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Chantal Mathieu

Publications and source records attributed to Chantal Mathieu.

At least 73 records · Page 4Linked to original sources
PubMed2003

Progesterone in gestational diabetes mellitus: guilty or not guilty?

Insulin resistance is one of the metabolic changes in pregnancy, but only a fraction of women develop overt impaired glucose tolerance or frank diabetes. Most women are able to compensate this altered metabolic state by increasing the amount of insulin produced by the pancreatic beta cells. Progesterone might well be the key to the development of gestational diabetes. Previously high progesterone levels have already been shown to be correlated with the development of glucose abnormalities in pregnancy and now, in a new paper, progesterone receptor-knockout mice are found to have improved glucose tolerance. These mice showed increased insulin secretion, which is probably linked to the presence of increased numbers of beta cells in their pancreas. Is progesterone therefore the 'ultimate bad guy', prohibiting normal adaptation of the pancreatic beta-cell reserve during pregnancy?

Animals↗
PubMed2003

Amplification of Nicotiana sylvestris mitochondrial subgenomes is under nuclear control and is associated with phenotypic changes.

We have previously shown the presence in a Nicotiana sylvestris protoplast-derived plant of both a nuclear mutation conferring male sterility (ms4) and a mtDNA reorganisation, named U, characterised by the amplification of substoichiometric mtDNA fragments generated by recombination in the parent T mtDNA. Here we show by physical mapping that the recombining repeats are in direct orientation, thus generating two subgenomes both of which are amplified in the U organisation to the detriment of the parent molecule, and are maintained through sexual reproduction. The nuclear ms4 mutation is likely to have play a role in the shift in mitochondrial molecule equilibrium, as higher levels of recombinant fragments were present in protoplast-derived T calli carrying the ms4 allele than in wild type calli or leaves. The MS4 gene could then lead to conflictual situation. However, subgenomic molecules were counter-selected during the regeneration process, suggesting the existence of different selective pressures in differentiated and non-differentiated cells. The U organisation is associated with higher stem height and late flowering, characters that may not be neutral from a selection point of view. The U equilibrium is an unusual example of sudden mtDNA reorganisation, without obvious differences in genetic information and with only a limited phenotypic impact.

Cell Nucleus↗
PubMed2003

Leaf mitochondria modulate whole cell redox homeostasis, set antioxidant capacity, and determine stress resistance through altered signaling and diurnal regulation.

To explore the role of plant mitochondria in the regulation of cellular redox homeostasis and stress resistance, we exploited a Nicotiana sylvestris mitochondrial mutant. The cytoplasmic male-sterile mutant (CMSII) is impaired in complex I function and displays enhanced nonphosphorylating rotenone-insensitive [NAD(P)H dehydrogenases] and cyanide-insensitive (alternative oxidase) respiration. Loss of complex I function is not associated with increased oxidative stress, as shown by decreased leaf H(2)O(2) and the maintenance of glutathione and ascorbate content and redox state. However, the expression and activity of several antioxidant enzymes are modified in CMSII. In particular, diurnal patterns of alternative oxidase expression are lost, the relative importance of the different catalase isoforms is modified, and the transcripts, protein, and activity of cytosolic ascorbate peroxidase are enhanced markedly. Thus, loss of complex I function reveals effective antioxidant crosstalk and acclimation between the mitochondria and other organelles to maintain whole cell redox balance. This reorchestration of the cellular antioxidative system is associated with higher tolerance to ozone and Tobacco mosaic virus.

Adaptation, Physiological↗
PubMed2003

Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma.

Interleukin (IL)-17 is produced by activated memory CD4(+) cells and induces cytokines and chemokines that stimulate neutrophil generation and recruitment. Here, we investigated the involvement of IL-17 in the bronchial influx of neutrophils in experimental allergic asthma. Inhalation of nebulized ovalbumin (OVA) by sensitized mice with bronchial eosinophilic inflammation resulting from chronic OVA exposure induced early IL-17 mRNA expression in inflamed lung tissue, concomitant with a prominent bronchial neutrophilic influx. Anti-IL-17 monoclonal antibodies (mAb) injected before allergen inhalation strongly reduced bronchial neutrophilic influx, in a manner equally as potent as the anti-inflammatory dexamethasone. Remarkably, anti-IL-17 mAb significantly enhanced IL-5 levels in both BAL fluid and serum, and aggravated allergen-induced bronchial eosinophilia. In another series of experiments, anti-IL-17 mAb were given repeatedly during the inhalatory challenge phase with OVA of sensitized mice. This treatment regimen abated bronchial neutrophilia in parallel with reduction of bone marrow and blood neutrophilia. In addition, anti-IL-17 mAb treatment elevated eosinophil counts in the bone marrow and bronchial IL-5 production, without alteration of allergen-induced bronchial hyperresponsiveness. In summary, our results demonstrate that IL-17 expression in airways is upregulated upon allergen inhalation, and constitutes the link between allergen-induced T cell activation and neutrophilic influx. Because neutrophils may be important in airway remodeling in chronic severe asthma, targeting IL-17 may hold therapeutic potential in human asthma.

Administration, Inhalation↗
PubMed2003

Hen egg white lysozyme vaccination induces acute shock in NOD mice.

To investigate whether vaccination could induce lethal shock and which mechanisms are involved in this phenomenon, we tested a panel of autoantigens or diabetes-irrelevant peptides or proteins in nonobese diabetic (NOD), Balb/c, and C57Bl/6 mice. Of the antigens tested, only nondiabetogenic hen egg white lysozyme induced a severe form of shock exclusively in NOD mice. The mechanism involved is suggestive of a Th(2)-mediated anaphylactic reaction possibly connected to activation of PAF and triggering of DIC.

Animals↗
PubMed2003

Acute shock induced by antigen vaccination in NOD mice.

Type 1 diabetes in NOD mice can be prevented through autoantigen vaccination by shifting lymphocyte differentiation toward a T-helper 2 (Th(2)) response. However, in other models of autoimmunity, this approach may be accompanied by unexpected triggering of Th(2)-dependent anaphylactic shock. To test the safety of vaccination therapy in the NOD mouse model, we evaluated the effects of immunization with a wide battery of antigens in NOD, BALB/c, and C57BL/6 mice. Surprisingly, a nondiabetogenic antigen, hen egg white lysozyme, induced severe shock exclusively in NOD mice (shock in 11 of 11 mice, lethal in 3 mice). Shock severity was further increased by a more pronounced Th(2) setting generated by 1alpha,25(OH)(2)D(3) administration (17 of 17 mice, lethal in 14 mice, P < 0.0001). Pretreatment with dexamethasone resulted in full rescue, indicating an immune-mediated mechanism. Serum IgE levels and Th(1)/Th(2) cytokine profile analysis showed that the shock phenomenon was paralleled by a Th(2) response. mRNA expression of platelet-activating factor receptor (PAF-R) was significantly higher in NOD mice (P < 0.01) and was further increased by 1alpha,25(OH)(2)D(3). Pretreatment with WEB2086 (PAF-R antagonist) again protected all mice from lethal shock, indicating PAF as an anaphylaxis effector. In conclusion, in NOD mice, vaccination leading to a Th(2) immune shift can result in a lethal anaphylactic reaction.

Animals↗
PubMed2003

Prevalence and predictors of sexual dysfunction in patients with type 1 diabetes.

OBJECTIVE: This study aimed to 1) measure the prevalence of sexual dysfunction in patients with diabetes; 2) describe how descriptive variables, psychological variables, diabetic complications, and sexual dysfunction relate in patients with diabetes; and 3) describe the predictors of sexual dysfunction in patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 240 adult type 1 diabetic patients visiting the outpatient diabetes clinic of a university hospital completed questionnaires evaluating psychological adjustment to diabetes and sexual functioning. Medical records were used to obtain HbA(1c) values as well as information on microvascular diabetic complications. RESULTS: Sexual dysfunction was reported by 27% of women and 22% of men. No differences were found between sexes in type of reported sexual dysfunction. In men, but not in women, sexual dysfunction was related to age, BMI, duration of diabetes, and diabetic complications. No correlation with HbA(1c) was found in either sex. In women, but not in men, sexual dysfunction was related to depression and the quality of the partner relationship. Binary logistic regression demonstrated that, in men, the significant predictors of sexual dysfunction were higher age and presence of complications, whereas, in women, sexual dysfunction was related to depression. CONCLUSIONS: Both women and men with diabetes are at increased risk for sexual dysfunction. This study suggests that in men with diabetes, sexual dysfunction is related to somatic and psychological factors, whereas in women with diabetes, psychological factors are more predominant.

Adult↗
PubMed2002

Blockade of CTLA-4 enhances allergic sensitization and eosinophilic airway inflammation in genetically predisposed mice.

CTLA-4 (CD152) expression is restricted to subsets of activated T lymphocytes and shares homology with CD28. CTLA-4 and CD28 molecules both bind to B7 molecules on antigen-presenting cells. Whereas CD28-B7 interaction enhances T cell activation, cytokine production and survival, CTLA-4 signaling down-regulates T cell responses. Here, we studied the involvement of CTLA-4 triggering in the pathogenesis of allergen-induced airway inflammation in mice. Anti-CTLA-4 mAb were injected during i.p. sensitization with ovalbumin (OVA). This treatment favored OVA-specific IgE production and augmented blood eosinophilia in BALB/c mice. In BALB/c mice, enhanced Th2 sensitization after anti-CTLA-4 mAb injections resulted in more severe airway inflammation, and increased airway hyperresponsiveness to metacholine, bronchial eosinophilia and IL-4 and IL-5 levels in broncho-alveolar lavage (BAL) fluid following repeated allergen inhalations. Importantly, aggravation of airway inflammation and enhancement of Th2 responses were accompanied by a significant reduction of pulmonary TGF-beta levels at protein level in BAL fluid as well as on mRNA level in inflamed lung tissue. In contrast to BALB/c mice, blockade of CTLA-4 did not alter IgE production nor the phenotype of airway inflammation or TGF-beta production in C57BL/6 mice. Our data suggest that CTLA-4 triggering represents an important regulatory mechanism for Th2 sensitization in genetically predisposed mice by modulating TGF-beta production.

Abatacept↗
PubMed2002

The coming of age of 1,25-dihydroxyvitamin D(3) analogs as immunomodulatory agents.

The active form of vitamin D, 1,25-dihydroxyvitamin D(3)[1,25(OH)(2)D(3)], is a secosteroid hormone that regulates calcium and bone metabolism, controls cell proliferation and differentiation, and exerts immunoregulatory activities. This range of functions has been exploited clinically to treat a variety of conditions, from secondary hyperparathyroidism to osteoporosis, to autoimmune diseases such as psoriasis. Recent advances in understanding 1,25(OH)(2)D(3) functions and novel insights into the mechanisms of its immunomodulatory properties suggest a wider applicability of this hormone in the treatment of autoimmune diseases and allograft rejection.

Adjuvants, Immunologic↗
PubMed2002

An uncommon tumor in a renal graft recipient: a diagnostic and therapeutic challenge.

The development of malignancies after solid organ transplantation represents an increasing clinical problem complicating the long-term follow-up of transplant recipients. In this case report the authors describe the rare triple combination of a simultaneous hepatocellular carcinoma with a glucagonoma and a splenic hamartoma in a renal allograft recipient. It is not only the first published report of a glucagonoma occurring after renal transplantation but serves also as an illustration of the therapeutic decision making in the setting of the immune-compromised host. This case report also illustrates the different imaging modalities that can be used for the diagnosis of neuroendocrine tumors.

Carcinoma, Hepatocellular↗
PubMed2002

1,25-dihydroxycholecalciferol: endocrinology meets the immune system.

Previous work has demonstrated that, besides its effects on Ca and bone metabolism, the active form of cholecalciferol, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), possesses pronounced immunomodulatory effects. In non-obese diabetic (NOD) mice primary (before disease onset), secondary (after insulitis but before diabetes onset) as well as tertiary (after transplantation of syngeneic islets) prevention of diabetes was demonstrated with 1,25(OH)2D3 and its chemically-manufactured non-hypercalcaemic analogues. 1,25(OH)2D3 exerts its immune effects both at the level of the T lymphocyte (shift in cytokine profile from T-helper (Th)1 to Th2, enhanced sensitivity to apoptosis-inducing signals) as well as at the level of the antigen-presenting cell (reduced antigen presentation, reduced production of Th1-promoting cytokines, reduced expression of co-stimulatory molecules). Also, physiologically, 1,25(OH)2D3 is believed to have a role in the immune system by serving as a negative feedback signal, limiting the mounted immune reaction. To test the clinical applicability of 1,25(OH)2D3 as treatment for type 1 diabetes in genetically-at-risk young children, we tested whether short-term early-life intervention with cholecalciferol or non-hypercalcaemic analogues of 1,25(OH)2D3 could prevent diabetes in NOD mice. Significant protection of pancreatic beta cells against autoimmune destruction was observed in analogue-treated and especially in cholecalciferol-treated NOD mice as compared with controls (P<0.005). This short-term early-life intervention was, however, not able to protect the mice from developing diabetes during their lifetime. Possible solutions are longer or combined treatments with other immunomodulators that have synergistic effects with 1,25(OH)2D3 and its analogues.

Animals↗
PubMed2002

A view on beta cell transplantation in diabetes.

Organ donors also offer a source of insulin-producing tissue that might be used for the treatment of diabetes. Clinical protocols for transplantation of this tissue aim for the prevention of chronic diabetes complications without introducing new serious side effects. Pancreas and islet cell transplantation are discussed in this perspective. The future of islet cell implants looks favorable but depends on finding ways to induce immune tolerance to the donor beta cells. Clinical trials can take advantage of relevant progress in animal models. In a limited study, recipient treatment with antilymphocyte antibodies and culture of donor cell preparations appeared useful to induce a state of operational immune tolerance in type 1 diabetic patients, as indirectly judged by graft survival and by analysis of auto- and alloreactivities in recipients. Use of cultured beta cell preparations also allows donor cell recruitment from suboptimal donor organs and increases the degree of standardization and quality control of islet cell grafts. The future of these grafts will depend on the development of techniques for the neogenesis of beta cells.

Animals↗
PubMed2002

Relation between disease phenotype and HLA-DQ genotype in diabetic patients diagnosed in early adulthood.

We investigated inaugural disease phenotype in relation to the presence or absence of diabetes-associated autoantibodies and human leukocyte antigen (HLA) DQ risk genotypes in adult-onset diabetic patients. Blood samples and questionnaires were obtained from 1584 recent-onset Belgian Caucasian patients (age 15-39 yr at diagnosis of primary diabetes) who were recruited by the Belgian Diabetes Registry over an 11-yr period. At clinical diagnosis, antibody-positive patients (n = 1198) were on average younger and had more symptoms, a more acute disease onset, lower body mass index, and random C-peptide levels, but higher insulin needs, glycemia, and prevalence of ketonuria, HLA-DQ, and 5' insulin gene susceptibility genotypes (P < 0.001 vs. antibody-negative patients; n = 386). In antibody-positive patients, these characteristics did not differ according to HLA-DQ genotype. However, in antibody-negative subjects, we found that patients were younger (P = 0.001); had a lower body mass index (P < 0.001), higher insulin needs (P = 0.014), and amylasemia (P = 0.001); and tended to have a higher glycemia and lower C-peptide in the presence of susceptible HLA-DQ genotypes. Differences according to HLA-DQ genotype subsisted after careful age-matching. In conclusion, we found no relation between initial disease phenotype and HLA-DQ genotype in antibody-positive diabetic young adults. In contrast, antibody-negative patients displayed more type 1-like features when carrying susceptible HLA-DQ genotypes known to promote the development of antibody-positive diabetes. The overrepresentation of these susceptibility genotypes in antibody-negative patients suggests the existence of an immune-mediated disease process with as yet unidentified immune markers in a subgroup of seronegative patients.

Adolescent↗
PubMed2002

Redirection of human autoreactive T-cells Upon interaction with dendritic cells modulated by TX527, an analog of 1,25 dihydroxyvitamin D(3).

The active form of vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), is a potent immunomodulator known to affect T-cells through targeting antigen-presenting cells such as dendritic cells (DCs). We studied the effects of a novel nonhypercalcemic 1,25(OH)(2)D(3) analog, TX527, on DC differentiation, maturation, and function with respect to stimulation of a committed human GAD65-specific autoreactive T-cell clone. Continuous addition of TX527 impaired interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF)-driven DC differentiation as well as lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-induced maturation into Th1-promoting DC (DC1), as characterized by marked changes in DC morphology and abrogation of IL-12p70 release upon CD40 ligation. Addition of TX527 during maturation did not affect DC morphology but significantly changed DC cytokine profiles. The potential of treated DCs to alter the response pattern of committed autoreactive T-cells was found to depend on the timing of TX527 exposure. Continuously TX527-treated DCs significantly inhibited T-cell proliferation and blocked IFN-gamma, IL-10, but not IL-13 production, whereas DCs treated during maturation failed to inhibit T-cell proliferation but affected IL-10 and IFN-gamma production. Collectively, we provide evidence that nonhypercalcemic TX527 is a potent in vitro DC modulator, yielding DCs with the potential to change cytokine responses of committed autoreactive T-cells.

Alkynes↗
PubMed2002

The influence of maternal BMI and age in twin pregnancies on insulin resistance in the offspring.

OBJECTIVE: There is strong evidence that low birth weight is associated with glucose intolerance and diabetes in adults. We have carried out a twin study to distinguish among maternal influences, which affect both twins; fetoplacental influences, which are unique to each twin; and the genetic factors that may underlie this association. RESEARCH DESIGN AND METHODS: We identified a sample of 423 twin pairs (250 monozygotic and 173 dizygotic) from the East Flanders Prospective Twin Survey who were born between 1964 and 1982. Data collected in this study included the mother's body composition and weight gain during pregnancy, the twins' birth weights, and gestational age. The twins (aged 18-34 years) attended a research center for measurement of height, weight, and waist-to-hip ratio as well as fasting glucose, proinsulin, and insulin concentrations. RESULTS: Among twin pairs discordant for birth weight, we found little evidence that the lighter twin had abnormal glucose-insulin metabolism in adult life. However, both a low prepregnancy maternal BMI and older maternal age at delivery were associated with hyperinsulinemia and evidence of insulin resistance in the offspring. Fasting insulin increased by 1.3% (95% CI 0.1-2.6%) per unit fall in maternal BMI and by 1.1% (0.02-2.0%) per year increase in maternal age. These associations were independent of the twins' BMI and waist-to-hip ratio and their zygosity. CONCLUSIONS: These novel findings suggest that in twin pregnancies, maternal factors are more important than fetoplacental factors in determining glucose-insulin metabolism in the offspring.

Adult↗
PubMed2002

Sexual dysfunction in women with type 1 diabetes: a controlled study.

OBJECTIVE: This study aimed to 1) examine the prevalence of sexual problems in women with type 1 diabetes, 2) compare this prevalence rate with that of an age-matched control group, 3) study the influence of diabetes-related somatic factors on female sexuality, and 4) study the influence of psychological variables on the sexual functioning of both groups. RESEARCH DESIGN AND METHODS: A total of 120 women with diabetes visiting the outpatient diabetes clinic completed questionnaires evaluating psychological adjustment to diabetes, marital satisfaction, depression, and sexual functioning. Medical records were used to obtain data on HbA(1c), use of medication, BMI, and early-onset microvascular complications. An age-matched control group of 180 healthy women attending an outpatient gynecological clinic for preventive routine gynecological assessment also completed the non-diabetes-related questionnaires. RESULTS: More women with diabetes than control subjects reported sexual dysfunction (27 vs. 15%; P = 0.04), but a significant difference was found only for decreased lubrication. No association was found between sexual dysfunction and age, BMI, duration of diabetes, HbA(1c), use of medication, menopausal status, or complications. Women with more complications, however, reported significantly more sexual dysfunctions, and the presence of complications altered treatment satisfaction. Both diabetic and control women with sexual dysfunction mentioned lower overall quality of the marital relation and more depressive symptoms than their respective counterparts without sexual problems. Depression was a significant predictor for sexual dysfunction in both women with diabetes and control subjects. CONCLUSIONS: Sexual problems are frequent in women with diabetes. They affect the overall quality of life and deserve more attention in clinical practice and research.

Adult↗