the generation of CII-specific T cells belonging to the Th1 phenotype that recognize the same immunodominant peptides as do DBA/1 mice. CIA in IFN-gammaR(0/0) mice was associated with a down-regulation of the CII-specific IgG response, and this impairment was essentially due to a strong reduction of Abs of the IgG2a isotype. Taken together, our findings provide evidence that IFN-gammaR deficiency in DBA/1 mice leads to the occurrence of severe CIA with an accelerated onset compared with that in wild-type mice, indicating that the proinflammatory action of IFN-gamma has been bypassed in the IFN-gammaR(0/0) mice.

Animals↗
PubMed1997

Conversion in vivo from an early dominant Th0/Th1 response to a Th2 phenotype during the development of collagen-induced arthritis.

Over the past decade, the central role of T cells in the process of collagen-induced arthritis (CIA) has been extensively documented. The inflammatory features of CIA and its successful modulation after treatment in vivo with Th2 lymphokines, known to down-regulate proinflammatory cytokines, classify CIA as a Th1-mediated disease. However, no direct evidence for the presence of the different T helper subsets has been obtained. To identify the collagen-specific CD4+ T cell subset(s) developing during the course of CIA, lymph nodes from susceptible DBA/1 mice (H-2q) were harvested at different times after injection of bovine type II collagen in Freund's complete adjuvant and checked by enzyme-linked immunospot assay for the production of interferon (IFN)-gamma and interleukin (IL)-4. The results clearly showed that type II collagen-specific T cells secreting either IFN-gamma, IL-4, or both, develop early in vivo, before the onset of arthritis: the number of IFN-gamma-secreting cells was already maximal 15 days after immunization, whereas more IL-4-secreting cells were found at day 30, just before the onset of clinical arthritis. Another strategy was to establish collagen-specific CD4+ T cell lines and sublines in vitro and to analyze their lymphokine secretion pattern. Lines generated 8 days after immunization displayed a mixed lymphokine secretion pattern characteristic of Th0 cells or of a mixture of Th1 and Th2 cells. After limiting dilution of a day 8 line, 60% of the growing sublines were Th0-like (secreting IFN-gamma, IL-4, and IL-5), and 25% were Th1 (secreting IFN-gamma). By day 25 post-immunization, 33% of the generated sublines were Th0-like, 11% Th1, and 56% Th2 (secreting IL-4 and IL-5). Moreover, all the sublines raised from the lymph nodes of arthritic mice harvested at day 55 secreted high amounts of Th2 lymphokines, and only 3 out of 14 also produced some IFN-gamma. This study demonstrates that during the course of CIA the collagen-specific CD4+ T cell response shifts in vivo from a dominant Th0/Th1 response to a clear Th2 phenotype. These results contribute to our understanding of the collagen-specific CD4+ T helper subsets which develop during the induction and clinical phases of CIA.

Animals↗
PubMed1997

Right and left isovolumic ventricular relaxation time intervals compared in patients by means of a single-pulsed Doppler method.

Right and left isovolumic ventricular relaxation time intervals measurements were obtained as follows: from the peak R wave on the electrocardiogram to either the mitral or the tricuspid pulsed Doppler flow trace onset minus the R to end-ejection zero flow crossing of the subaortic (left side) or pulmonary (right side) D flow trace time interval. A ratio was calculated as a percent difference duration between both isovolumic ventricular relaxation time intervals. The aim was to compare isovolumic ventricular relaxation time interval values in 42 healthy controls and to study the changes induced by heart diseases in 27 patients with (1) controlled hypertension without left ventricular hypertrophy, (2) hypertrophic cardiomyopathy, and (3) Cor pulmonale. Mean values of isovolumic ventricular relaxation time intervals significantly differed at paired and unpaired studies, with right isovolumic ventricular relaxation time intervals shorter than those of the left side in all groups (p < 0.001) except for patients with Cor pulmonale. Isovolumic ventricular relaxation time intervals did not correlate with heart rate and moderately correlated with left ventricular mass and age. No significant difference was found between healthy controls and patients with controlled hypertension. Significant changes were found in patients with hypertrophic cardiomyopathy and Cor pulmonale versus healthy controls for both isovolumic ventricular relaxation time intervals. However, significant changes in the ratio were only found in patients with Cor pulmonale (p < 0.005) because of abnormal similar values for both isovolumic ventricular relaxation time intervals. This Doppler method enabled, for the first time, serial comparison of isovolumic ventricular relaxation time intervals with a homologous method. Both isovolumic ventricular relaxation time intervals significantly lengthened with age and with left ventricular indexed mass, but their ratio remained insignificantly changed except for patients with Cor pulmonale. The concomitant right and left isovolumic ventricular relaxation time intervals lengthening in patients with hypertrophic cardiomyopathy and Cor pulmonale suggests interdependence of both ventricles through the septum. This makes recommendable systematic comparison of both sides. The calculation of a ratio, free from the effect of factors intervening on isovolumic ventricular relaxation time intervals, may, in addition, be of diagnostic help.

Adolescent↗
PubMed1997

The diagnostic value of urinary Crosslaps and serum alkaline phosphatase in patients with prostate cancer.

OBJECTIVE: To determine whether the urinary excretion of Crosslaps and serum alkaline phosphatase (ALP) are useful bone markers in patients with prostate cancer. PATIENTS AND METHODS: The study included 112 patients, comprising 25 with benign prostatic hyperplasia and 87 with carcinoma of the prostate, 41 of whom had localized prostate cancer and 46 with bone metastases. In the last group, 16 were stable and 30 were in clinical progression. Prostate-specific antigen (PSA) and the bone markers serum bone ALP and urinary Crosslaps were determined on the same day. RESULTS: The rates of excretion of Crosslaps were significantly greater in patients with than in those without bone metastases. Only Crosslaps showed a significant difference between patients with stabilized metastatic disease and those with no bone involvement. Crosslaps had a higher specificity and positive predictive value than had PSA level in patients with bone metastases, and a higher sensitivity than bone ALP. CONCLUSION: These preliminary findings suggest that Crosslaps may be useful as an additional bone marker in patients with prostate cancer and may provide information of the metastatic spread to bone in these patients. Prospective studies with serial measurements of bone markers are currently underway to relate these results to the progression of disease and to evaluate the response to treatment of bone metastases.

Aged↗
PubMed1997

Selective increased presentation of type II collagen by leupeptin.

Type II collagen (CII) is an arthritogenic self antigen in DBA/1 (H-2q) mice. To analyze the intracellular processing of this fibrillar protein in the context of I-Aq molecules, we have generated hybrid antigen-presenting cells (APC) by fusion of B lymphoma (A20 and M12) cells with CII-primed spleen cells from DBA/1 mice. Efficient presentation of CII by these APC to specific T cell hybridomas required prior cleavage of the antigen and intracellular handling of the peptides. Inhibition of protein transport by brefeldin A prevented the presentation of CII peptides to T cell hybridomas, indicating that the intracellular presentation of CII was dependent on neo-synthesis of I-Aq molecules. In contrast, exposure of hybrid B lymphomas to leupeptin, a protease inhibitor, induced a dose-dependent increase of CII-specific T cell response, while abrogating the I-Aq-restricted presentation of ovalbumin. The enhancing effect of leupeptin was also observed when immune B cells were used as APC. In contrast, leupeptin inhibited the presentation of CII peptides by macrophages or total spleen cells. Pulse-chase analysis of metabolically labeled hybrid APC and immunoprecipitation with antibodies specific for class II molecules or invariant (li) chain revealed that leupeptin did not affect the li chain processing or the formation of stable class II dimers. The stimulatory effect of leupeptin observed on CII presentation suggests that leupeptin protects CII epitopes by interfering with proteases involved in the intracellular degradation of CII.

Animals↗
PubMed1997

Lipoprotein(a) isoforms display differences in affinity for plasminogen-like binding to human mononuclear cells.

Binding of lipoprotein(a) (Lp(a)) to membrane proteins of the monocyte-macrophage cell lineage may be an important event in atheroma formation. Since Lp(a) with distinct apolipoprotein(a) (apo(a)) isoforms may show differences in their affinity with regard to fibrin binding, the existence of such a functional behavior in the interaction of apo(a) in Lp(a) with these cells was explored using the monocytic cell line THP-1. Lp(a) preparations containing small size apo(a) isoforms (M(r) = 450,000 to 550,000) and high molecular mass isoforms (M(r) > or = 700,000) were purified from plasmas containing > 0.35 g/L of Lp(a) obtained from subjects (n = 14) with cardiovascular atherosclerotic disease. Binding of plasminogen to THP-1 cells was performed using the method of radioisotopic dilution. For binding of Lp(a) to cells, the THP-1 monocytic cells were incubated with varying concentrations of the different Lp(a) preparations; cells were then washed and the amount of Lp(a) bound was detected with a radiolabeled polyclonal antibody directed against apo(a). Binding due to kringle interactions with lysine residues was calculated by subtracting from the total bound the amount of Lp(a) bound (approximately 10%) in the presence of 6-aminohexanoic acid. Analysis of data with the Langmuir equation indicated identical and independent (non-interacting) sites and allowed evaluation of the Kd. Binding isotherms of small size isoforms showed saturation and a high affinity (Kd = 25.8 +/- 19 nmol/L) relative to that of plasminogen (Kd = 1750 +/- 760 nmol/L). A similar difference (Kd = 17.5 +/- 7.9 nmol/L versus Kd = 600 +/- 220 nmol/L) was found when binding experiments were performed with a fibrin surface. In contrast, binding isotherms of the high molecular mass isoforms did not show saturation at the highest Lp(a) concentrations used, thus indicating a lower affinity. In conclusion, these results show that apo(a) isoforms may display polymorphism-linked functional heterogeneity with regard to cell binding, which may explain the higher association with cardiovascular risk of small size isoforms. These qualitative differences in the binding of apo(a) isoforms to fibrin or cells may modulate the cardiovascular risk associated with high levels of Lp(a).

Adult↗
PubMed1997

Childhood/early adolescence-onset and adult-onset schizophrenia. Heterogeneity at the dopamine D3 receptor gene.

BACKGROUND: The dopamine D3 receptor gene (DRD3) is a meaningful candidate gene because it unifies the dopamine and the limbic hypotheses for schizophrenia. We tested for an allelic association between schizophrenia and the DRD3 Mscl alleles, hypothesising heterogeneity between childhood/early adolescence-onset schizophrenia (CO-SZ) and adult-onset schizophrenia (A-SZ). METHOD: The frequencies of the DRD3 alleles were compared between 70 DSM-III-R schizophrenics (35 CO-SZ and 35 A-SZ) and 79 controls. RESULTS: Compared with the controls, the subsample of A-SZ, but not CO-SZ, showed an over-proportion (P = 0.025) of allele 1. The association was not found in the total sample, combining the two subsamples. CONCLUSIONS: Consistently with former studies, our data suggest an aetiological heterogeneity between CO-SZ and A-SZ and a possible specificity of the excess of allele 1 to the familial form of schizophrenia and to schizophrenia with a better outcome.

Adolescent↗
PubMed1996

Collagen-induced arthritis in DBA/1 mice: cytokine gene activation following immunization with type II collagen.

Immunization of DBA/1 mice with bovine type II collagen (CII) in complete Freund's adjuvant (CFA) leads to collagen-induced arthritis as evidenced by joint inflammation. In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to demonstrate the activation of genes encoding for IL-2, IFN-gamma, and IL-10 in the lymph nodes from both CII-immunized and control CFA-immunized DBA/1 mice, at Days 10, 40, and 70 after immunization, in the absence of any IL-5 or IL-13 transcription. By quantitative RT-PCR, the levels of IFN-gamma mRNA in response to CII could not be quantitatively differentiated from the IFN-gamma transcribed in response to CFA alone. In the joints of CII-immunized mice, IL-1beta and IL-10 mRNA were found in the absence of IL-5 or IFN-gamma. Synovial IL-1beta and IL-10 were expressed most strongly at the time of clinical symptoms, 40 days after immunization. Together, these findings suggest that immunization with CII in CFA induces a type 1 response against the adjuvant, giving a cytokine environment which influences the T cells responding to CII to become type 1 T cells. This is manifested here by the appearance of gene activation in synovial tissue of collagen-immunized mice, but not in adjuvant-immunized control animals.

Animals↗
PubMed1996

Attenuation of collagen-induced arthritis in mice by treatment with vector cells engineered to secrete interleukin-13.

The anti-inflammatory effects of the recently identified cytokine interleukin (IL)-13 on collagen-induced arthritis (CIA) was explored and compared to those of IL-4 using systemic administration of these cytokines via two injections of xenogeneic vector cells transfected with a plasmid construct. CIA was induced in DBA/I mice by immunization with native bovine type II collagen (CII). Chinese hamster ovary (CHO) fibroblasts transfected with the mouse IL-13 or IL-4 genes were inoculated subcutaneously on days 10 and 25 post-priming with CII and mice were monitored for signs of arthritis by observers unaware of the status of the animal. Incidence and severity of CIA were significantly reduced in the groups of mice treated with IL-13 and IL-4 gene-transfected CHO cells compared to control groups receiving nontransfected cells. Expression of various cytokines in spleen cells from individual mice was assessed by quantitative reverse transcriptase-polymerase chain reaction at different times after immunization. Our data show that IL-13-induced suppression of CIA coincided with a decreased TNF-alpha mRNA expression in the spleen of treated animals. This may explain at least partially the anti-inflammatory effects of IL-13 in CIA. Thus, our results may have important implications for the clinical use of T helper (Th)1/TH2 modulatory cytokines as therapeutic agents in the treatment of autoimmune diseases.

Animals↗
PubMed1996

Does induction chemotherapy with a mitoxantrone/vinorelbine regimen allow a breast-conservative treatment in patients with operable locoregional breast cancer? A French Northern Oncology Group trial in 105 patients. French Northern Oncology Group.

BACKGROUND: In recent years, induction chemotherapy has been tested by several investigators in the management of operable breast cancer. PATIENTS AND METHODS: Our current study was aimed to evaluate, pragmatically, in patients (74 stage II and 30 stage III) whose treatment would have been mastectomy, the percentage of them in whom a conservative treatment can be performed if primarily treated with a mitoxantrone/vinorelbine regimen. RESULTS: 67/104 patients (64%; 95% CI: 55-74%) had a conservative treatment (lumpectomy: 54, radiation therapy: 12, radiation therapy then lumpectomy: 1) Neutropenia was the major dose-limiting side effect, with grade 3 or 4 neutropenia registered in 83% of patients and 53.3% of the 442 cycles. Overall, a grade 3 or 4 non hematologic side effect occurred in 19.8% of patients and in 9.1% of cycles. One toxic death was observed after 2 cycles in a patient with aplasia who developped septicemia. Seventy one per cent of the patients experienced nausea and vomiting but grade 3 were observed in only 12% of the patients. Other side effects, including stomatitis, asthenia, alopecia, and constipation, were generally mild and uncommon. CONCLUSIONS: This mitoxantrone/vinorelbine regimen is an efficient induction treatment with only neutropenia as a noticeable side effect. It allows 64% of conservative treatment in patients whose treatment would have been mastectomy.

Adult↗
PubMed1996

Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. I: nosology, sex and age of onset.

BACKGROUND: Little is known about the long-term outcome of schizophrenia that has its onset during childhood and early adolescence (early-onset schizophrenia, or EO-SZ). Whether or not EO-SZ is an aetiologically separate form of schizophrenia (SZ) is unresolved. METHOD: The study was a 14.8-year follow-up, using methods such as systematic sampling, evaluation of possible non-respondent bias, consensus best-estimate diagnoses (DSM-III-R) made independently in childhood and adulthood, measures of positive and negative dimensions, of non-psychotic behaviour disturbances (NPBD) and of developmental problems before the appearance of SZ. RESULTS: There was high stability of EO-SZ (n = 40) diagnoses (mean onset at 14.0 years) until adulthood (mean age at follow-up 28.8 years) but a lower stability of positive and negative schizophrenic dimensions. There was a poor outcome of EO-SZ, a strong over-representation of males but few gender differences, and no effect of age of onset on clinical features and outcome. CONCLUSIONS: EO-SZ taken as a whole shows no qualitative differences to adult-onset SZ. However, a distinction through the onset of preschizophrenic developmental problems or NPBD might be a way to investigate heterogeneity within EO-SZ.

Adolescent↗
PubMed1996

Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. II: Postnegative distinction and childhood predictors of adult outcome.

BACKGROUND: The aim of this study was to verify the presence and stability across life of the positive/negative distinction in early-onset schizophrenia (EO-SZ) through a longitudinal factor analysis of the schizophrenic dimensions, and to identify the factors predicting several indices of long-term outcome for EO-SZ. METHOD: Forty children consecutively referred for DSM-III-R schizophrenia (SZ) in a specific catchment area comprised the sample. RESULTS: Across a 14.8-year follow-up, longitudinal factor analysis identified two separate factors corresponding to the positive and negative symptom dimensions. We also observed that: the GAS rated over the last three years of adult illness and the severity of negative symptoms during the stabilised interepisode intervals in adulthood were the indices of adult outcome that were most easily predicted; and the best childhood predictors of adult outcome were premorbid functioning and severity of positive and negative symptoms during acute episodes. CONCLUSIONS: The presence of premorbid non-psychotic behaviour disturbances (NPBD) and premorbid developmental problems was not related to severity of outcome, in contrast to the former variables.

Adolescent↗
PubMed1996

Overnight dexamethasone suppression test: comparison of plasma and salivary cortisol measurement for the screening of Cushing's syndrome.

The overnight 1-mg dexamethasone suppression test is a very good screening test for subjects suspected of having Cushing's syndrome. To simplify the procedure, we evaluated the 1-mg dexamethasone suppression test with measurement of salivary cortisol. We performed this test with plasma and salivary cortisol measurements in 27 patients with Cushing's syndrome and 64 normal controls. The sensitivity and specificity of plasma cortisol measurements were 100% and 87%, respectively, for a cut-off point of 100 nmol/l, in accordance with previous studies. The results of salivary cortisol showed the absence of overlap between the two groups, with a sensitivity and specificity of 100% for a cut-off point of 2.8 nmol/l. On a larger series, however, one might occasionally miss the diagnosis of a patient with Cushing's syndrome. Therefore, we favor a cut-off point of 1.9 nmol/l, the sensitivity remaining at 100% and the specificity being 94%. In conclusion we recommend the overnight dexamethasone suppression test with measurement of salivary cortisol as a screening test for Cushing's syndrome.

Adult↗
PubMed1996

[Predictive value of the hemogram for myelotoxicity induced by the association of carboplatin-fluorouracil on the 4th day of the therapeutic regimen].

The aim of this study was to determine the value of haematological counts at the 4th day of a chemotherapy cycle, in order to foresee neutro and/or thrombocytopenia during the same chemotherapy cycle. One hundred and ten cycles of chemotherapeutic regimens with carboplatin (400 mg/m2, dl) and 5-fluorouracile (1 g/m2/d, by iv continuous infusion for 96 hours) every 3 weeks, were analyzed for 42 patients with locally advanced but non metastatic squamous cell carcinoma of head and neck, without prior chemotherapy. Lymphocyte counts were significantly decreased at the 4th day but normalized at the 8th day (P < 10(-6)). Decreases of lymphocyte and neutrophil counts at the 4th day were significantly correlated to grade > 2 neutropenia. The positive predictive value of lymphocyte or neutrophil counts is about 50% for some cut-off values but not high enough, with the schedule of chemotherapy in our study, to justify the systematic prophylactic therapy with haematopoietic growth factors.

Adult↗
PubMed1996

[Experimental gene therapy in models of inflammatory arthritis].

Gene therapy is rheumatoid arthritis is presently in an experimental phase. Genes encoding for antiinflammatory proteins can be transfected in joint cells. Therefore gene encoding for interleukin-1 receptor antagonist has been transfected into synovial cells or into chondrocytes. Gene expression can be maintained as long as 8 weeks after cell transfer. We have reported that clinical and histopathological parameters of collagen-induced arthritis (an animal model of rheumatoid arthritis) can be reduced by engraftment of CHO cells transfected with genes encoding for antiinflammatory cytokines such as interleukine-4 or interleukine-13. Some of the questions which need to be assessed before planning clinical trial are the choice of vectors and the most efficient target cells; and the genes to be transfected have to be chosen among many candidates.

Animals↗
PubMed1996

[Attitudes towards screening and prevention of breast and ovarian cancers with hereditary predisposition. Survey by female gynecologists in the north of France].

Search for mutations of BRCA1 in women at hereditary risk for cancer is now possible. We asked the female gynaecologists of our county (north of France) their opinion about the search of a mutation of BRCA1 if they had a familial risk of breast cancer. Our aim was to obtain the opinion of informed women about their willingness to do the test for themselves and about the consequences they should accept. One hundred and eighty-three women received a questionnaire by post. The response rate was 56.3%. Twenty-four percent of the responders had a first degree relative with breast cancer. Most of the responders (87.4%; IC 95%: 81-93.8) would ask for the search of a mutation of BRCA1. The percentage of women who would accept the test is smaller for the women who have a first degree relative with breast cancer (72.0% vs 92.3%; P = 0.02). The reasons given to do the test were a better screening or prevention (69.7%) and the knowledge of a personal risk (49.4%). For breast cancer, 93.2% (95% CI: 88.4-98) would accept a screening protocol, 30.1% (CI: 21.3-38.9) would accept a prophylactic bilateral mastectomy. For ovarian cancer, 93.2% (CI: 88.4-98) would accept the screening, 52.4% (CI: 42.8-62) would accept a prophylactic ovariectomy. In conclusion, most of the informed women would ask for the test and the surgical options for reducing the risk of cancer are not absolutely rejected. Of course, only future studies will state precisely the choice of truly implicated women.

Adult↗