PubMed Health⌕ Search

Biomedical subjects

M Duval

Publications and source records attributed to M Duval.

At least 19 recordsLinked to original sources
PubMed2001

Human cytomegalovirus infection of bone marrow myofibroblasts enhances myeloid progenitor adhesion and elicits viral transmission.

Human cytomegalovirus (CMV) infection of bone marrow transplant recipients can cause pancytopenia, as well as life-threatening interstitial pneumonia. CMV replicates actively in bone marrow stromal cells, whereas it remains latent in hematopoietic progenitors. Our aim was to study the influence of CMV infection on adherence of CD34(+) cells to the myofibroblastic component of human bone marrow and examine transmission of virus from myofibroblasts to CD34(+) cells. We show that smooth actin, but not fibronectin, organization is markedly modified by CMV infection of bone marrow stromal myofibroblasts. Nonetheless, CMV infection led to increased adherence of the CD34(+) progenitor cell line, KG1a, relative to adherence to uninfected myofibroblasts from the same donors. Adherence of CD34(+) cells to infected bone marrow myofibroblasts resulted in transfer of virions and viral proteins through close cell-to-cell contacts. This phenomenon may play a role in the pathophysiology of CMV bone marrow infection and in eventual virus dissemination.

Actins↗
PubMed2001

Characterization of the B*5002-Cw*0602-DRB1*0406-DQB1*0402 Haplotype: impact on the unrelated-bone marrow donor search strategy.

Improvements in HLA-typing by DNA-based methods now allow accurate genotyping of unrelated bone marrow (UBM) donors and recipients and also definition of haplotypes. In this regard, B*5002 has been predicted in linkage disequilibrium with Cw*0602, DRB1*0406 and DQB1*0402 based on the frequency of allele coexistence. Here, we confirm this assumption by HLA genotyping of four informative families and three unrelated individuals. In the four families, the extended haplotype HLA-B*5002, -Cw*0602, -DRB1*0406, DQB1*0402 can be definitely assigned by the mode of heritance. Furthermore, this association of alleles was also found in the three B*5002 unrelated individuals. Knowledge of the frequent linkage disequilibrium of these rare alleles can improve UBM donor search strategies.

Bone Marrow Transplantation↗
PubMed2001

Early diagnosis of adenovirus infection and treatment with cidofovir after bone marrow transplantation in children.

Adenovirus infection remains an important cause of mortality after bone marrow transplantation (BMT). Currently no efficient antiviral treatment is known. Thus, testing new modalities of early diagnosis and treatment is a crucial objective. Adenovirus infection is defined by the combination of symptoms and the isolation of virus from the source of clinical symptoms. The involvement of two or more organs and the presence of virus in blood cultures define disseminated disease. Seven children with a median age of 7 years received bone marrow transplantation for leukemia. All received an unrelated graft without T cell depletion. Adenovirus was sought in blood, urine and biopsy specimens using PCR and culture. Analysis of biopsy specimens included systematic immunohistochemistry. Cidofovir treatment was initiated as soon as biopsy revealed the histopathological signs of adenovirus. Cidofovir was given at 5 mg/kg once weekly for 3 weeks then every 2 weeks. Six patients had diarrhoea and one patient had cystitis. Adenovirus infection and disseminated disease were diagnosed in four cases and three cases, respectively. In six cases, serotype A31 was isolated from gastrointestinal biopsy and in two cases serotypes B2 and C6 were detected in blood and urine. Cidofovir treatment was associated with clinical improvement of diarrhoea, cystitis and fever in five patients, in whom the virus became undetectable in cultures and PCR analyses despite the persistence of immunodeficiency. The median follow-up was 360 days after BMT (240-570). One child died of invasive aspergillosis and another of disseminated adenovirus after interruption of cidofovir therapy. Further studies in immunocompromised patients will be needed to extend these promising results concerning the role of cidofovir in adenovirus infection.

Adenovirus Infections, Human↗
PubMed2001

Possible implication of thiopurine S-methyltransferase in occurrence of infectious episodes during maintenance therapy for childhood lymphoblastic leukemia with mercaptopurine.

6-Mercaptopurine (6-MP) is metabolized by thiopurine S-methyltransferase (TPMT), an enzyme subject to genetic polymorphism. We investigated the relationships between the TPMT locus (TPMT activity and genotype) and the pharmacological response to 6-MP during maintenance therapy of 78 children with acute lymphoblastic leukemia (ALL). For each patient, 6-MP dosage, leukocyte counts and occurrence of infectious episodes were monitored on an 8 week basis. Higher 6-MP dosage was associated with higher TPMT activity (P = 0.03) and higher average leukocyte counts (P < 0.01). Eight patients (10%) carrying a TPMT mutant genotype (one homozygous and seven heterozygous) received lower 6-MP doses (average: 48 vs 65 mg/m2/day; P = 0.02) and had on average lower leukocyte counts (2834 vs 3398 cells/mm3; P = 0.003) than patients carrying the wild-type TPMT genotype. Higher occurrence of infectious episodes graded 2 or 3 was correlated with higher 6-MP dosage (P < 0.01) but no difference was observed between TPMT mutants and TPMT wild-type patients. Patients who received 6-MP dosage above the group median (62 mg/m2/day) or having a TPMT activity above the group median (21.5 nmol/h/ml) had a higher percentage of 8 week periods with infectious episodes requiring treatment (34% vs 17% and 33% vs 19%, respectively) than those with 6-MP dose or TPMT activity below the group median (P < 0.01). In the last 25 patients enrolled in the study, steady-state erythrocyte thioguanine nucleotide (TGN) concentrations were associated with lower leukocyte counts (P= 0.01) but not with a higher occurrence of infectious episodes. In contrast, higher steady-state erythrocyte methylmercaptopurine nucleotide (MeMPN) concentrations were associated with higher 6-MP dosage (P< 0.01) and higher occurrence of infectious episodes (P < 0.001). In conclusion, during maintenance therapy of ALL, children with higher TPMT activity receive a higher 6-MP dosage and may have infectious episodes caused by metabolism of 6-MP into methylmercaptopurine nucleotides.

Adolescent↗
PubMed2000

A Light Scattering Study of the Association of Hydrophobically alpha- and alpha,omega-End-capped Poly(ethylene oxide) in Water.

Several hydrophobically alpha- and alpha,omega-end-capped poly(ethylene oxide) polymers were studied by light scattering below and above their critical association concentration, in order to understand their association mechanisms. In the case of monofunctionalized PEO, a one-step closed association model well fits the experimental data, with a limit number of aggregation of about 30, consistent with other experimental data and a theoretical approach. In the case of difunctionalized PEO, a good description of the experimental data is obtained by assuming a two-step association process: at low concentration, the formation of "flower-like" micelles is well described by a closed association model, whereas at higher concentration, the progressive bridging of these "flowers" can be modeled by an open association. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Novel inhibitors of nucleoside triphosphate diphosphohydrolases: chemical synthesis and biochemical and pharmacological characterizations.

To elucidate the physiological role played by nucleoside triphosphate diphosphohydrolase (NTPDase; EC 3.6.1.5), adenine nucleotide analogues, modified on the purine ring, have been synthesized and tested as potential inhibitors. Resistance of ATP analogues to hydrolysis and their potency as NTPDase inhibitors were evaluated. For this purpose, a particulate fraction isolated from bovine spleen was used as the enzyme source. Among the synthesized analogues, 8-thiobutyladenosine 5'-triphosphate (8-BuS-ATP) was found to be the most effective nonhydrolyzable competitive inhibitor, with an estimated K(i) of 10 microM. This nonhydrolyzable analogue did not exert any P2X-receptor-mediated effect on endothelium-denuded blood vessels, from the guinea pig mesenteric bed. In agreement with this observation, infusion of the analogue did not cause any significant blood pressure variations of the precontracted vessel. Because in previous studies on isolated turkey erythrocytes and rat astrocytes 8-BuS-ATP was not able to trigger any P2Y(1)-receptor-mediated effect, it therefore appears that this NTPDase inhibitor does not interfere with purinergic receptors.

Adenosine Triphosphate↗
PubMed2000

Reply

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

[Patient-controlled analgesia for prolonged pain in the child. An open-label feasibility study of a standardized method].

BACKGROUND: Patient-controlled analgesia (PCA) has been shown to be superior to a continuous morphine infusion for the treatment of ongoing pain in children over five years of age. Nevertheless, prescription parameters such as the bolus dosage and the possible association of a continuous background infusion have not yet been standardized. PATIENTS AND METHODS: Thirty-three children, aged four to 17, hospitalized in a pediatric hematology ward, benefited from PCA with a standardized prescription: a bolus dosage of at least 25 mg/kg, without a background infusion. Morphine consumption, side effects and efficacy on pain relief were followed. RESULTS: Median of mean morphine consumption was 0.32 mg.kg-1.d-1. Median of maximal consumption was 0.58 mg.kg-1.d-1. Mean duration was nine days. No important side effects were noted, except in two patients. They presented prolonged constipation and a poor quality of nocturnal sleep, but they also had a major depressive syndrome persisting after resolution of pain. Efficacy was comparable to a continuous intravenous infusion, and nocturnal sleep was of good quality for 31 children. CONCLUSION: This standardized technique of PCA can be used extensively in children over five years of age. It can be used as a reference for further studies.

Adolescent↗
PubMed2000

Direct micro-radioimmunoassay of the new renin inhibitor CGP 60536.

A solid phase method for direct radioimmunoassay in plasma of the new renin inhibitor CGP 60536 has been developed which does not require the extraction of the parent drug with organic solvents. The assay showed a good reproducibility down to plasma concentrations of 0.15 ng/ml (LOQ) with intra- and inter-assay coefficients of variation < or = 20%. The procedure, which requires only small volumes of plasma (25 microl), is simple to use and well suited for routine analysis. The method allows the investigation of the pharmacokinetics of CGP 60536 in animals and man given low oral doses of the drug.

Administration, Oral↗
PubMed2000

Nitric oxide relaxes the vascular smooth muscle independently of endothelin-1- and U46619-induced intracellular increase of calcium.

A balance between circulating and locally released vasoconstrictors, such as endothelin-1 (ET-1), and vasodilators, such as nitric oxide, controls vascular smooth muscle tone. In the study reported here, using the technique of simultaneous measurements of intracellular free calcium ([Ca2+]i) and tension, we investigated the effects of a nitric oxide donor, sodium nitroprusside (NaNP) on endothelin-1- and U46619- [a thromboxane angiotensin-II (TXA-II) mimetic] induced sustained increases in tension and [Ca2+]i in intact and endothelium-denuded rabbit thoracic aortas. Our results showed that, in both intact and endothelium-denuded preparations, the nitric oxide donor NaNP (10(-6) M) reverses the ET-1- (10(-7) M) and U46619- (10(-7) M) induced sustained increase in tension but not in [Ca2+]i. However, it did not reduce the ET-1- and U46619-induced responses. Our data suggest that nitric oxide production modulates vascular smooth muscle tension via a mechanism that is independent of that generated by vasoconstrictors such as ET-1 and TXA-II.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Endothelin-1 induces an endothelin-A-receptor-dependent and L-NAME-sensitive vasoconstriction in the isolated perfused guinea-pig kidney.

We have previously reported a significant contribution of ET(A)- and ET(B)-receptors in the eicosanoid-releasing properties of endothelin-1 (ET-1) in the guinea-pig perfused lung. More recently, it was found that intravenously administered ET-1 in the guinea-pig triggers the release of hypotensive and bronchoconstrictive eicosanoids which is strongly modulated by endogenous nitric oxide. In this study we investigate the contribution of both ET receptors as well as of the eicosanoids and nitric oxide to the vasoconstrictor properties of ET-1 in the guinea-pig kidney. The kidney was isolated from stunned and spinal cord-sectioned guinea-pig (300-350 g) and rapidly suspended and perfused (3 ml/min) with oxygenated Krebs solution at 37 degrees C. ET-1 (1-1000 pmol) induced dose-dependent increases in perfusion pressure in the perfused guinea-pig kidney. Furthermore, the pressor effect of a dose of ET-1 (40 pmol) was markedly reduced after a 15-min infusion of the ET(A) antagonist, BQ-123 (1 microM). The ET-1-induced vasoconstriction was restored 50 min after the cessation of BQ-123 infusion. In contrast, the selective ET(B)-receptor agonist, IRL-1620 (1-1000 pmol) was found to be inactive. Indomethacin (5 microM) and the ET(B)-receptor antagonist, BQ-788 (10 nM) did not affect the constrictor effect of ET-1. The infusion of ET-1 (0.5 and 1 microM, 5 min) in the guinea-pig kidney did not induce the release of prostacyclin or thromboxane. Finally, a 60 min infusion with the nitric oxide synthase inhibitor, L-NAME (200 microM) markedly potentiated the constrictor effects of ET-1. Our results suggest that unlike the pulmonary vasculature, the guinea-pig kidney responds to ET-1 by a direct constriction, which is modulated by nitric oxide but not eicosanoids (supported by the MRCC).

Animals↗
PubMed1999

A human anti-HIV autoantibody enhances EBV transformation and HIV infection.

A highly specific, human IgG mAb, F223, which reacts with both HIV-1-infected cells and uninfected lymphoid cells, has been derived. F223 reacts with gp120 but fails to neutralize viral infection. The antibody does enhance HIV-1 infection in a complement-dependent manner. The autoantigen recognized by F223 is expressed on a small percentage of T cells and NK cells and the majority of B cells. Immunoprecipitation demonstrates F223 reactivity with an as of yet unidentified 159-kDa protein in uninfected lymphoid cells. This reactivity with uninfected cells is inhibited by free gp120 demonstrating the cross-reactive nature of this antibody. The F223 light chain demonstrates strong homology to VLlambda2 family genes whereas the heavy chain is most homologous (84%) to the germline gene VH3-H.11. In vivo usage of VH3 family genes by F223 and an anti-HIV-1 (gp41) human mAb, 3D6, with related autoreactivity, suggests that VH3 sequences may be important components of potentially pathogenic human anti-HIV-1 envelope autoantibodies. F223 was isolated from an HIV-1 infected individual with lymphoma and in vitro F223 significantly enhances EBV transformation of normal B cells and increases immunoglobulin production without affecting B cell proliferation. Characterization of this antibody response may provide important insights and mechanistic information on HIV pathogenesis.

Antibodies, Blocking↗
PubMed1999

Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance.

We describe 4 cases of lysinuric protein intolerance, which all fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis. Mature histiocytes and neutrophil precursors participated in hemophagocytosis in the bone marrow. Moreover, serum levels of ferritin and lactate dehydrogenase were elevated, hypercytokinemia was present, and soluble interleukin-2 receptor levels were increased up to 18.6-fold. The diagnosis of lysinuric protein intolerance should therefore be considered in any patient presenting with hemophagocytic lymphohistiocytosis.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

[Neonatal alloimmune neutropenias. Importance of treatment with granulocyte colony-stimulating factor (G-CSF). Report of 2 new cases].

UNLABELLED: Alloimmune neonatal neutropenia is a rare event. Usually asymptomatic, it may however in some cases result in a severe sepsis. Treatment with recombinant granulocyte colony-stimulating factor (G-CSF) has been recently proposed. CASE REPORT: We report two new cases in infected newborns of a successful treatment of alloimmune neonatal neutropenia with G-CSF, resulting in complete neutrophil recovery in less than 72 hours. Moreover, the treatment was well tolerated. CONCLUSION: The analysis of these two cases and of those previously reported indicates that G-CSF represents the first-choice treatment in this affection when infectious signs are present in the neonate.

Age Factors↗
PubMed1999

Chediak-Higashi syndrome associated with maternal uniparental isodisomy of chromosome 1.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder (incidence around 1 in 106 births), characterised by a complex immunologic defects, reduced pigmentation, and presence of giant granules in many different cell types. It most likely results from defective organellar trafficking or protein sorting. The causative gene (LYST) has recently been identified and shown to be homologous to the beige locus in the mouse. CHS has always been reported associated with premature-termination-codon mutations in both alleles of LYST. We report a unique patient with CHS, who was homozygous for a stop codon in the LYST gene on chromosome 1 and who had a normal 46,XY karyotype. The mother was found to be a carrier of the mutation, whereas the father had two normal LYST alleles. Non-paternity was excluded by the analysis of microsatellite markers from different chromosomes. The results of 13 informative microsatellite markers spanning the entire chromosome 1 revealed that the proband had a maternal isodisomy of chromosome 1 encompassing the LYST mutation. The proband's clinical presentation also confirms the absence of imprinted genes on chromosome 1.

Alleles↗
PubMed1999

Mapping of chromosome 20 for loss of heterozygosity in childhood ALL reveals a 1,000-kb deletion in one patient.

The long arm of chromosome 20 displays recurrent loss of heterozygosity (LOH) for microsatellite markers in blast cells from children with acute lymphoblastic leukemia. To further characterize the region of deletion and to precisely establish its frequency, we searched for LOH in 103 children with ALL using polymorphic markers in the previously described region of interest, namely between D20S101 and D20S887. LOH was detected in nine patients (ie with a frequency of 8.7%). Interestingly, in one patient, a small deletion was found, flanked proximally by D20S850 and distally by M201, a dinucleotide repeat identified from chromosome 20 sequences. The distance between these two markers is approximately 1000 kb. The occurrence of non-random deletions of the long arm of chromosome 20 has previously been observed in myeloid malignancies (myeloproliferative disorders and myelodysplastic syndromes) in 5-10% of patients. The small deletion in our patient is located within the common region of deletion of myeloproliferative disorders suggesting that a tumor suppressor gene may be the common target of the deletions in various types of hematological malignancies.

Adolescent↗
PubMed1999

Minimal incidence of serum antibodies reactive with intact primary isolate virions in human immunodeficiency virus type 1-infected individuals.

Immunoglobulin G reactive with primary isolate virions was detected in 36% of serum samples from individuals infected with human immunodeficiency virus type 1. Of these individuals, serum samples from only 7% captured significant quantities of virus. Virion-specific antibody correlated with CD4 counts and, of more significance, primary isolate neutralization. Further dissection of this response should lead to the identification of antibodies and antigenic epitopes for vaccine purposes.

CD4 Lymphocyte Count↗