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Biomedical subjects

C Mathieu

Publications and source records attributed to C Mathieu.

At least 91 records · Page 5Linked to original sources
PubMed1999

The mean of sperm parameters in semen donations from the same donor. An important prognostic factor in insemination.

We analysed 12,100 consecutive cycles of artificial insemination by donor spermatozoa in 1901 infertile couples. In our analysis, particular attention was given to finding an appropriate way of taking into account the respective effects of female and male factors on the pregnancy success rate and the level at which these factors act (cycle vs. woman and donation vs. donor). A total of 1213 pregnancies occurred. The pregnancy rate per cycle was lower as the age of the woman increased (p < 0.0001) and varied with the type of infertility: fecundity was higher (p = 0.03) in the case of azoospermia than of severe oligozoospermia. After taking into account these factors, significant unexplained variation in likelihood to conceive remained. A part of this heterogeneity was shown to be due to variation in fecundability between semen donors. In order to explain this heterogeneity between donors, compositional covariates were used, particularly the mean of results of the semen analysis performed for donations from the same donor. For each semen characteristic, the overall mean of the different donations of a donor was an important predictive factor of successful insemination: after taking into account all of the other factors, the odds ratios for an increase of 50 x 10(6)/mL spermatozoa, of a 20% increase in sperm motility and of a 2 point increase in the post-thaw quality index, were, respectively, 1.13, 1.37 and 1.56. After adjustment for these factors, the specific characteristics of each semen donation were no longer significantly predictive of successful insemination. This observation has a biological interpretation: sperm with low parameters but produced by a normally fertile man can have a satisfactory success rate.

Adult↗
PubMed1999

Characterisation of a cDNA encoding gamma-glutamylcysteine synthetase in Medicago truncatula.

A gamma-ECS cDNA from Medicago truncatula was isolated using an Arabidopsis thaliana cDNA as probe. The analysis of the amino acid sequence deduced from this cDNA revealed 80% identity with the gamma-ECS from A. thaliana and Brassica juncea and suggested a plastidial localisation for the enzyme. Gamma-ECS activity and high level of GSH were detected in the gamma-ECS-deficient E. coli strain expressing a fusion protein containing the M. truncatula gamma-ECS protein. Southern blot analysis suggests that gamma-ECS is encoded by a small multigenic family in M. truncatula and shows that homologous genes are present in two other leguminous plants, Medicago sativa and Pisum sativum. Gamma-ECS gene expression was analysed by Northern blot in seedlings, plantlets and mature plants.

Arabidopsis↗
PubMed1999

[Results of oocyte donation in France (Study Group on Oocyte Donation)].

The French study group on oocyte donation, named GEDO, reports the results concerning the oocyte donation activity in France during 1998, including information from all the centers in effective operation except one. These data describe the recipients' and donors' situation and give the analysis of the results obtained.

Female↗
PubMed1999

The role of interferon regulatory factor-1 in cytokine-induced mRNA expression and cell death in murine pancreatic beta-cells.

Combinations of cytokines, including interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma), induce nitric oxide (NO) production and cell death in pancreatic islet cells. We have previously shown that these events are preceded by increased expression of the transcription factor interferon regulatory factor-1 (IRF-1). We utilized an IRF-1 knockout mouse (IRF-1-/-) to investigate the role of IRF-1 in cytokine-induced islet- and beta-cell gene expression and cell death. For this purpose, pancreatic islets or FACS-purified beta-cells were isolated from wild type (wt) or IRF-1-/- mice. These cells were exposed for different time points to IL-1beta (50 U/mI), IFN-gamma (1,000 U/ml) and/or TNF-alpha (1,000 U/ml) before being harvested for determination of viability (by nuclear dyes) and mRNA expression (by RT-PCR with specific primers). Following a 24 hours exposure to IL-1beta or IL-1beta + IFN-gamma, pancreatic islets isolated from IRF-1-/- mice presented a 30-50% reduction in medium nitrite accumulation and inducible NO-synthase (iNOS) expression. Interestingly, both wt and IRF-1-/- purified beta-cells failed to produce NO in response to IL-1beta alone, but presented a similar increase in nitrite accumulation and iNOS expression following exposure to IL-1beta + IFN-gamma. The basal expression of MHC class I mRNA was lower in IRF-1-/- islet cells (30% reduction), but there was a similar 2-4 fold-increase in MHC expression in islet cells from both strains following cytokine exposure. IL-1beta induced serine protease inhibitor-3 (SPI-3; a putative cellular "defense" protein) mRNA expression in both wt and IRF-1-/- islets or beta-cells. IFN-gamma decreased the IL-1beta-induced SPI-3 expression in wt islets or beta-cells, but induced a 5-fold increase in the expression of this mRNA in IRF-1-/- islets cells, suggesting that IRF-1 mediates an inhibitory effect of IFN-gamma on SPI-3 expression. Treatment of whole islets for 3 days with IL-1beta + IFN-gamma induced significantly more islet cell death in wt than in IRF-1-/- mice (respectively 85 +/- 3% versus 31 +/- 4% dead cells). On the other hand, prolonged exposure (3-9 days) of FACS-purified beta-cells to the same cytokines, or a combination of 3 cytokines, led to a similar increase in cell death in both IRF-1-/- and wt islets. In conclusion, IRF-1 contributes to cytokine-induced islet iNOS expression and cell death. These effects are absent in purified beta-cells, suggesting that IRF-1 may mediate its effects on whole islets via activation of non-endocrine cells (e.g. macrophages and ductal cells) present in these preparations.

Animals↗
PubMed1998

Prevention of autoimmune destruction of syngeneic islet grafts in spontaneously diabetic nonobese diabetic mice by a combination of a vitamin D3 analog and cyclosporine.

BACKGROUND: Type 1 diabetes is characterized by the presence of an autoimmune memory, responsible for the destruction of even syngeneic islet grafts. This recurrence of autoimmunity is partly responsible for the need of extensive immunosuppression in pancreas and islet transplantation in type 1 diabetic patients. The aim of the study was to evaluate the capacity of a 20-epi-analog of vitamin D3, KH1060, both alone and in combination with cyclosporine (CsA) to prevent diabetes recurrence in syngeneic islet grafts in nonobese diabetic (NOD) mice. METHODS: Spontaneously diabetic NOD mice grafted with syngeneic islets (n=500) under the kidney capsule were treated with KH1060, CsA, or a combination of both drugs from the day before transplantation until recurrence or 60 days after transplantation. RESULTS: Vehicle-treated mice showed a recurrence of diabetes in 100% of cases (n=17) within 4 weeks. Treatment with high doses of CsA (15 mg/kg/day) or KH1060 (1 microg/kg/2 days) significantly prolonged islet survival (60 days and 50 days, respectively, versus 9.5 days in controls; P<0.001 and P<0.0001). Mice treated with subtherapeutical doses of both drugs combined (KH1060 0.5 microg/kg/2 days + CsA 7.5 mg/kg/day) had significant prolongation of graft survival (48 days; P<0.001) and more importantly, four of five mice that were still normoglycemic 60 days after transplantation showed no recurrence after discontinuation of all treatment. Histology of the grafts of control and combination-treated mice demonstrated that graft infiltration and islet destruction were less severe in grafts of combination-treated mice. Cytokine mRNA analysis in the grafts 6 days after transplantation revealed a clear suppression of interleukin-12 and T helper 1 cytokines and higher levels of interleukin-4 in combination-treated mice. CONCLUSIONS: KH1060, an analog of 1,25(OH)2D3, delays autoimmune disease recurrence after syngeneic islet transplantation in NOD mice, both alone and especially in combination with CsA, possibly restoring tolerance to beta cells in 30% of cases.

Animals↗
PubMed1998

Drug resistant tuberculosis in prisons in Azerbaijan: case study.

OBJECTIVES: To document the existence of drug resistance in a tuberculosis treatment programme that adheres strictly to the DOTS principles (directly observed treatment, short course) and to determine the extent of drug resistance in a prison setting in one of the republics of the former Soviet Union. DESIGN: Case study. SETTING: Central Penitentiary Hospital in Baku, the referral centre for tuberculosis patients from all prisons in Azerbaijan. SUBJECTS: Prisoners with tuberculosis: 28 selected patients not responding clinically or bacteriologically to the standard treatment (group 1) and 38 consecutive patients at admission to the programme (group 2). MAIN OUTCOME MEASURES: Drug resistance of Mycobacterium tuberculosis strains grown from sputum. RESULTS: All the non-responding patients (group 1) had strains resistant to at least one drug. 25 (89%) of the non-responding patients and nine (24%) of the consecutive patients had M tuberculosis strains resistant to both rifampicin and isoniazid. A further 17 patients in group 2 had strains resistant to one or more first line drugs. CONCLUSIONS: Drug resistant M tuberculosis strains are common in prisons in Azerbaijan. Tuberculosis problems tend to be worse in prisons, but prisoners and former prisoners may have an important role in the transmission of tuberculosis, particularly of drug resistant forms, in the community. National programmes to control tuberculosis will have to take into account and address the problems in prisons to ensure their success.

Antibiotics, Antitubercular↗
PubMed1998

Diabetes mellitus and female sexuality: a review of 25 years' research.

Diabetes mellitus may cause debilitating somatic complications and a high psychosocial burden. Impaired sexual function (erectile dysfunction) is a well-established complication in men. Does diabetes also have an effect on sexuality of women? Since the first publication in 1971, only 15 studies in this area have been published and their results are contradictory. The purpose of this article is to offer a review of these results. As a conclusion, a new hypothesis on the specific influence of diabetes on female sexuality and suggestions for further research are formulated.

Adolescent↗
PubMed1998

Direct detection of radicals in intact soybean nodules: presence of nitric oxide-leghemoglobin complexes.

Electron paramagnetic resonance spectroscopy has been employed to examine the nature of the metal ions and radicals present in intact root nodules of soybean plants grown in the absence of nitrate. The spectra obtained from nodules of different ages using this non-invasive technique show dramatic differences, suggesting that there are both qualitative and quantitative changes in the metal ion and radical species present. A major component of the spectra obtained from young nodules is assigned to a complex (Lb-NO) of nitric oxide (NO.) with the heme protein leghemoglobin (Lb). This Lb-NO species, which has not been previously detected in intact root nodules of plants grown in the absence of nitrate, is thought to be formed by reaction of nitric oxide with iron(II) leghemoglobin. The nitric oxide may be generated from arginine via a nitric oxide synthase-like activity present in the nodules of the soybean plants, in a manner analogous to that recently described for Lupinus albus. This Lb-NO complex is present at lower concentrations in older nodules, and is almost completely absent from senescent nodules. Exposure of young and mature nodules to oxidant stress, in the form of hydrogen peroxide, results in changes in the EPR spectra, with the loss of the signals from the Lb-NO complex and appearance of absorptions similar to those from untreated senescent nodules. These results suggest that there are characteristic changes in both the metal ion complexes and radicals present in intact root nodules of different ages, and support the theory that nitric oxide and other radicals play a significant role in determining the nitrogen fixing activity of root nodules; the modulatory activity of NO. may involve regulation of gene activity.

Electron Spin Resonance Spectroscopy↗
PubMed1998

Tissue-specific expression of genes encoding isoforms of the mitochondrial ATPase beta subunit in Nicotiana sylvestris.

We report here that the catalytic beta subunit of the mitochondrial ATPase/ATP synthase is encoded by a small multigenic family in the diploid tobacco Nicotiana sylvestris (nsatp2 genes). cDNAs and genes corresponding to the beta1, beta2 and beta3 (pollen specific) isoforms previously detected by 2D-SDS PAGE were isolated. Nsatp2.1 and nsatp2.2 transcripts were found in all vegetative and reproductive tissues analysed. In contrast, nsatp2.3 transcripts were found exclusively in bicellular pollen. As a whole, steady-state transcript levels of nuclear nsatp2 and mitochondrial atp1 genes were found to be closely correlated.

Amino Acid Sequence↗
PubMed1998

1,25-Dihydroxyvitamin D3 restores sensitivity to cyclophosphamide-induced apoptosis in non-obese diabetic (NOD) mice and protects against diabetes.

The activated form of vitamin D, 1,25(OH)2D3, and its analogues can prevent type I diabetes in NOD mice. Protection is achieved without signs of systemic immunosuppression and is associated with a restoration of the defective immune regulator system of the NOD mice. The aim of the present study was to investigate whether this restoration of regulator cell function is the only mechanism in the prevention of diabetes by 1,25(OH)2D3. We tested therefore if 1,25(OH)2D3 could prevent cyclophosphamide-induced diabetes, since diabetes occurring after cyclophosphamide injection is believed to be due to an elimination of suppresser cells. NOD mice treated with 1,25(OH)2D3 (5 microg/kg every 2 days) from the time of weaning were clearly protected against diabetes induced by cyclophosphamide (200 mg/kg body wt at 70 days old) (2/12 (17%) versus 36/53 (68%) in control mice, P < 0.005). By co-transfer experiments it was demonstrated that cyclophosphamide had indeed eliminated the suppresser cells present in 1,25(OH)2D3-treated mice. Since cyclophosphamide injection did not break the protection offered by 1,25(OH)2D3, it was clear that diabetogenic effector cells were affected by 1,25(OH)2D3 treatment as well. This was confirmed by the finding that splenocytes from 1,25(OH)2D3-treated mice were less capable of transferring diabetes in young, irradiated NOD mice, and by the demonstration of lower Th1 cytokine levels in the pancreases of 1,25(OH)2D3-treated, cyclophosphamide-injected mice. This better elimination of effector cells in 1,25(OH)2D3-treated mice could be explained by a restoration of the sensitivity to cyclophosphamide-induced apoptosis in both thymocytes and splenocytes, in normally apoptosis-resistant NOD mice. Altogether, these data indicate that the protection against diabetes offered by 1,25(OH)2D3 may be independent of the presence of suppresser cells, and may involve increased apoptosis of Th1 autoimmune effector cells.

Animals↗
PubMed1998

Recent developments in the use of vitamin D analogues.

The activated form of vitamin D3, 1 alpha,25(OH)2D3, not only plays a central role in bone and calcium metabolism, but also has potent antiproliferative and prodifferentiating effects. Moreover, the combined presence of 25(OH)D3-1 alpha-hydroxylase, as well as the vitamin D receptor in several tissues introduced the idea of a paracrine role for 1 alpha,25(OH)2D3. By introducing chemical modifications into the flexible molecule 1 alpha,25(OH)2D3, a whole generation of vitamin D analogues was created. Due to a clear dissociation of the antiproliferative and prodifferentiating effects from calcaemic effects, these analogues can be used not only for the treatment of bone disorders but also for non-classical applications. In the present review, a summary is given on the use of the 1 alpha,25(OH)2D3 analogues for the treatment of psoriasis, cancer and immune disorders together with new insights in the mechanism of action of these analogues.

Animals↗
PubMed1998

Prevention of type I diabetes in nonobese diabetic mice by late intervention with nonhypercalcemic analogs of 1,25-dihydroxyvitamin D3 in combination with a short induction course of cyclosporin A.

In nonobese diabetic (NOD) mice, type I diabetes can be prevented without generalized immunosuppression by nonhypercalcemic analogs of vitamin D3 when treatment is started early, i.e. before the autoimmune attack, reflected by insulitis, occurs. The aim of this study was to investigate whether these substances can arrest progression to clinically overt diabetes when administered in a more advanced disease stage, namely when the autoimmune attack is ongoing, reflecting the situation in prediabetic subjects in whom immune intervention is being considered. We, therefore, evaluated the protective potential of MC1288 (20-epi-1,25-dihydroxyvitamin D3) a nonhypercalcemic analog of 1,25-dihydroxyvitamin D3, both alone and in combination with a short induction course of cyclosporin A, in NOD mice that already have insulitis, as demonstrated in pancreatic biopsies performed 15 days before the start oftherapy. Subsequently, mice were randomized into a control group, receiving the treatment vehicle (n = 26), and three treatment groups, receiving, respectively, 7.5 mg/kg x day cyclosporin A (CyA) from days 85-105 (n = 19), 0.1 microg/kg x 2 days MC1288 from days 85-200 (n = 20), or the combination of these two regimens (n = 20). At the time of the pancreatic biopsy (day 70), insulitis was evenly distributed in all groups, and 27.7% of the islets scored showed signs of destructive insulitis. Diabetes outcome by 200 days was 74% (14 of 19) in the CyA-treated group, comparable to the diabetes incidence in control mice (65%; 17 of 26; P = NS). Treatment with MC1288 alone could not reduce disease incidence (70%; 14 of 20), but the combination therapy reduced diabetes incidence to 35% (7 of 20; P < 0.05 vs. untreated; P < 0.01 vs. CyA group; P < 0.025 vs. MC1288). All treatments were well tolerated, without major side-effects on calcium or bone metabolism and without signs of generalized immunosuppression. Cotransfer experiments could not reveal the induction of suppressor cells. Reverse transcription-PCR on pancreatic tissue revealed significantly lower levels of interferon-gamma and higher levels of interleukin-4 in the combination group. In conclusion, nonhypercalcemic analogs of 1,25-dihydroxyvitamin D3 administered to NOD mice when the autoimmune disease is already active can prevent clinical diabetes when this therapy is combined with a short induction course of an immunosuppressant such as CyA.

Animals↗
PubMed1998

Sex difference in resistance to dexamethasone-induced apoptosis in NOD mice: treatment with 1,25(OH)2D3 restores defect.

The NOD mouse, a model for type 1 diabetes, is characterized by resistance to apoptosis in immunocytes. The aim of this study was to investigate a link between apoptosis in NOD thymocytes and autoimmunity. First, we demonstrated that the sexual dimorphism in diabetes incidence in NOD mice (females are more diabetes-prone than males) is reflected by differences in apoptosis. Apoptosis in NOD thymocytes, 24 h after dexamethasone, was decreased in both sexes compared with C57B1/6, but it was lower in female mice (26 +/- 2%) than in male mice (50 +/- 3%, P < 0.001). Further, we demonstrated that sex hormones themselves play a central role in this difference, since castration of NOD male mice, which increases diabetes incidence, decreased apoptosis levels (32 +/- 2%), while treatment of NOD female mice with dihydrotestosterone, which protects against diabetes, restored apoptosis to male levels (42 +/- 1.5%). Finally, we demonstrated that 1,25-dihydroxyvitamin D3, a steroid hormone that prevents diabetes in NOD mice, restored apoptosis levels to C57B1/6 reference levels. This improved apoptosis was seen in male (68 +/- 1 vs. 50 +/- 3% in untreated NOD mice, P < 0.001) but especially in female NOD mice (51 +/- 5 vs. 26 +/- 2% in untreated NOD mice, P < 0.001). Fluorescence-activated cell sorter analysis of thymocyte subsets revealed marked differences, especially in CD4+CD8+ and CD4+ cells. We conclude that the sexual dimorphism in diabetes incidence in NOD mice is paralleled by a dimorphism in resistance to apoptotic signals in NOD thymocytes. This resistance to apoptosis is driven by sex hormones and is corrected by 1,25-dihydroxyvitamin D3.

Animals↗
PubMed1997

Protection against autoimmune diabetes in mixed bone marrow chimeras: mechanisms involved.

After bone marrow transplantation, complete nonobese diabetic (NOD) into (NOD x C57Bl/10)F1 chimeras developed insulitis in 100% (7/7) and diabetes in 58% (7/12) of cases. In contrast, when mixed chimerism was induced, a near complete protection against insulitis (3/23, p < 0.0001 vs complete chimeras) and diabetes (0/25, p < 0.001 vs complete chimeras) was achieved even in chimeras with as few as 5% F1 cells. In cotransfer experiments, splenocytes from mixed chimeras failed to prevent diabetes, thus overruling a role for suppressor cells in protection. Whereas splenocytes from complete chimeras transferred diabetes into young irradiated NOD mice in all cases, NOD splenocytes from mixed chimeras only rarely transferred diabetes (3/16, p < 0.01 vs complete chimeras), suggesting that the latter cells had developed tolerance toward beta cells. To achieve this tolerance, the presence of an F1 thymus was not needed. Indeed, whereas splenocytes isolated from complete chimeras were diabetogenic when transferred into neonatally thymectomized irradiated NOD recipients (3/4), they failed to induce diabetes when transferred into neonatally thymectomized irradiated F1 recipients in case again a state of mixed chimerism was induced (0/4, p < 0.001 vs NOD recipients). Finally, a role for non-MHC Ags was demonstrated by experiments in F1 mice crossed between NOD and C57Bl/6, a strain congenic to C57Bl/10. Here protection against disease was only seen in the presence of high levels of F1 cells (>25%). In conclusion, mixed bone marrow chimerism can induce self-tolerance in autoimmunity prone NOD immune cells. This can be achieved extrathymically but may depend on non-MHC Ags and the level of chimerism.

Adoptive Transfer↗