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Biomedical subjects

G Michel

Publications and source records attributed to G Michel.

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

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗
PubMed2004

[Thyroid dysfunction after haematopoietic stem cell transplantation during childhood].

UNLABELLED: To evaluate the percentage and risk factors of thyroid dysfunction in 79 children who underwent bone marrow transplantation in a single centre. PATIENTS AND METHODS: The mean age of the cohort was 6.8 and mean follow-up 5.5 years. The 79 patients were divided in two groups according to the pretransplant conditioning regimen: fractionated total body irradiation (TBI)(N=54), chemotherapy with Busulphan (N=25). Thyroid function was evaluated by thyroid-stimulating hormone (TSH) and free thyroxine (fT4) tests. Overt hypothyroidism was defined by low fT4 blood levels and TSH > 4 mU/l, and compensated hypothyroidism by normal fT4 index and TSH >4 mU/L. RESULTS: The six-year probability of hypothyroidism was 36 +/-6% for the whole group of 79 patients, 49 +/-8% after TBI and 9 +/-6% in the Busulphan group (P <0.001). Neither gender, nor primary disease, nor presence of graft versus host disease were found to be statistically significant for occurrence of hypothyroidism in the TBI group. However, a younger age seemed to influence statistically the 6-year probability of hypothyroidism in the TBI group: 59 +/-9% if age <7.7 years versus 34 +/-13% if age >7.7 years (P =0.02). CONCLUSION: A careful follow-up of thyroid function is recommended even without TBI conditioning regimen. Young age as a potential risk factor of hypothyroidism has never been described and needs to be studied in a larger cohort.

Adolescent↗
PubMed2004

Adhesion and proliferation of cells on new polymers modified biomaterials.

Up to today, several techniques have been used to maintain cells in culture for studying many aspects of cell biology and physiology. More often, cell culture is dependent on proper anchorage of cells to the growth surface. Poly-l-lysine is commonly used as adhesive molecule. In this study, we present, as an alternative to poly-l-lysine, new polymer film substrates, realized by electropolymerization of different monomers on fluorine-doped tin oxide (FTO) surfaces since electropolymerization is a good method to coat selectively metallic or semiconducting electrodes with polymer films. So, the adhesion, proliferation and morphology of rat neuronal cell lines were investigated on polymer treated surfaces. Several amine-based biocompatible polymers were tested: polyethyleneimine (PEI), polypropyleneimine (PPI), polypyrrole (PPy) and poly(p-phenylenediamine) (PPPD). These polymer films were coated on FTO surfaces by electrochemical oxidation. After 8 h in a culture medium, a high percentage of cells was found to be attached to PEI and PPI compared to the other polymers and to the reference surfaces (glass and FTO uncovered). After 24 and 72 h in the culture medium, cells were found to proliferate faster on PEI and PPI than on other polymers and reference surfaces. Consequently, cells have a greater fold expansion on PEI and PPI than on PPPD, PPy or glass and FTO uncoated. From these results, we deduce that PEI and PPI can be useful as coating surface to cultivate neuronal cells.

Amines↗
PubMed2003

Hematopoietic stem cell transplantation in patients with severe Langerhans cell histiocytosis and hematological dysfunction: experience of the French Langerhans Cell Study Group.

The aim of this study was to assess the results of hematopoietic stem cell transplantation (HSCT) in refractory Langerhans cell histiocytosis (LCH). Among 85 patients with LCH and hematological dysfunction diagnosed in France between 1987 and 2000, eight received HSCT in six institutions. Median age at diagnosis was 0.54 years. The median LCH activity score at diagnosis was 10 (range 3-20). All patients responded poorly to initial chemotherapy. At the time of HSCT, the median activity score was 16.5 (range 7-18). HSCT was autologous in three cases and allogeneic in five cases. The conditioning regimen consisted of TBI in two cases and chemotherapy alone in six cases. Conditioning had to be attenuated in two patients. All patients had persistent active disease after autologous HSCT, which was fatal in two cases and controlled by chemotherapy in one case. After allogeneic HSCT, two patients died from toxicity and three had complete responses; two patients had had no recurrences after 21 months and 7 years of follow-up, while the other patient relapsed and died from sepsis related to splenectomy. HSCT for refractory LCH can thus be highly toxic but can also achieve sustained disease control.

Chimera↗
PubMed2003

Allogeneic bone marrow transplantation for chronic myeloid leukemia in childhood: a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

To determine the results of allogeneic hematopoietic stem cell (HSC) transplantation for chronic myelogenous leukemia (CML) at various stages of the disease in children, a retrospective analysis was carried out on the outcome of transplants performed on 76 children and teenagers with CML between 1982 and 1998. In all, 60 patients were transplanted from a matched sibling donor (MSD) and 16 from a matched unrelated donor (MUD). There was a higher incidence of acute graft-versus-host disease after MUD transplantation (P<10(-3)). The main cause of death was transplant-related toxicity in both groups. In MSD recipients, the probability of relapse at 5 years for patients transplanted in the first chronic phase was lower than in patients transplanted in the advanced phase (relative risk (rr)=5.90; 95% confidence interval (CI), 1.85-18.82, P<0.01). The estimated 5-year event-free survival (EFS) rate was higher after MSD vs MUD transplantation (61% (95% CI, 48-73%) vs 27% (95% CI, 4-49%), rr=0.25, P<10(-3)). In children transplanted from MSD, the 5-year EFS was higher when transplantation was performed in the first chronic phase vs the advanced phases (73% (95% CI, 59-87%) vs 32% (95% CI, 10-54%), P<10(-3)). Disease status at transplantation was the unique factor influencing survival in patients undergoing transplantation from MSD with a better outcome for those transplanted in the first chronic phase. Allogeneic HSC offers a possibility of curing childhood CML with a significant advantage for patients transplanted in chronic phase using a human leukocyte antigen-identical sibling donor.

Adolescent↗
PubMed2002

A novel mechanism for thalassaemia intermedia.

Thalassaemia intermedia is a moderate form of thalassaemia resulting from various genetic defects. We report an undescribed mechanism leading to this condition: a somatic deletion of the beta-globin gene in the haemopoietic lineage of a heterozygous beta-thalassaemic patient. We did molecular studies and haemoglobin analysis of the patient and his parents. We found that the deletion gives rise to a mosaic of cells with either one or no functional beta-globin gene and it extends to a region of frequent loss of heterozygosity called LOH11A, which is located close to the beta-globin locus. Thus, loss of heterozygosity can be a cause of non-malignant genetic disease.

Anemia↗
PubMed2002

Cross-cultural assessment of childhood temperament. A confirmatory factor analysis of the French Emotionality Activity and Sociability (EAS) questionnaire.

The Emotionality Activity Sociability (EAS) questionnaire focuses on heritable individual differences in reactivity and behavior which are often referred to in developmental temperament research. Psychometric properties of the French version of EAS were examined in a sample of 197 school-children aged six to 12 years. Parents, teachers and children aged nine years and more completed parallel forms of the EAS questionnaire. Confirmatory factor analysis was used to examine the fit between the original factors and the data. Internal consistency of each subscale, inter-rater and external validity were also examined. Children-rated EAS showed the best indices of fit between the four hypothesized factors and the data, but internal consistency was generally lower than in adult-rated questionnaires. Shyness and sociability showed significant overlap in both parent and teacher-rated EAS. The low concordance between child and adult-ratings indicates that temperament evaluation and interpretation of items may be influenced by subjective and/or developmental factors. Results are discussed in the perspective of validity versus cross-cultural comparability of temperament measurement. The theoretical four-factor structure was not completely replicable in our sample.

Child↗
PubMed2002

[Progressive multifocal leukoencephalopathy revealing AIDS in a 13-year-old girl].

CASE REPORT: A 13-year-old girl with an immunosuppression developed a right hemiparesis and a cerebellar syndrome. She was seropositive for HIV. A progressive multifocal leukoencephalopathy (PML) was suspected because of white matter lesions (MRI) and established on detection of JC virus in CSF by polymerase chain reaction (PCR). In spite of highly active antiretroviral treatment (HAART) and cidofovir, she died three months later. CONCLUSION: Late AIDS diagnosis was established during a neurological complication, 13 years after a neonatal transmission. PML caused by JC opportunistic virus still has a poor prognosis.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Transduction pathways involved in Hypoxia-Inducible Factor-1 phosphorylation and activation.

Hypoxia-Inducible Factor-1 (HIF-1) is a transcription factor which is activated by hypoxia and involved in the adaptative response of the cell to oxygen deprivation. During hypoxic stress, HIF-1 triggers the overexpression of genes coding for glycolytic enzymes and angiogenic factors. To be active HIF-1 must be phosphorylated. HIF-1 is a substrate for various kinase pathways including PI-3K and the MAP kinases ERK and p38. Several transduction pathways have been proposed which act downstream of putative oxygen sensors and lead to the activation of these kinases. In this review, we summarize some of the latest advances describing the possible signaling pathways leading to HIF-1 phosphorylation and subsequent activation. The physiological relevance of these regulations is also discussed.

Angiogenesis Inhibitors↗
PubMed2001

The iota-carrageenase of Alteromonas fortis. A beta-helix fold-containing enzyme for the degradation of a highly polyanionic polysaccharide.

Carrageenans are gel-forming hydrocolloids extracted from the cell walls of marine red algae. They consist of d-galactose residues bound by alternate alpha(1-->3) and beta(1-->4) linkages and substituted by one (kappa-carrageenan), two (iota-carrageenan), or three (lambda-carrageenan) sulfate-ester groups per disaccharide repeating unit. Both the kappa- and iota-carrageenan chains adopt ordered conformations leading to the formation of highly ordered aggregates of double-stranded helices. Several kappa-carrageenases and iota-carrageenases have been cloned from marine bacteria. Kappa-carrageenases belong to family 16 of the glycoside hydrolases, which essentially encompasses polysaccharidases specialized in the hydrolysis of the neutral polysaccharides such as agarose, laminarin, lichenan, and xyloglucan. In contrast, iota-carrageenases constitute a novel glycoside hydrolase structural family. We report here the crystal structure of Alteromonas fortis iota-carrageenase at 1.6 A resolution. The enzyme folds into a right-handed parallel beta-helix of 10 complete turns with two additional C-terminal domains. Glu(245), Asp(247), or Glu(310), in the cleft of the enzyme, are proposed as candidate catalytic residues. The protein contains one sodium and one chloride binding site and three calcium binding sites shown to be involved in stabilizing the enzyme structure.

Alteromonas↗
PubMed2001

Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia.

In order to compare the outcomes of unrelated umbilical cord blood transplants (UCBTs) or bone marrow transplants, 541 children with acute leukemia (AL) transplanted with umbilical cord blood (n = 99), T-cell-depleted unrelated bone marrow transplants (T-UBMT) (n = 180), or nonmanipulated (UBMT) (n = 262), were analyzed in a retrospective multicenter study. Comparisons were performed after adjustment for patient, disease, and transplant variables. The major difference between the 3 groups was the higher number in the UCBT group of HLA mismatches (defined by serology for class I and molecular typing for DRB1). The donor was HLA mismatched in 92% of UCBTs, in 18% of UBMTs, and in 43% of T-UBMTs (P <.001). Other significant differences were observed in pretransplant disease characteristics, preparative regimens, graft-versus-host disease (GVHD) prophylaxis, and number of cells infused. Nonadjusted estimates of 2-year survival and event-free survival rates were 49% and 43%, respectively, in the UBMT group, 41% and 37% in the T-UBMT group, and 35% and 31% in the UCBT group. After adjustment, differences in outcomes appeared in the first 100 days after the transplantation. Compared with UBMT recipients, UCBT recipients had delayed hematopoietic recovery (Hazard ratio [HR] = 0.37; 95% confidence interval [95CI]: 0.27-0.52; P <.001), increased 100 day transplant-related mortality (HR = 2.13; 95CI: 1.20-3.76; P <.01) and decreased acute graft-versus-host disease (aGVHD) (HR = 0.50; 95CI: 0.34-0.73; P <.001). T-UBMT recipients had decreased aGVHD (HR = 0.25; 95CI: 0.17-0.36; P <.0001) and increased risk of relapse (HR = 1.96; 95CI: 1.11-3.45; P =.02). After day 100 posttransplant, the 3 groups achieved similar results in terms of relapse. Chronic GVHD was decreased after T-UBMT (HR = 0.21; 95CI: 0.11-0.37; P <.0001) and UCBT (HR = 0.24; 95CI: 0.01-0.66; P =.002), and overall mortality was higher in T-UBMT recipients (HR = 1.39; 95CI: 0.97-1.99; P <.07). In conclusion, the use of UCBT, as a source of hematopoietic stem cells, is a reasonable option for children with AL lacking an acceptably matched unrelated marrow donor.

Analysis of Variance↗
PubMed2001

c-JUN gene induction and AP-1 activity is regulated by a JNK-dependent pathway in hypoxic HepG2 cells.

Hypoxia is an important pathophysiological stress that occurs during blood vessel injuries and tumor growth. It is now well documented that hypoxia leads to the activation of several transcription factors which participate in the adaptive response of the cells to hypoxia. Among these transcription factors, AP-1 is rapidly activated by hypoxia and triggers bFGF, VEGF, and tyrosine hydroxylase gene expression. However, the mechanisms of AP-1 activation by hypoxia are not well understood. In this report, we studied the events leading to AP-1 activation in hypoxia. We found that c-jun protein accumulates in hypoxic HepG2 cells. This overexpression is concomitant with c-jun phosphorylation and JNK activation. Moreover, we showed that AP-1 is transcriptionally active. We also observed that AP-1 transcriptional activity is inhibited by a MEKK1 dominant negative mutant. Moreover, the MEKK1 dominant negative mutant as well as deletion of the AP-1 binding sites within the c-jun promoter inhibited the c-jun promoter activation by hypoxia. All together, these results indicate that, in hypoxic HepG2 cells, AP-1 is activated through a JNK-dependent pathway and that it is involved in the regulation of the c-jun promoter, inducing a positive feedback loop on AP-1 activation via c-jun overexpression.

Cell Hypoxia↗
PubMed2001

[Glucose-6-phosphate dehydrogenase et neonatal jaundice].

OBJECTIVE: Since 1986, quantification of G6PD activity has been a routine test for all babies born at the public maternity hospitals of Marseilles. The objective of our study was to determine the prevalence of G6PD deficiency in the population tested and to evaluate the relative risk of neonatal jaundice in newborns with G6PD deficiency. METHODS: Neonatal screening is performed on cord blood by spectrophotometric measurements of G6PD activity. A group of 7779 newborns was studied retrospectively. The occurrence of neonatal jaundice was evaluated in 85 children with G6PD deficiency and compared to 85 children with normal G6PD activity. RESULTS: The incidence of G6PD deficiency in male newborns was found to be 2.1%. The relative risk for neonatal jaundice in the G6PD deficient population compared to the non-deficient population is estimated to be 2.6. CONCLUSION: Neonatal jaundice with pathological hyperbilirubinemia develops more frequently in cases of G6PD deficiency. The early characterization of G6PD activity provides an etiological diagnosis for neonatal jaundice, as well as the opportunity to give the newborn's family information concerning hemolytic crisis prevention.

Cohort Studies↗
PubMed2001

The kappa-carrageenase of P. carrageenovora features a tunnel-shaped active site: a novel insight in the evolution of Clan-B glycoside hydrolases.

BACKGROUND: kappa-carrageenans are gel-forming, sulfated 1,3-alpha-1,4-beta-galactans from the cell walls of marine red algae. The kappa-carrageenase from the marine, gram-negative bacterium Pseudoalteromonas carrageenovora degrades kappa-carrageenan both in solution and in solid state by an endoprocessive mechanism. This beta-galactanase belongs to the clan-B of glycoside hydrolases. RESULTS: The structure of P. carrageenovora kappa-carrageenase has been solved to 1.54 A resolution by the multiwavelength anomalous diffraction (MAD) method, using a seleno-methionine-substituted form of the enzyme. The enzyme folds into a curved beta sandwich, with a tunnel-like active site cavity. Another remarkable characteristic is the presence of an arginine residue at subsite -1. CONCLUSIONS: The crystal structure of P. carrageenovora kappa-carrageenase is the first three-dimensional structure of a carrageenase. Its tunnel-shaped active site, the first to be reported for enzymes other than cellulases, suggests that such tunnels are associated with the degradation of solid polysaccharides. Clan-B glycoside hydrolases fall into two subgroups, one with catalytic machinery held by an ancestral beta bulge, and the other in which it is held by a regular beta strand. At subsite -1, all of these hydrolases exhibit an aromatic amino acid that interacts with the hexopyranose ring of the monosaccharide undergoing catalysis. In addition, in kappa-carrageenases, an arginine residue recognizes the sulfate-ester substituents of the beta-linked kappa-carrageenan monomers. It also appears that, in addition to the nucleophile and acid/base catalysts, two other amino acids are involved with the catalytic cycle, accelerating the deglycosylation step.

Alteromonas↗
PubMed2001

Nutrient intakes as predictors of body weight in European people with type 1 diabetes.

BACKGROUND: Overweight and obesity are also found among persons with type 1 diabetes. OBJECTIVE: The present study examined which nutrients predict the body mass index (BMI), the waist-to-hip ratio (WHR) and the waist circumference (WC) of European persons with type 1 diabetes. DESIGN: Cross-sectional, clinic-based study (EURODIAB Complications Study). SUBJECTS AND METHODS: Nutrient intakes (assessed by a 3-day dietary record) predicting measures of body weight (BMI, WHR and WC) were determined by stepwise forward regression analysis in 1458 males and 1410 females with type 1 diabetes (P< or =0.05 for inclusion). RESULTS: In men, a higher carbohydrate intake was a significant independent predictor for lower levels of BMI, WHR and WC, an increased saturated fat intake and a lower intake of cereal fibre predicted a higher WHR, a higher monounsaturated fat intake and a lower glycaemic index of the diet determined lower levels of WHR and WC, and a moderate consumption of alcohol determined an increased WC. In women, a higher carbohydrate intake predicted a lower BMI and a thinner WC, no alcohol consumption determined a lower BMI, and an increased intake of saturated fat and a lower consumption of cereal fibre were significant independent predictors for a higher WHR. CONCLUSIONS: A modified fat intake, an increase of carbohydrate and cereal fibre intake and a preferred consumption of low glycaemic index foods are independently related to lower measures of body weight in European persons with type 1 diabetes.

Adult↗
PubMed2001

Factors affecting lymphocyte subset reconstitution after either related or unrelated cord blood transplantation in children -- a Eurocord analysis.

Immune recovery after cord blood transplantation (CBT) is of concern owing to the low number of lymphocytes transferred with the graft and their immaturity. Risk factors influencing lymphocyte subset reconstitution related to disease, patient, donor and transplant were studied in 63 children (< 16 years), given either related (n = 14) or unrelated (n = 49) CBT for malignant (n = 33) or non-malignant diseases (n = 30). Only children with sustained myeloid engraftment were analysed. Absolute numbers of T (CD3(+), CD4(+), CD8(+)), B and natural killer (NK) cells were reported 2--3, 6, 9, 12 and 12--24 months after CBT. Median patient age was 4.0 years (0--15) and median follow-up was 23 months (1.7--61.0). Twenty-six patients received human leucocyte antigen (HLA)-matched CBT and 37 received HLA-mismatched CBT. The median number of nucleated cells (NCs) collected/recipient weight was 6.1 x 10(7)/kg. In this selected population, the estimate 2 year survival was 85%. Lymphocyte reconstitution (defined as the median time to reach the normal value of age-matched healthy children) was 3, 6 and 8 months for NK, B and CD8(+) cells, while it was 11.7 months for both CD3(+) and CD4(+) lymphocytes. In the multivariate analysis, factors favouring T-cell recovery were: related donor (P = 0.002); higher NCs/kg (P = 0.005) and recipient cytomegalovirus (CMV)-positive serology (P = 0.04). Presence of acute graft-versus-host disease (GVHD) delayed T-cell recovery (P = 0.04). To summarize, in children with sustained myeloid engraftment the concern that lymphocyte recovery after CBT could be delayed does not appear to be substantiated by our results.

Adolescent↗