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Biomedical subjects

C Matte

Publications and source records attributed to C Matte.

At least 19 recordsLinked to original sources

Leishmania donovani-induced macrophages cyclooxygenase-2 and prostaglandin E2 synthesis.

Prostaglandin E2 (PGE2) secretion during Leishmania infection has been reported. However, the signalling mechanisms mediating this response are not well understood. Since cyclooxygenase-2 (COX-2) and cytosolic phospholipase A2 (cPLA2) are involved in PGE2 synthesis in response to various stimuli, the implication of these enzymes was evaluated in Leishmania-infected phorbol myristate acetate-differentiated U937 human monocytic cell line. Time-course experiments showed that PGE2 synthesis increased significantly in parallel with COX-2 expression when cells were incubated in the presence of Leishmania donovani promastigotes or lipopolysaccharides (LPS). Increase in cPLA2 mRNA expression was only detected when cells were stimulated with LPS. Indomethacin, genistein, and H7, which are antagonists of COX-2, protein tyrosine kinase (PTK) and protein kinase C (PKC), respectively, inhibited PGE2 production induced by L. donovani and LPS. However, only H7 inhibited COX-2 mRNA synthesis, and there was a significant correlation between PGE2 inhibition and reduced COX-2 expression. Collectively, our results indicate that infection of U937 by L. donovani leads to the generation of PGE2 in part through a PKC-dependent signalling pathway involving COX-2 expression. They further reveal that PTK-dependent events are necessary for Leishmania-induced PGE2 generation, but not for COX-2 expression. A better understanding of the mechanisms by which Leishmania can induce PGE2 production could provide insight into the pathophysiology of leishmaniasis and may help to improve therapeutic approaches.

Animals↗

Peroxovanadium-mediated protection against murine leishmaniasis: role of the modulation of nitric oxide.

The phosphotyrosine phosphatase inhibitor bpV(phen) has the ability to markedly decrease the progression of leishmaniasis in vivo. Here, we have identified the mechanisms that are responsible for this protective effect. We report that two potent peroxovanadium (pV) compounds, bpV(phen) and bpV(pic), control progression of leishmaniasis in a similar manner by modulating NO-dependent microbicidal action. We observed that their injection can rapidly and transiently induce the expression of inducible NO synthase (iNOS) in livers of mice and enhance circulating nitrate levels. Treatment of mice with bpV(phen) or bpV(pic) completely controlled progression of leishmaniasis in an NO-dependent manner, since inhibition of iNOS with aminoguanidine completely reversed this pV-mediated protection. This NO-dependent pV-mediated protection was further demonstrated by the incapacity of bpV(phen)-treated Nramp-/-, iNOS-/- mutant mice to control Leishmania major infection. Using an air pouch model, we showed that bpV(phen) can strongly modulate secretion of L. major-induced pro-inflammatory molecules and neutrophil recruitment. In addition, we observed that bpV(phen) per se can strongly induce the expression of Th1 type cytokines over Th2 in spleens of animals. Overall, this study has allowed us to establish the in vivo functional and immunological events involved in pV-mediated protective mechanism against leishmaniasis and that NO plays a pivotal role in this process.

Animals↗

HLA-G and HLA-E polymorphisms in an indigenous African population. The ZVITAMBO Study Group.

Studies of HLA-G and HLA-E polymorphisms in different populations from many industrialized countries have uniformly reported little sequence variation within these genes. To date, the polymorphism of these genes has not been characterized in populations from developing countries where more sequence variation would be anticipated due to greater exposure to microbial pathogens. In order to address this issue, we have recently investigated the polymorphism of these MHC genes in an indigenous African population (Shona ethnic group). HLA-G and HLA-E alleles were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS) analysis in 108 unrelated women recruited from maternity clinics and hospitals in Harare (Zimbabwe). The genotyping analysis identified six different HLA-G alleles and three HLA-E alleles in this population. Of interest, the null-allele HLA-G*0105N was found with 11.1% of frequency, which is higher than in other populations tested so far. We observed the presence of 15 distinct HLA-G genotypes and 6 HLA-E genotypes. These data indicate that this African population contains low levels of allelic polymorphism similar to ethnic groups from industrialized countries. This is the first report describing HLA-G and HLA-E polymorphisms in an indigenous African population.

Africa↗

Modulation of interferon-gamma-induced macrophage activation by phosphotyrosine phosphatases inhibition. Effect on murine Leishmaniasis progression.

Phagocyte functions are markedly inhibited after infection with the intracellular protozoan parasite Leishmania. This situation strongly favors the installation and propagation of this pathogen within its mammalian host. Previous findings by us and others have established that alteration of several signaling pathways (protein kinase C-, Ca2+- and protein-tyrosine kinases-dependent signaling events) were directly responsible for Leishmania-induced macrophage (MO) dysfunctions. Here we report that modulation of phosphotyrosine-dependent events with a protein tyrosine phosphatases (PTP) inhibitor, the peroxovanadium (pV) compound bpV(phen) (potassium bisperoxo(1,10-phenanthroline)oxovanadate(Vi)), can control host-pathogen interactions by different mechanisms. We observed that the inhibition of parasite PTP resulted in an arrest of proliferation and death of the latter in coincidence with cyclin-dependent kinase (CDK1) tyrosine 15 phosphorylation. Moreover the treatment of MO with bpV(phen) resulted in an increased sensitivity to interferon-gamma stimulation, which was reflected by enhanced nitric oxide (NO) production. This enhanced IFN-gamma-induced NO generation was accompanied by a marked increase of inducible nitric oxide synthase (iNOS) mRNA gene and protein expression. Finally we have verified the in vivo potency of bpV(phen) over a 6-week period of daily administration of a sub-toxic dose. The results revealed its effectiveness in controlling the progression of visceral and cutaneous leishmaniasis. Therefore PTP inhibition of Leishmania and MO by the pV compound bpV(phen) can differentially affect these eukaryotic cells. This strongly suggests that PTP plays an important role in the progression of Leishmania infection and pathogenesis. The apparent potency of pV compounds along with their relatively simple and versatile structure render them attractive pharmacological agents for the management of parasitic infections.

Animals↗

Central precocious puberty following feminizing right ovarian granulosa cell tumor.

A 7-month-old girl presented with ascites and breast enlargement due to right ovarian granulosa cell tumor. After tumor removal, the clinical signs of incomplete precocious puberty regressed. Four years later, the patient reappeared with signs of precocious puberty. Our investigations proved that this was not due to tumor recurrence, but it was a true central precocious puberty. She responded well to therapy with a luteinizing hormone releasing hormone agonist, and 3 years after onset of this therapy, she is growing at a normal prepubertal rate.

Antineoplastic Agents, Hormonal↗

Structure and development of the egg of the glossiphoniid leech Theromyzon rude: reorganization of the fertilized egg during completion of the first meiotic division.

Reorganization of the fertilized egg during completion of the first meiotic division was studied in the glossiphoniid leech Theromyzon rude. Rotation of the meiotic spindle, presumably as a result of changes in the length and arrangement of astral fibers, allows one of its poles to approach the prospective animal pole (AP), which appears as a differentiated region of the ectoplasm. The peripheral spindle pole is greatly modified during its anchorage to the AP and is dismantled upon emission of the first pole cell. Meanwhile, the central spindle pole is less modified and is reused during the second meiotic division. Redistribution of microvilli, as well as rearrangement of the ectoplasmic actin lattice, lead to remodeling of the egg surface. Emission of the first pole cell is preceded by a contraction wave that seems to arise by condensation of subcortical actin filaments at the equator of the egg. Poleward displacement of this wave causes evagination of the AP and ooplasmic segregation. A cytokinetic contractile ring forms by assembly of cortical actin filaments at the base of the AP evagination. When this process is disturbed by colchicine or cytochalasin B treatment, abortive or ghost pole cells may be formed.

Animals↗

[Crohn's disease limited to the appendix. Apropos of a case].

A rare case of Crohn's disease limited to the appendix is reported in an 18 years old adolescent, hospitalised as having acute appendicitis. Appendectomy was performed. There were no postoperative complication and no recurrence after 3 years follow-up. Surgical indications are discussed and literature reviewed.

Abscess↗

Development of mouse embryos following the destruction of blastomeres.

Preimplantation mouse embryos in different stages of development were cultured in vitro following the puncture of one or more blastomeres through the zona pellucida. The percentage of embryos that developed to the blastocyst stage was lower when puncturing was done in later stages than in earlier stages, thus showing that regulation capability diminishes as development proceeds. Cell debris of punctured blastomeres were always found under the zona pellucida, in any sector of the blastocyst, and did not prevent the sealing between the underlying cells. The plasma membrane of the punctured blastomeres vacuolized and disappeared within minutes of the operation. The space left by punctured external blastomeres of 16-cell morulae was filled by neighbour peripheral cells and not by inner cells, suggesting cell differentiation prior to blastocoel formation.

Animals↗

[Quantitative measurement of red cell antigens with Groupamatic].

Groupamatic 360 can be adapted to the quantitative measurement of erythrocyte agglutination reactions. Here the authors give the necessary conditions to obtain the best sensitivity and the best reproductibility. They have considered globular suspensions, incubation of the erythrocyte antiserums mixtures, centrifugation, agitation, photometric measurement. As concerns the quantitative technique, we used the average peripheral measurement obtained in the twleve cuvettes of the same selected disc sector. The calibration is fixed to 50 mV for a non agglutinated red cell suspension and to 950 mV for albumin in a saline solution. In these conditions, the best discrimination is obtained for agglutination with measures between 400 and 800 mV. The maximum sensitivity is reached with reactions corresponding to 600 mV, that is to say in our selected conditions with 50% of free red cells. The choice of the zone between 500 and 600 mV enables to detect variations from 1.5 to 2% in an antibody solution concentration. This zone is particularly favorable for quantitative work. Although a part of these operations in this preliminary work were manually effected, the automatic centrifugation, agitation, photometric measurement and results print out make possible a large number of measurements with very satisfactory reproductibility conditions. Besides, these experiments pointed out some factors of improvement which will be helpful for the new 360 G Groupmatic equipments.

ABO Blood-Group System↗

Automation of a flocculation test for syphilis on Groupamatic equipment.

A flocculation reaction employing a cardiolipid antigen was used for syphilis screening on Groupamatic equipment in parallel with conventional screening reactions: Kolmer CF, RPCF, Kahn, Kline, and RPR. The positive samples were confirmed by FTA-200, FTA-ABS, TPI, and in some cases by TPHA. There were 5,212 known samples which had already been tested by all methods and of which 1,648 were positive, and 58,636 screened samples including 65 positives. Half of the samples in the first series were taken without anticoagulant; the remainder were collected in potassium EDTA. The percentage of false positives with the Groupamatic was about 1-4 per cent. The percentage of false negatives among positve (greater than or equal+) samples varied from 0-18 to 1-3 per cent.; on the other hand the sensitivity was less good for samples giving doubtful and/or dissociated reactions in conventional screening reactions. The specificity and sensitivity of this technique are acceptable for a blood transfusion centre. The reproducibility is excellent and the automatic reading of results accurate. Additional advantages are rapidity (340 samples processed per hour); simultaneous performance of eleven other immunohaematological reactions; no contamination between samples; automatic reading, interpretation, and print-out of results; and saving of time because samples are not filed sequentially and are automatically identified when the results are obtained. Although the importance of syphilis in blood transfusion seems small, estimates of the risk are difficult and further investigations are planned.

Autoanalysis↗