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C Mathieu

Publications and source records attributed to C Mathieu.

At least 37 records · Page 2Linked to original sources
PubMed2004

The effect of beam diameter on the electron skirt in a high pressure scanning electron microscope.

Helium gas and air are commonly used in the high pressure scanning electron microscope (HPSEM). The presence of a gaseous environment in the specimen chamber modifies the electron beam profile. In order to fully understand the beam-gas interaction, we have investigated the beam-diameter effect for two gases (helium and air) by Monte Carlo simulation. In this calculation, we have assumed that the electron beam is Gaussian and we have explored the influence of the nature of the gas at low voltage. When the beam diameter varies between 1 and 100 nm, there is no influence on the beam profile for these two gases. The resolving power of the HPSEM is not affected by the beam-gas interaction. These theoretical results have been compared with experimental images obtained at low voltage under air and helium gases. The variation of image quality at low voltage has confirmed the interest of helium for use in a Field Emission Gun SEM (FEGSEM) in high pressure (or low vacuum) conditions.

Journal Article↗
PubMed2004

Differential expression of the nm23 genes in the developing human trophoblast.

NDP kinases are the non-specific enzymes which catalyse the synthesis of the NTPs through a transfer reaction using ATP as phosphoryl donor. In addition to their enzymatic activity, they display other not yet explained functions related to cell growth, differentiation and apoptosis, embryonic development, tumour progression and metastasis. In this study, the expression patterns of the three highly related NDP kinases A, B and C isoforms were investigated in the developing human trophoblast. Both NDP kinase A and B were found to be primarily present in the villous and extravillous cytotrophoblasts, while NDP kinase C was found almost exclusively in the syncytiotrophoblast layer. This suggests that NDP kinase A and B could be a marker for the mononuclear stage of differentiation of villous trophoblasts, while NDP kinase C could be a marker of the syncytiotrophoblast layer.

Embryonic and Fetal Development↗
PubMed2004

Can we reduce hypoglycaemia with insulin detemir?

Tight glycaemic control is essential for reducing the risk of long-term diabetic complications in people with type I or II diabetes. Intensive blood-glucose control attempts to normalise both pre- and postprandial glycaemia, while avoiding severe hypoglycaemia. A basal insulin, providing a low level of insulin to cover postprandial and overnight fasting periods, is central to intensive blood-glucose control. However, hypoglycaemia, particularly nocturnal hypoglycaemia, is a major treatment-related complication of therapy with most basal insulins currently available for use in clinical practice. This is a result of pronounced peaks in absorption, which lead to inappropriate hyperinsulinaemia following evening administration, and especially poorly reproducible pharmacokinetic profiles when injected subcutaneously. Indeed, for many patients and health-care providers, concern around hypoglycaemia forms a critical barrier to the attainment of tight glycaemic control. Insulin detemir is a novel long-acting analogue of human insulin designed to overcome these practical limitations. Clinical evidence from comparative studies with NPH insulin shows that insulin detemir provides a consistent and clinically relevant reduction in hypoglycaemic risk, especially for nocturnal events, at equivalent or better levels of glycaemic control.

Blood Glucose↗
PubMed2004

Early up-regulation of Th2 cytokines and late surge of Th1 cytokines in an atopic dermatitis model.

We investigated cytokine profiles in interleukin (IL)-4 transgenic (Tg) mice with a skin inflammatory disease resembling human atopic dermatitis. cDNA microarray revealed that the mRNAs encoding IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-13, tumour necrosis factor (TNF)-alpha, TNF-beta and interferon (IFN)-gamma were up-regulated in the skin of late lesion Tg mice and to a lesser degree in non-lesion Tg mice when compared to those of non-Tg mice. Real time reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated that the cDNA copy numbers of IL-1beta, IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma from the skin of late, early and non-lesions increased significantly compared to non-Tg mice. IL-2 and IL-12p40 cDNA copy numbers were increased significantly in early, but not late, lesions. Interestingly, IL-1beta, IL-3, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-alpha, and IFN-gamma cDNAs were increased significantly the skin of before-onset and/or non-lesion mice. Flow cytometry analyses demonstrated an increased percentage of keratinocytes producing IL-4 as the disease progressed. The percentage of IL-2, IL-4, IL-10 and IFN-gamma-producing T cells and IL-12-producing antigen-presenting cells in skin-draining lymph nodes and inflammatory skin also increased, particularly in mice with late lesion. These results suggest that disease induction is primarily triggered by Th2 cytokines and that Th1, Th2 and non-Th proinflammatory cytokines are all involved in the disease process.

Animals↗
PubMed2003

Prevention of primary non-function of islet xenografts in autoimmune diabetic NOD mice by anti-inflammatory agents.

AIMS/HYPOTHESIS: High levels of inflammation locally in the graft during the initial days after transplantation can cause primary non-function (PNF) of grafted xenogeneic islets in NOD mice. The aim of this study was to explore in a model of spontaneous diabetes, the NOD mouse, the potential of anti-inflammatory agents in the prevention of PNF after xenogeneic islet transplantation. METHODS: Spontaneously diabetic NOD mice were transplanted with 300 rat islets. Animals were treated with acetylsalicylic acid (AsA), rofecoxib, TGF-beta or IL-1 receptor antagonist (IL-1ra). Intra-graft expression of inflammation-related molecules was measured by real time PCR 8 h post-transplantation. At the same time point, plasma nitrite levels were measured. RESULTS: Xenogeneic islets transplanted in control spontaneously diabetic mice resulted in PNF in 16 out of 38 mice (42%). Initial graft loss was not altered by administration of rofecoxib (30%) or TGF-beta (25%). AsA reduced the rate of rapid graft loss to 8% ( p<0.05 vs controls) and administration of IL-1ra even totally prevented PNF (0%, p<0.05 vs controls). Furthermore, all therapies prolonged the mean survival time of xenogeneic islet grafts. The inhibition of PNF by AsA was associated with decreased intra-islet levels of inflammation-related molecules (IL-1, TNF-alpha, iNOS, COX-2) and chemokines (MCP-1 and MIP-3alpha). Finally, also a diminished production of systemic nitrite levels was observed in AsA- and IL-1ra-treated islet recipients. CONCLUSIONS/INTERPRETATION: These data show that treatment with AsA or IL-1ra prevents PNF after islet transplantation in spontaneously diabetic NOD mice. Moreover, the involvement of non-specific inflammation is recognized in xenogeneic islet PNF in spontaneously diabetic NOD mice.

Animals↗
PubMed2003

IL-1beta and IFN-gamma induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice.

AIMS/HYPOTHESIS: Cytokines and chemokines are important mediators of immune responses due to their ability to recruit and activate leukocytes. Using microarray analysis we observed that rat beta cells exposed to IL-1beta and IFN-gamma have increased mRNA levels of chemokines and IL-15. The aim of this study was to characterize the expression of IP-10, MIP-3alpha, fractalkine and IL-15 in rat beta cells, human pancreatic islets, and in islets isolated from NOD mice, both during the pre-diabetic period and following islet transplantation. METHODS: FACS-purified rat beta cells and human islets were cultured with IL-1beta, IFN-gamma and/or TNF-alpha. Islets were isolated from NOD or BALB/c mice at different ages. For syngeneic islet transplantation, 2- or 3-week-old NOD islets were grafted under the kidney capsule of spontaneously diabetic NOD recipients. Chemokine and IL-15 mRNA expression and protein release were evaluated, respectively, by RT-PCR and ELISA. RESULTS: Human islets and rat beta cells express IP-10, MIP-3alpha, fractalkine and IL-15 mRNAs upon exposure to cytokines. The expression of IL-15, IP-10 and fractalkine is regulated by IFN-gamma, while the expression of MIP-3alpha is IL-1beta-dependent. Moreover, cytokines induced IL-15, IP-10, Mig, I-TAC and MIP-3alpha protein accumulation in culture medium from human islets. In vivo, there was an age-related increase in IL-15, IP-10 and MIP-3alpha expression in islets isolated from NOD mice. Following syngeneic islet transplantation, increased expression of IL-1beta, IFN-gamma, fractalkine, IP-10, MCP-1 and MIP-3alpha mRNAs were observed in the grafts. CONCLUSION/INTERPRETATION: Cytokine-exposed islets or beta cells express chemokines and IL-15. This could contribute to the recruitment and activation of mononuclear cells and development of insulitis in early Type 1 diabetes and during graft destruction.

Adult↗
PubMed2003

Break of tolerance via donor-specific blood transfusion by high doses of steroids: a differential effect after intestinal transplantation and heart transplantation.

UNLABELLED: Tolerance requires active mechanisms. How immunosuppressors affects tolerance is poorly understood. METHODS: RA (RT1(p))/PVG (RT1(c)) rats were used as donor/recipient. Intestinal and heart transplant model were selected as highly and poorly immunogenic organs. Studied groups were 1, rejecting control; 2, received peritransplant steroids; 3, donor-specific blood transfusion (DSBT); 4, DSBT plus peritransplant steroids; and 5, DSBT+periDSBT Ste. RESULTS: Intestinal transplant recipients in group 1 died on posttransplant day (d) 18. In group 2, steroids did not change survival (17 days, P >.05 versus group 1). With DSBT (group 3), all rats survived >75 days, whereas with steroids those in group 4 survived 59 days (P >.05 vs group 3) and group 5 survived 51 days (P <.05 versus group 3). Survivors in group 2 were tolerant as evidenced by acceptance of secondary donor-specific (not third-party) graft. However, 100% and 33% of donor-specific secondary grafts were rejected in groups 4 and 5 (P <.05 and P >.05 versus group 3). In heart transplants, steroid treatment had no effect on graft survival (group 1 9 days; group 2 9 days; P >.05). DSBT (group 3) induced 100% tolerance (primary: >100 days, secondary: 100%). Unlike in intestinal transplantation, adjunction peritransplant steroids (group 4) allowed 100% of primary and 83% of secondary graft acceptance (P >.05 versus group 3). In group 5, (DSBT+periDSBT steroids) acceptance of primary and secondary grafts tended to be reduced (primary: 77 days; P >.05 versus group 3; secondary: 67%, P >.05 versus group 3). CONCLUSION: Steroid induction did not prolong graft survival after either intestinal or heart transplant. Adjunction of steroids to a DSBT tolerogenic regimen caused rejection of primary and secondary grafts, particularly after intestinal transplantation. Routine use of steroids in the clinics must be reconsidered, particularly when immunogenic organs are transplanted and when immunomodulation is applied.

Animals↗
PubMed2003

Combination of a 1,25-dihydroxyvitamin D3 analog and a bisphosphonate prevents experimental autoimmune encephalomyelitis and preserves bone.

The vitamin D analog TX527 (19-nor-14,20-bis epi-23-yne-1,25(OH)(2)D(3)), decreased disease severity (P < 0.001) and postponed disease onset (P < 0.0001) in SJL mice in which experimental autoimmune encephalomyelitis was induced. Levels of IFN-gamma and IL-2 mRNA were decreased in spinal cord and spleen in the analog-treated mice, suggesting a Th(1)-targeted effect. Adding the bisphosphonate pamidronate did not affect analog-protective efficacy, but completely prevented TX527-caused acceleration of bone turnover and increased total bone mineral content as well as femoral mineral and calcium content (P < 0.01). Less calcemic analogs of 1,25-dihydroxyvitamin D(3), in combination with bone sparing products such as bisphosphonates allow immune modulation in vivo without affecting bone.

Animals↗
PubMed2003

Markers for cardiovascular disease in monozygotic twins discordant for the use of third-generation oral contraceptives.

Oral contraceptives (OC) modulate the risk for developing cardiovascular (CV) diseases. The aim of this study was to determine whether the use of third-generation OC has an impact on markers of CV disease in genetically identical women. We performed an intrapair comparison in 27 monozygotic twin pairs, one of whom was taking third-generation OC, whereas the other was not using OC. Biometric parameters were ascertained and conventional and 24-h ambulatory blood pressure (BP) was recorded. A fasting blood sample was taken for the measurement of glucose, insulin, proinsulin, lipids, and insulin-like growth factor binding protein-1 (IGFBP-1). Insulin resistance and beta-cell function were calculated by homeostasis model assessment (HOMA). A 24-h urine sample for cortisol was obtained. Third-generation OC use increased 24-h ambulatory systolic and diastolic BP by 5.2 and 3.9 mmHg, respectively (both P=0.0003). There was no effect on glucose, insulin and proinsulin levels, and on HOMA parameters, but the IGFBP-1 levels were markedly raised (P=0.0009). The lipid profile showed a 34% increase in triglyceride levels (P < 0.0001), but also a 7% increase in HDL-cholesterol levels (P=0.037). Use of third-generation OC impacts on CV disease markers in young-adult genetically identical women. Some changes are beneficial (increased HDL-cholesterol), whereas others may be deleterious (increased BP and triglyceride levels) or have unknown effects at this time (increased IGFBP-1 levels).

Adult↗
PubMed2003

Defective activation-induced cell death in NOD T lymphocytes: 1,25-dihydroxyvitamin D3 restores defect.

The aim of this study was first to analyze strain differences in apoptosis resistance of NOD peripheral T lymphocytes in in vitro models of death by neglect and activation-induced cell death (AICD). Especially AICD is known to play a key role in peripheral tolerance, keeping autoimmune effector cells under control. Second, we studied the effects of in vivo treatment of NOD mice with 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], an immunomodulator known to prevent diabetes and insulitis in NOD mice, on in vitro T lymphocyte apoptosis resistance.

Animals↗
PubMed2003

The use of real-time reverse transcriptase PCR for the quantification of cytokine gene expression.

Real-time reverse transcriptase polymerase chain reaction (RT-PCR) is becoming a widely used method to quantify cytokines from cells, tissues, or tissue biopsies. The method allows for the direct detection of PCR product during the exponential phase of the reaction, combining amplification and detection in a single step. Using TaqMan chemistry (Applied Biosystems, Foster City, CA) and the ABI Prism 7700 Sequence Detection System (Applied Biosystems), we validated a large panel of murine and human cytokines, as we as other factors playing a role in the immune system, such a chemokines and apoptotic markers. Although the method allows fast, sensitive, and accurate quantification, different control assays are necessary for the method to be reliable. By construction of complementary DNA (cDNA) plasmid clones, standard curves are generated that allow direct quantification of every unknown sample. Furthermore, the choice of a reliable housekeeping gene is very important. Finally, co-amplification of contaminating genomic DNA is avoided by designing sets of primers located in different exons or or intron-exon junctions. In conclusion, the real-time RT-PCF technique is very accurate and sensitive, allows high through put, and can be performed on very small samples. The development of real-time RT-PCR has resulted in an exponential increase in its use over the last couple of years, and the method has undoubtedly become the standard for quantifying cytokine patterns, clarifying many functional properties of immune cells and their associated diseases.

Animals↗
PubMed2003

[Is cheating with automatic perimetry possible?].

INTRODUCTION: Automatic perimetry examination requires the patient's cooperation, but the programs used check response validity. This study evaluated the possibility of patient cheating on this examination. MATERIALS AND METHOD: This study investigated 27 visual fields of automatic perimetry with patients who had no ophthalmological history. Each subject had to reproduce a visual field loss that was observed for 5 minutes (two diffuse losses, five fields reflecting hemianopsia, four reflecting quadranopsia, two tubular losses, five nasal steps, nine absolute and arciform losses). The 24-2 Fastpac of the Humphrey field analyzer and the G2 of the Octopus perimeter were used for this study. RESULTS: Simple deficits were easy to reproduce, but visual field defects are often deeper and simulated test results tend to be too perfect. On the other hand, complex defects such as arciform scotoma or nasal steps were more difficult to reproduce. Visual field defect simulations were exaggerated beyond what was reasonable. CONCLUSION: This study reports on whether it is possible to cheat with automatic perimetry. The different parameters analyzed by computer programs are not able to detect cheating patients.

Adult↗
PubMed2002

IA-2 autoantibodies predict impending type I diabetes in siblings of patients.

AIMS/HYPOTHESIS: Multiple islet autoantibody positivity is currently believed to best predict progression to Type I (insulin-dependent) diabetes mellitus. We compared its predictive value with that of positivity for a particular type of islet autoantibody, directed against the IA-2 antigen. METHODS: Autoantibodies against islet cell cytoplasm (ICA), insulin (IAA), GAD (GADA) and IA-2 (IA-2A) were measured at initial sampling in 1724 non-diabetic siblings (median age [range]:16 [0-39] years) of Type I diabetic patients with a median follow-up of 50 months. RESULTS: On initial sampling 11% of siblings were positive for one antibody type or more and 2.1% for three of more types. During follow-up, 27 antibody-positive siblings developed diabetes. Using survival analysis, the risk for clinical onset within 5 years was 34% in subjects positive for three or more types compared with 13% in those with one type or more. Progression to diabetes amounted to 12% within 5 years among siblings positive for IAA, 20% for ICA, 19% for GADA but 59% for IA-2A (p<0.001 vs absence of the respective antibody). IA-2A were detected in 1.7% of all siblings and in 56% of the prediabetic subjects on first sampling. Initial positivity for two or three antibody markers was associated with a higher progression rate in IA-2A positive as compared to IA-2A negative siblings (p=0.001). In absence of IA-2A initial positivity for another antibody (IAA, ICA or GADA) conferred a low (<10% within 5 years) risk of diabetes compared to subjects lacking this antibody. CONCLUSIONS/INTERPRETATION: In siblings of Type I diabetic patients, IA-2A positivity is a more direct predictor of impending clinical onset than multiple antibody positivity per se. Assessment of IA-2A status allows us to select subjects with homogeneously high risk of diabetes for participation in prevention trials.

Adolescent↗
PubMed2002

Treatment of autoimmune diabetes recurrence in non-obese diabetic mice by mouse interferon-beta in combination with an analogue of 1alpha,25-dihydroxyvitamin-D3.

Autoimmune diabetes recurrence is in part responsible for islet graft destruction in type 1 diabetic individuals. The aim of the present study was to design treatment modalities able to prevent autoimmune diabetes recurrence after islet transplantation in spontaneously diabetic NOD mice. In order to avoid confusion between autoimmune diabetes recurrence and allograft rejection, we performed syngeneic islet transplantations in spontaneously diabetic NOD mice. Mice were treated with mouse interferon-beta (IFN-beta, 1 x 105 IU/day), a new 14-epi-1,25-(OH)2D3-analogue (TX 527, 5 microg/kg/day) and cyclosporin A (CsA, 7.5 mg/kg/day) as single substances and in combinations. Treatment was stopped either 20 days (IFN-beta and CsA) or 30 days (TX 527) after transplantation. Autoimmune diabetes recurred in 100% of control mice (MST 11 days). None of the mono-therapies significantly prolonged islet graft survival. Combining CsA with TX 527 maintained graft function in 67% of recipients as long as treatment was given (MST 31 days, P < 0.01 versus controls). Interestingly, 100% of the IFN-beta plus TX 527-treated mice had normal blood glucose levels during treatment, and even had a more pronounced prolongation of graft survival (MST 62 days, P < 0.005 versus controls). Cytokine mRNA analysis of the grafts 6 days after transplantation revealed a significant decrease in IL-2, IFN-gamma and IL-12 messages in both IFN-beta plus TX 527- and CsA plus TX 527-treated mice, while only in the IFN-beta with TX 527 group were higher levels of IL-10 transcripts observed. Therefore, we conclude that a combination of IFN-beta and TX 527 delays autoimmune diabetes recurrence in islet grafts in spontaneously diabetic NOD mice.

Alkynes↗
PubMed2002

A murine interleukin-4-Ig fusion protein regulates the expression of Th1- and Th2-specific cytokines in the pancreas of NOD mice.

Interleukin (IL)-4 is a key cytokine in T-helper type 2 (Th2) immune response. We have constructed a dimeric IL-4 molecule consisting of the murine IL-4 and the murine Fc part of IgG2a. We first tested the biological activity of the chimeric protein by in vitro studies using isolated murine spleen cells. IL-4-Ig was found to downregulate LPS-induced IFN-gamma and TNF-alpha production. The immunomodulatory potential of the fusion protein was also analyzed in non-obese diabetic (NOD) mice, an animal model for human type 1 diabetes. Female NOD mice aged 10 weeks were treated once with cyclophosphamide to accelerate and synchronize the progression of insulitis. Treatment with IL-4-Ig induced strong modulation of the pancreatic cytokine balance. Expression was downregulated for both Th1-specific cytokine IFN-gamma and the Th2-specific cytokine IL-10. IL-12p40 expression was only slightly affected. Interestingly, infiltration increased in the islets of IL-4-Ig-treated animals, and therefore did not correlate with the decreased IFN-gamma expression. Hence, IL-4-Ig did not prevent the progression from peri- to intra-insulitis, but suppressed inflammatory cytokine production. In most experiments, the biological activity of IL-4-Ig and IL-4 was comparable. We conclude that treatment with the chimeric protein IL-4-Ig effectively downregulates Th1 responses but simultaneously augments intra-islet infiltration.

Animals↗
PubMed2002

[1,25-dihydroxyvitamin D3: the endocrine system meets the immune system].

1,25(OH)2D3, the activated form of vitamin D, is well known for its effects on calcium and bone metabolism, but also non-classical effects on cells of the immune system were described, in vivo as well as in vitro. Structural analogues have been developed with less calcemic effects, but at least comparable immune effects. Our group showed that treatment with 1,25(OH)2D3 can protect the NOD mouse, the murine model for type 1 diabetes, from diabetes in primary, secondary and tertiary prevention. This effect is based on shifts in cytokine profiles (Thelper1 to Thelper2), that occur specifically for the autoantigens, and on enhanced sensitivity of the autoreactive T lymphocytes to apoptotic signals thus leading to a better elimination of these potentially dangerous cells. 1,25(OH)2D3 and its analogues can therefore be considered as interventions aimed at the prevention or treatment of human type 1 diabetes.

Animals↗
PubMed2002

[How patients react when glaucoma is diagnosed?].

PURPOSE: Evaluate the psychological consequences of announcing the diagnosis of glaucoma. MATERIALS AND METHODS: Two hundred patients completed a 20-item questionnaire designed to analyze the context in which glaucoma was discovered and the patients' reaction to this diagnosis. Behavioral modification in patients and their families are specified as well as their perception of the information received. COMMENTS: Most patients had open-angle glaucoma and showed either an anxious or a passive reaction to the announcement of the diagnosis. Severe anxiety led to prescription of minor tranquilizers or antidepressants in 11% of cases. Nearly half of the patients declared that they had modified their behavior after receiving the diagnosis, indicating a need to play an active role in disease management. A large majority of the patients were conscious of the risk of blindness related to glaucoma; however, they did not feel ill but rather handicapped . Most were dissatisfied with the information provided by their doctor and sought other sources of information. CONCLUSION: Announcing a diagnosis of glaucoma is a decisive step in the physician-patient relationship, known to be important in future treatment compliance. Better adapted information with regular reevaluation of the need for additional information is necessary. The psychological impact should be evaluated regularly in order to promote an active role on the part of the patient and avoid a decline in quality of life.

Aged↗