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Biomedical subjects

A Robert

Publications and source records attributed to A Robert.

At least 19 recordsLinked to original sources
PubMed2006

HIGM syndrome caused by insertion of an AluYb8 element in exon 1 of the CD40LG gene.

A new mutation of the CD40LG gene that encodes the CD40 ligand molecule was characterized in a young patient harboring a hyper-IgM with immunodeficiency syndrome. Inactivation of CD40LG gene resulted from the insertion of an AluYb8 element in exon 1 responsible for a total deficiency of CD40 ligand expression by T lymphocytes. Maternal transmission of the X-linked mutation was confirmed by gene-specific polymerase chain reaction. This is the 17th case report concerning a human genetic disease caused by an Alu element insertion in a coding sequence.

Alu Elements↗
PubMed2006

Biological monitoring of workers exposed to 4,4'-methylenediphenyl diisocyanate (MDI) in 19 French polyurethane industries.

OBJECTIVES: To study the range of urinary levels of 4,4'-methylenedianiline (MDA), a metabolite of methylenediphenyl diisocyanate (MDI), across factories in the polyurethane industries and to evaluate the validity of this biomarker to assess MDI occupational exposure. METHODS: Workers exposed to MDI, as well as non-occupationally exposed subjects, were studied and pre- and post-shift urine samples were collected from 169 workers of 19 French factories and 120 controls. Details on work activities and practices were collected by a questionnaire and workers were classified into three job categories. The identification and quantification of the total urinary MDA were performed by high-performance liquid chromatography with electrochemical detection (HPLC/EC). RESULTS: For all the factories, MDA was detectable in 73% of the post-shift urine samples. These post-shift values, in the range of <0.10 (detection limit)-23.60 microg/l, were significantly higher than those of the pre-shift samples. Urinary MDA levels in the control group were in the range of < 0.10-0.80 microg/l. The degree of automation of the mixing operation (polyols and MDI) appears as a determinant in the extent of exposure levels. The highest amounts of MDA in urine were found in the spraying or hot processes. The excretion levels of the workers directly exposed to the hardener containing the MDI monomer were significantly higher than those of the other workers. In addition, skin exposure to MDI monomer or to polyurethane resin during the curing step were always associated with significant MDA levels in urine. CONCLUSIONS: Total MDA in post-shift urine samples is a reliable biomarker to assess occupational exposure to MDI in various industrial applications and to help factories to improve their manufacturing processes and working practices. A biological guiding value not exceeding 7 microg/l (5 microg/g creatinine) could be proposed in France.

Environmental Monitoring↗
PubMed2006

Regions of alpha-amino-5-methyl-3-hydroxy-4-isoxazole propionic acid receptor subunits that are permissive for the insertion of green fluorescent protein.

The green fluorescent protein can be fused to the ends of a mature glutamate receptor subunit to produce functional, fluorescent receptors. However, there are good reasons to search for internal regions of receptor subunits that can tolerate green fluorescent protein insertion. First, internal insertions of green fluorescent protein may produce functional, fluorescent subunits that traffic more correctly. Second, fluorescent proteins inserted near interacting surfaces of subunits could potentially create reagents suitable for fluorescence resonance energy transfer measurements. Finally, internal green fluorescent protein insertions could potentially produce subunits capable of signaling conformational changes through intrinsic changes in fluorescence intensity. To identify regions of receptor subunits that are permissive for green fluorescent protein insertion, we used a series of recombinant transposons to create fluorescent protein insertions in three alpha-amino-5-methyl-3-hydroxy-4-isoxazole propionic acid receptor subunits. A combined analysis of the relative fluorescence intensity and glutamate-gated ion channel function of 69 different green fluorescent protein fusion proteins identified permissive zones for the creation of bright and fully functional receptor subunits in the C-terminal portion of the amino terminal domain, the intracellular tail of the carboxy terminal domain, and within the pore-forming regions of the channel.

Amino Acid Sequence↗
PubMed2006

Antioxidant status and oxidative stress in professional rugby players: evolution throughout a season.

Physical training is known to increase the antioxidant defence system and reduce exercise-induced oxidative stress. However, intense physical aerobic and anaerobic training and competition such as those imposed on professional rugby players, can induce an increase of oxidative stress which can be implicated with the arrival of overtraining. The aim of this study was to test the effect of training and competition load on oxidative stress, antioxidant status, haematological, and cell damage markers in high-level rugby players during a competitive season. Blood samples were collected four times in one year. Oxidative stress (Rmax), antioxidant (vitamin E, uric acid, TAC, and lag phase), haematological (neutrophils and monocytes) and biochemical (CK and myoglobin) parameters, as well as training and competition load, and competition results were measured. Intense periods of training and competition (T1 and T4) induced a significant higher maximum rate of conjugated dienes oxidation (+67.2% in T1 and +40.6% in T4) compared to those observed at the reference time (T3). Those periods also induced an increase in uric acid (+6.9% and 3.2%), and inflammatory markers such as monocytes (+13.3% and 10.7%). On the other hand, vitamin E (-8.7% in T1) and lag phase (-23.0% and -14.7%) were lower during these periods showing a possible training-induced antioxidant down-regulation. The less intense period of training (T2) was accompanied by lower neutrophils (-8.5%), CK (-53.7%), and myoglobin (-16.2%) values. The results suggest that oxidative stress and antioxidant measurement are significant in the biological follow-up of athletes.

Adult↗
PubMed2005

Genetic abnormalities associated with the t(12;21) and their impact in the outcome of 56 patients with B-precursor acute lymphoblastic leukemia.

The ETV6/RUNX1 rearrangement is found in 20-30% of children with B-cell precursor acute lymphoblastic leukemia and is associated with a good outcome. To determine the cytogenetic and molecular abnormalities associated with the ETV6/RUNX1 rearrangement and the influence of this rearrangement in patients' evolution, we analyzed the molecular cytogenetic profiles of 56 children with this rearrangement and B-cell precursor acute lymphoblastic leukemia. Secondary changes detected with conventional cytogenetics and with fluorescence in situ hybridization were found in 71.4% of cases, the most frequent being the loss of the normal ETV6 allele, 12p aberrations, duplication of the fusion gene, and trisomy 21, as in replicating the results of previous studies. In this preliminary series, with a mean follow-up of 69.3 months, secondary abnormalities did not influence patients' outcome. It seems therefore that the prognostic value of the t(12;21) does not vary and that ETV6/RUNX1 rearrangement is an independent indicator of good prognosis.

Child↗
PubMed2005

Bulk milk somatic cell counts and bovine viral diarrhoea virus (BVDV) infection in 7252 dairy herds in Brittany (western France).

Variations in test-day bulk milk somatic cell count (BMSCC) according to bovine viral diarrhoea virus (BVDV) infection status of the herd were quantified. Infection statuses were defined, based on bulk-milk antibodies measured twice 4 months apart. On each test-day, BMSCC was calculated as the weighted mean of the individual cow-level somatic cell counts. A total of 97,985 test-days in 7252 herds were considered. The effect of the BVDV-infection on BMSCC was assessed using mixed linear models, controlling for herd (random), proportion of primiparous cows and average days in milk on test-day. Considering test-days contemporary to the BVDV-status definition-period, the increase in BMSCC was 12,000 (P<0.001), 27,000 (P<0.001) and 6000 (P=0.97) cells/ml in past-infected recently recovered, past-but-still-infected and recently infected herds respectively, compared with not recently infected herds. A carry-over effect (at least 1 year) of BVDV-infection on BMSCC was also evidenced in past-infected recently recovered, past-but-still-infected and recently infected herds.

Animals↗
PubMed2005

A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias.

Chromosomal translocations with breakpoints in T-cell receptor (TCR) genes are recurrent in T-cell malignancies. These translocations involve the TCRalphadelta gene (14q11), the TCRbeta gene (7q34) and to a lesser extent the TCRgamma gene at chromosomal band 7p14 and juxtapose T-cell oncogenes next to TCR regulatory sequences leading to deregulated expression of those oncogenes. Here, we describe a new recurrent chromosomal inversion of chromosome 7, inv(7)(p15q34), in a subset of patients with T-cell acute lymphoblastic leukemia characterized by CD2 negative and CD4 positive, CD8 negative blasts. This rearrangement juxtaposes the distal part of the HOXA gene cluster on 7p15 to the TCRbeta locus on 7q34. Real time quantitative PCR analysis for all HOXA genes revealed high levels of HOXA10 and HOXA11 expression in all inv(7) positive cases. This is the first report of a recurrent chromosome rearrangement targeting the HOXA gene cluster in T-cell malignancies resulting in deregulated HOXA gene expression (particularly HOXA10 and HOXA11) and is in keeping with a previous report suggesting HOXA deregulation in MLL-rearranged T- and B cell lymphoblastic leukemia as the key factor in leukaemic transformation. Finally, our observation also supports the previous suggested role of HOXA10 and HOXA11 in normal thymocyte development.

Adolescent↗
PubMed2005

Value of intravenous 6-mercaptopurine during continuation treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: final results of a randomized phase III trial (58881) of the EORTC CLG.

Between November 1990 and November 1996, EORTC Children Leukemia Group conducted a randomized trial in de novo acute lymphoblastic leukemia and lymphoblastic non-Hodgkin's lymphoma patients using a Berlin-Frankfurt-Munster protocol to evaluate the monthly addition of intravenous 6-mercaptopurine (i.v. 6-MP) (1 g/m(2)) to conventional continuation therapy comprising per oral MTX weekly and 6-MP daily. Only during the first 18 months of the randomization period, 6-MP p.o. was interrupted for 1 week after each i.v. 6-MP. A total of 877 patients was randomized to either no i.v. 6-MP (Arm A) or additional i.v. 6-MP (Arm B). A total of 217 relapses (91 in Group A vs 128 in Group B) and 13 deaths in CR (5 vs 8) were reported; a total of 134 patients (55 vs 79) died. The median follow-up was 7.6 years. At 8 years, the disease-free survival rate was lower (P=0.005) in Arm B (69.1% (s.e.=2.2%)) than in Arm A (77.9% (s.e.=2.0%)), and the hazard ratio was 1.45 (95% CI 1.12-1.89). In conclusion, as delivered in this study, i.v. 6-MP was detrimental to event-free survival.

Adolescent↗
PubMed2004

ETV6/RUNX1 rearrangement in childhood B-precursor acute lymphoblastic leukemia with normal karyotypes or without cytogenetic results.

The ETV6/RUNX1 rearrangement (also known as TEL/AML1) was evaluated in 39 children with B-precursor acute lymphoblastic leukemia (ALL) who had a normal karyotype or lack of mitoses. Forty-one point six percent of patients with normal karyotypes and 66.6% of patients without mitoses presented with the ETV6/RUNX1 rearrangement. In addition to this rearrangement, eight patients showed loss of the normal ETV6 allele; of three patients without mitoses, two showed an extra signal of the RUNX1 gene and the third showed the fusion gene duplicated and loss of the normal ETV6 allele. One patient without the ETV6/RUNX1 rearrangement and without mitoses showed two extra signals of the RUNX1 gene.

Child↗
PubMed2004

Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy.

PURPOSE: To determine the results of treatment combining all-trans-retinoic acid (ATRA) and chemotherapy (CT) in childhood acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Children (< 18 years) with newly diagnosed APL were included in the APL93 trial, treated by ATRA followed or combined with daunorubicin-cytarabine, and then randomly assigned between no maintenance, intermittent ATRA, continuous CT, or both. RESULTS: Of the 576 patients included in APL93 trial, 31 (5%) were children, including 22 girls (71%) and nine boys (29%). Thirty of the children (97%) obtained complete remission (CR). ATRA syndrome occurred in four children (13%), who all achieved CR, and headaches occurred in 12 children (39%), with signs of pseudotumor cerebri in five children (16%). Seven patients (23%) relapsed. None of the eight patients who received both ATRA and CT for maintenance relapsed. All relapsing patients achieved a second CR. Twenty-two patients remained in first CR after 43+ to 96+ months, six remained in second CR after 17+ to 66+ months, and three patients had died. The 5-year event-free survival (EFS), relapse, and overall survival rates were 71%, 27%, and 90%, respectively. No difference between adults and children included in the APL93 trial was seen for CR rate, 5-year relapse rate, EFS, and overall survival, but significantly better survival was seen in children after adjustment on WBC counts (P =.02) and incidence of microgranular M3 variant (P =.04). CONCLUSION: ATRA combined with CT for induction and also probably for maintenance provides as favorable results in children with APL as in adults and currently constitutes the reference first-line treatment in both age groups.

Adolescent↗
PubMed2004

High incidence of complications after 2-chloro-2'-deoxyadenosine combined with cyclophosphamide in patients with advanced lymphoproliferative malignancies.

The combination of purine analogs with alkylating agents is able to produce a synergistic antitumoral effect. However, the addition of immunosuppressive and DNA-targeting agents might increase purine analog-related complications. The risk for serious complications was evaluated in 38 patients treated with 2-chloro-2'-deoxyadenosine (CDA) and cyclophosphamide (CP). The diagnoses were chronic lymphocytic leukemia (CLL) in 15, Waldenström's macroglobulinemia in 4, mantle cell lymphoma in 6, follicular non-Hodgkin's lymphoma (NHL) in 10, and other low-grade NHL in 3 patients. All patients were pretreated (median: 2 lines, range: 1-5) and 23 (61%) were refractory. The patients received a median of two courses (range: 1-5) of 5.6 mg/m(2) CDA, followed by a median of 200 mg/m(2) CP, for 3 days. The response rate was 51% [complete remission (CR): 14%, partial remission (PR): 38%]. Grade 3/4 infections occurred in 16 (42%) patients. Dose-limiting cytopenias were seen in 22 (58%) patients. In 12 (32%) patients, autoimmune manifestations developed requiring treatment in most of them. Second cancers arose in five (13%) patients (myelodysplastic syndrome/acute myelocytic leukemia in three, lung cancer in two). Multivariate analysis showed that cytopenias, gender (F), prior radiotherapy, and age (>65 years) predicted for the complications seen after CDA-CP. To conclude, because of the high incidence of complications, caution is warranted in selecting patients with advanced lymphoid malignancies for the CDA-CP protocol.

Adult↗
PubMed2004

Infectious diseases in the first year of life, perinatal characteristics and childhood acute leukaemia.

The objective of the present study was to investigate the role of early common infections and perinatal characteristics in the aetiology of childhood common leukaemia. A case-control study was conducted from 1995 to 1998 in France, and included 473 incident cases of acute leukaemia (AL) (408 acute lymphoblastic leukaemia (ALL), 65 acute myeloid leukaemia (AML) age-, sex- and region-matched with 567 population-based controls. Data on the medical history of the child and his/her environment were collected using self-administered questionnaires. Analyses were conducted using nonconditional logistic regression. A slight negative association with early infections was observed (OR=0.8; 95% CI (0.6-1.0)). The association was stronger for early gastrointestinal infections. Early day-care was found to be associated with a decreased risk of AL (OR=0.6; 95% CI (0.4-0.8) and OR=0.8; 95% CI (0.5-1.2) for day-care starting before age 3 months and between 3 and 6 months, respectively). No association with breast-feeding was observed, irrespective of its duration. A birth order of 4 or more was associated with a significantly increased risk of AL (OR=2.0; 95% CI (1.1-3.7) with ALL). A history of asthma was associated with a decreased risk of ALL (OR 0.5; 95% CI (0.3-0.90). Although the results regarding birth order and breast-feeding do not fit with Greaves' hypothesis, the study supports the hypothesis that early common infections may play a protective role in the aetiology of childhood leukaemia, although this effect was not more marked for common ALL.

Acute Disease↗
PubMed2004

Large scale assessment of the effect associated with bovine viral diarrhoea virus infection on fertility of dairy cows in 6149 dairy herds in Brittany (Western France).

This study aimed at quantifying on a large scale the risk of both three-week-return-to-service and late-return-to-service for dairy cows according to the BVDV-infection status of the herds. Three-week- and late-returns-to-service were defined as a repeat service occurring respectively from 19 to 25 days and after 25 days following a first or a second service. The level of BVDV-specific-antibodies in bulk tank milk were measured four times at four months intervals by a blocking ELISA test to define five BVDV-infection-herd-statuses: (i) presumed non-infected herds for a long time, (ii) presumed not-recently-infected herds, (iii) presumed past-infected-recently-recovered herds, (iv) presumed past-steadily-infected herds, (v) presumed recently-infected herds. A total of 150,854 AIs from 122,697 cows in 6149 herds was included in the analysis. The risk of return-to-service was assessed using logistic regression and survival analysis models. The BVDV-infection-herd-status was not significantly associated with the risk of 3-week-return-to-service, but significantly with that of late-return-to-service. Cows in herds presumed past-infected-recently-recovered, past-steadily-infected, or recently-infected had a significantly higher risk of late-return-to-service (relative risk of 1.03, 1.11, 1.12, respectively) compared with cows in herds presumed not-recently-infected. Risk of late-return-to-service was not significantly different in cows from herds presumed non-infected for a long time or not-recently-infected. In conclusion, BVDV-infection was found to mainly increase the risk of embryonic and foetal death.

Animals↗
PubMed2004

Establishment of a novel anaplastic large-cell lymphoma-cell line (COST) from a 'small-cell variant' of ALCL.

Anaplastic large-cell lymphoma (ALCL) is a distinct biological and cytogenetic entity with a broad spectrum of morphological features (common type, small-cell variant and lymphohistiocytic variant). Few cell lines of ALCL are available and they all originate from primary tumors demonstrating the common type morphology (ie large-sized lymphoma cells). We established a new ALCL cell line (COST) from the peripheral blood of a patient with a small-cell variant of ALCL, at diagnosis. Cells growing in vitro and in SCID mice consisted of two populations, that is, small- and large-sized cells as seen in the patient's tumor. Both large and small malignant cells were positive for CD43/MT1 T-cell associated antigen, perforin, granzyme B and TIA-1, but negative for CD2, CD3, CD5, CD7, CD4 and CD8 antigens. Standard cytogenetic studies as well as multiplex FISH confirmed the presence of the canonical t(2;5)(p23;q35) translocation, but also revealed additional numerical and structural abnormalities. The COST cell line is the first ALCL small-cell variant cell line, and thus provides a potentially useful tool for further functional and molecular studies that should improve our understanding of the small-cell variant of ALCL, which is more frequently complicated by a leukemic phase.

Animals↗
PubMed2004

Four new cases of stomatin-deficient hereditary stomatocytosis syndrome: association of the stomatin-deficient cryohydrocytosis variant with neurological dysfunction.

This report concerns congenitally Na(+)-K(+) leaky red cells of the 'hereditary stomatocytosis' class. Three new isolated cases and one new pedigree are described, and one previously reported case is expanded. In all cases, Western blotting of red cell membranes revealed a deficiency in the 32 kDa membrane protein, stomatin. All showed pronounced cation leaks at 37 degrees C with markedly abnormal intracellular Na(+) and K(+) concentrations, like all other such stomatin-deficient cases. Consistent with recent findings in two previously described British pedigrees, immunocytochemistry demonstrated that the deficiency of stomatin was not complete. On typical blood films, some red cells showed positive stomatin immunoreactivity, while most were negative, although in one case only a minority were negative. All platelets and neutrophils were stomatin positive. The cases differed markedly between themselves with regard to the temperature dependence of the passive leak to K(+). Three showed a simple monotonic temperature dependence, while two showed a minimum at around 20-25 degrees C, such that the cells were extremely leaky at 0 degrees C, giving the phenotype known as 'cryohydrocytosis'. These patients are the only two known cases of stomatin-deficient cryohydrocytosis. Both showed a congenital syndrome of mental retardation, seizures, cataracts and massive hepatosplenomegaly, probably defining a new haemato-neurological syndrome.

Adult↗
PubMed2004

Salivary testosterone and cortisol in rugby players: correlation with psychological overtraining items.

BACKGROUND: A psychocomportemental questionnaire has been devised by the consensus group of the Société Française de Médecine du Sport to characterise and quantify, using a list of functional and psychocomportemental signs, a state of "staleness", for which no biological indicator is unanimously recognised. OBJECTIVES: To determine the relation between this diagnostic method and two hormones (cortisol and testosterone) often used as indicators of a state of fitness or staleness. METHODS: The subjects were young rugby players. They were asked to complete the overtraining questionnaire and gave three saliva samples (at 8 am, 11 am, and 5 pm) during a rest day. Concentrations of cortisol and testosterone in the saliva were determined by radioimmunoassay. RESULTS: A preferential relation was found between the questionnaire score and testosterone concentration but not between the questionnaire score and cortisol concentration. CONCLUSIONS: The questionnaire may be a useful tool for screening subjects at risk of overtraining. Testosterone concentration is influenced by tiredness, and is therefore a valid marker of tiredness.

Adolescent↗
PubMed2003

Behaviour of saliva cortisol [C], testosterone [T] and the T/C ratio during a rugby match and during the post-competition recovery days.

Competition is a more demanding situation than other strenuous exercise of equivalent duration; it results in stronger physiological changes. The object of this study was to get information on the duration of the recovery period by measuring changes of saliva cortisol [C], testosterone [T] and their ratio T/C in a group of international rugby players ( n=20) during the week following a rugby match (6 days). Using non-invasive saliva assays, we were able to take samples during the day of competition and the post-competitive days. Hormone levels were assayed with a routine in-house radioimmunoassay (RIA) method. Throughout the competition, C levels increased sharply (about 2.5-fold compared resting values) and returned to basal values within 4 h. Conversely, the T level decreased slightly. During the recovery period, C levels were lower and T levels were higher than basal values, resulting in a very high T/C ratio until the 5th day. This high post-competitive T/C ratio phase is probably required to restore the break-down of homeostasis induced by the very hard mental and physical strain associated with a rugby match. Thus, a period of 1 week recovery appears to be the minimal duration between two competitions.

Adaptation, Physiological↗