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M Lessard

Publications and source records attributed to M Lessard.

At least 19 recordsLinked to original sources
PubMed2006

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique.

Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.

Adolescent↗
PubMed2006

[A cytological, immunophenotypical and cytogenetical study of 136 consecutive cases of B-cell chronic lymphoid hemopathies].

A cytological, immunophenotypical and cytogenetical study of 136 chronic B-cell proliferations (93 CLL, 43 B-cell lymphomas) was led in order to precise diagnosis and to characterize and appreciate chromosomal rearrangements. In this series, mainly selected on blood lymphocytosis criteria, B-CLL were twice more frequent than small B-cell lymphomas. Probes used revealed cryptic abnormalities, which remained unknown by conventional cytogenetics (CC). The frequency of clonal abnormalities (CC and FISH) was 74.8% for this series, with 74.4% for lymphomas and 75.3% for CLL, mainly of Binet stage A (69 A, 13 B, 1 C, 10 unspecified). Proportion was 88.4% in A stages and 84.6% in B stages. In CLL, 13q14 cryptic deletions and translocations were widely majority, 14q32 translocations and trisomy 12 being predominant in lymphoma series. Interphase FISH study of non-clonal metaphasic abnormalities with locus-specific probes often revealed unrecognised clones.

Aneuploidy↗
PubMed2006

Circulating procoagulant microparticles in obesity.

AIM: Obesity is a risk factor for cardiovascular diseases and venous thromboembolism. Circulating procoagulant microparticles (MP) have been described in various clinical situations associated with thrombosis and in diabetic patients. The aim of this preliminary study was to evaluate the presence of MP in obese patients without any other vascular risk factor in particular diabetes. METHODS: Fifty-eight obese women <50 year-old without other cardiovascular risk factors were recruited from a single out-patient nutrition clinic. They were compared to 45 age-matched healthy normal weight controls. Main outcome was MP levels in patients and controls. Relationships between MP concentrations and parameters reflecting insulin resistance in patients were also studied. RESULTS: Obese patients were 33.3 +/- 1.2 years old and had a mean BMI of 42.4 +/- 0.9 kg/m2. There vas a greater proportion of smokers in the obese group (34.5 vs 15.6%). Mean MP levels were markedly higher in obese patients compared to controls (10.6 +/- 0.5 vs 3.2 +/- 0.3 nMPSeq, P < 0.001). There was no difference in MP concentrations between smokers and non smokers. In the obese group, there was a negative correlation between MP and BMI (r = -0.265, P < 0.05) but no relationship could be established between MP concentrations and markers of insulin resistance. CONCLUSION: This increase in circulating MP levels reflects cell activation and could account for the increased risk of thrombotic complications in obesity. Further studies are ongoing to explore the relationships between MP levels and coagulation markers and to assess the effect of weight reduction.

Adult↗
PubMed2006

Loss of the NPM1 gene in myeloid disorders with chromosome 5 rearrangements.

The assignment with chromosome banding techniques of the breakpoints of the recurrent translocation t(3;5) which leads to NPM1/MLF1 gene fusion in myeloid malignancies has not been unequivocal. In order to assess whether this is due to uncertainty in interpretation of the observed banding pattern or whether it reflects true genomic heterogeneity, we decided to analyze the breakpoint positions using fluorescence in situ (FISH) techniques in eight patients with myeloid malignancies and rearrangements of chromosomes 3 and 5. In three patients, colocalization of the NPM1 and MLF1 spanning BACs was demonstrated and NPM1/MLF1 fusion shown by PCR in one while in the remaining cases breakpoints were located outside the NPM1 and MLF1 loci. Interestingly, loss of a copy of the NPM1 gene was found in three of these latter patients. This findings suggest that haploinsufficiency of NPM1 may play a role in subtypes of myelodysplasias and leukemias.

Adult↗
PubMed2006

Effect of postruminal glutamine supplementation on immune response and milk production in dairy cows.

Seventeen multiparous Holstein cows were used to examine the effect of an increased duodenal supply of Gln on immune function and production. Cows received continuous abomasal infusions of water (control: n = 8) or 300 g/d of Gln (n = 9) for 21 d starting within 48 h of calving. There were nonsignificant increases in milk and milk protein yields in response to Gln supplementation. Glutamine treatment had no effect on plasma glucose, nonesterified fatty acids (NEFA), or beta-hydroxybutyrate (BHBA) concentrations but did tend to increase plasma urea N concentration. The Gln treatment resulted in an increase of 108 microM in the plasma Gln concentration. Total essential AA concentrations decreased with the Gln treatment, whereas total nonessential AA concentrations were unaffected. T Lymphocyte proliferation did not differ between the control and Gln-treated cows. Treatment had no effect on the relative abundance of CD8 T cells but did increase the abundance of CD4 T cells. Cytokine production, as measured by IFN-gamma concentration determined in vitro in concanavalin-A-stimulated peripheral blood mononuclear cells, was similar between the treatments. Over the first 3 wk following calving, Gln supplementation had limited effects on milk production, metabolic parameters, and immune function.

3-Hydroxybutyric Acid↗
PubMed2005

Cytogenetic study of 75 erythroleukemias.

Chromosomal abnormalities of erythroleukemia (EL) are often described as complex and unspecific. A retrospective study of 75 EL defined following the WHO classification was performed by the Groupe Francophone de Cytogénétique Hématologique (GFCH) in order to reexamine the cytogenetics of this infrequent leukemia subtype. Clonal chromosomal abnormalities were found in 57 patients (76%), distributed in 4 subgroups according to their ploidy status: pseudodiploid (16%), hypodiploid (47%), hyperdiploid (19%), and 18% mixed cases associating 2 different clones (hypodiploid+hyperdiploid) or (pseudodiploid+hyperdiploid). Complex rearrangements and hypodiploid chromosome number were widely dominant (50%). Partial or entire monosomies represented 56% of abnormalities. Chromosomes 5 and 7 were the most frequently involved (41 and 33 times, respectively), followed by chromosomes 8, 16, and 21 (19 times each). Unbalanced abnormalities were more frequent than balanced. All these kinds of abnormalities were observed in de novo as well as in secondary EL. Four out of 7 cases of "pure erythroid" leukemia were associated with a BCR-ABL fusion. Lastly, no chromosome abnormality specific to EL could be established. However, the large overlap of chromosomal abnormality patterns of EL (pure erythroid form excepted) and refractory anemia with excess of blasts in transformation (RAEB-t) favors the hypothesis of similarities between these 2 hematologic disorders.

Adolescent↗
PubMed2005

Latent acute promyelocytic leukemia t(15;17)(q22;q12-21) and sarcoidosis: long-term cohabitation.

The association of sarcoidosis with hematological malignancies is a well-known phenomenon. To our knowledge, we report the first case involving sarcoidosis and acute promyelocytic leukemia (APL) t(15;17)(q22;q12-21). The major interest lies in the chronology of the two diseases: the APL demonstrated an unusual smoldering evolution, suggesting that pre-existing sarcoidosis may have a non-fortuitous immunological impact on leukemic clone proliferation.

Journal Article↗
PubMed2004

Effect of oestrous cycle and early pregnancy on uterine production and expression of immune regulatory factors in gilts.

This study was undertaken to characterize uterine immune factors involved in the establishment of pregnancy in gilts. Thirty crossbred Yorkshire-Landrace gilts of similar age and weight were observed twice a day for oestrous behaviour with intact boars. On the day of first standing oestrus (Day 0) and 12h later, 15 gilts were inseminated with pooled semen from Duroc boars of proven fertility. Pregnant gilts were slaughtered either on Days 10, 15 or 25 of gestation (n=5 per day). The other 15 gilts were not inseminated and were slaughtered on either Days 0, 10 or 15 of the oestrous cycle (n=5 per day). Immediately after slaughter, endometrial tissue samples from the mesometrial side were removed for gene expression using RNase protection assay and in situ hybridization methodologies. The other uterine horn was flushed with 20 ml of PBS to collect the uterine fluid. In pregnant gilts, endometrial interleukin (IL)-6 mRNA expression was higher on Day 15 than on Days 10 and 25 (P<0.01 and P<0.1, respectively). On Day 15, IL-6 expression was also significantly higher (P<0.01) in pregnant gilts than in cyclic gilts. In both pregnant and cyclic gilts, transforming growth factor (TGF)-beta2 in uterine fluid was significantly higher (P<0.0001) on Day 15 than on Day 10. At the gene expression level, TGF-beta2 also increased between Days 10 and 15 in both cyclic and pregnant gilts but differences were not significant. On Day 15, concentrations of interferon-gamma and prostaglandin E(2) (PGE(2)) in uterine fluid were markedly higher (P<0.001) in pregnant gilts than in cyclic gilts, whereas the total amount of TGF-beta2 in uterine fluid and its endometrial expression were approximately 70% higher although this increase was not significant. Finally, tumour-necrosis factor-alpha and granulocyte-macrophage/colony-stimulating factor mRNA expressions were undetectable in all endometrial samples. In conclusion, production and/or expression of uterine TGF-beta2, IL-6 and PGE(2) increased during the embryonic attachment period and are coincidental with embryonic interferon-gamma production.

Animals↗
PubMed2004

Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemia.

Imatinib mesylate (Gleevec), an inhibitor of the BCR-ABL tyrosine kinase, was introduced recently into the therapy of chronic myeloid leukemia (CML). Several cases of emergence of clonal chromosomal abnormalities after therapy with imatinib have been reported, but their incidence, etiology and prognosis remain to be clarified. We report here a large series of 34 CML patients treated with imatinib who developed Philadelphia (Ph)-negative clones. Among 1001 patients with Ph-positive CML treated with imatinib, 34 (3.4%) developed clonal chromosomal abnormalities in Ph-negative cells. Three patients were treated with imatinib up-front. The most common cytogenetic abnormalities were trisomy 8 and monosomy 7 in twelve and seven patients, respectively. In 15 patients, fluorescent in situ hybridization with specific probes was performed in materials archived before the initiation of imatinib. The Ph-negative clone was related to previous therapy in three patients, and represented a minor pre-existing clone that expanded after the eradication of Ph-positive cells with imatinib in two others. However, in 11 patients, the new clonal chromosomal abnormalities were not detected and imatinib may have had a direct effect. No myelodysplasia was found in our cohort. With a median follow-up of 24 months, one patient showed CML acceleration and two relapsed.

Adult↗
PubMed2004

Influence of parturition and diets enriched in n-3 or n-6 polyunsaturated fatty acids on immune response of dairy cows during the transition period.

The objectives of this study were to evaluate the functional properties of immunocompetent cells in dairy cows fed diets enriched in n-3 or n-6 polyunsaturated fatty acids during the transition period. Six weeks before calving, 21 primiparous and 27 multiparous pregnant Holstein dairy cows were randomly allotted to 1 of 3 dietary fat treatments: calcium salts of palm oil (Megalac), micronized soybeans, or whole flaxseed, which are, respectively, rich in saturated, n-6, or n-3 fatty acids. On wk 6 and 3 before parturition, cows received a subcutaneous injection of ovalbumin to measure the antibody response in colostrum and serum. Colostrum samples were collected at the first milking after calving, and blood samples were taken 6, 3, and 1 wk before the expected calving date and 1, 3, and 6 wk after calving. Blood mononuclear cells were cultured to evaluate the proliferative response to concanavalin A and the in vitro productions of interferon-gamma, tumor necrosis factor-alpha, nitric oxide, and prostaglandin E2. The serum antibody response to ovalbumin was unaffected by dietary fatty acids, but the response was lower in primiparous cows than in multiparous cows. A significant diet x parity interaction indicated that colostral antibody level against ovalbumin was significantly higher in multiparous cows fed soybeans than in those fed flaxseed or Megalac; there was no difference among treatments for primiparous cows. The lymphocyte response to concanavalin A was lower in cows fed soybeans than in those receiving flaxseed or Megalac when the cells were incubated with autologous serum. The proliferative response of mononuclear cells incubated with autologous serum was suppressed in the 1st wk after calving in both primiparous and multiparous cows, and multiparous cows showed a higher response than primiparous cows throughout the experiment. There was a significant interaction between parity and diet as a result of a greater production of interferon-gamma by mononuclear cells incubated with autologous serum in multiparous cows than in primiparous cows fed flaxseed; there was no difference among cows fed the other diets. Interferon-gamma production was reduced around calving while the inverse was observed for productions of nitric oxide and tumor necrosis factor-alpha. Productions of nitric oxide, prostaglandin E2, and tumor necrosis factor-gamma were greater in primiparous cows than in multiparous cows. In conclusion, functional properties of lymphocytes and monocyte/macrophage lineage of dairy cows during the transition period are modulated by parturition and the composition of polyunsaturated fatty acids in the diet.

Animals↗
PubMed2003

[Chromosomal abnormalities in secondary myelodysplastic syndromes and leukemias].

Secondary leukemias group essentially together myelodysplastic syndromes and acute leukemias, therapy-related (chemo- or radio-), or consecutive to environmental factors. It's now proven that some recurrent abnormalities are associated with effects of therapeutic agents, as -5/del(5q), -7/del(7q) linked to alkylating agents, or 11q23 and 21q22 abnormalities linked to inhibitors of Topoisomerase II. Even if important differences between secondary and "de novo" forms exist, the discrimination between these 2 categories is not always obvious: many common chromosomal abnormalities, "de novo" leukemias in older patients having characteristics close to those of postalkylating leukemias, neonatal forms possibly secondary to maternal affect. Recent studies identified some others chromosomal abnormalities in the secondary leukemias and confirmed the poor prognosis of these hemopathies. This review sums up criterions, circumstances and cytogenetic abnormalities.

Antineoplastic Agents, Alkylating↗
PubMed2003

Modification of topoisomerase genes copy number in newly diagnosed childhood acute lymphoblastic leukemia.

Topoisomerase genes were analyzed at both DNA and RNA levels in 25 cases of newly diagnosed childhood acute lymphoblastic leukemia (ALL). The results of molecular analysis were compared to risk group classification of children in order to identify molecular characteristics associated with response to therapy. At diagnosis, allelic imbalance at topo-isomerase IIalpha (TOP2A) gene locus was found in 75% of informative cases whereas topoisomerase I and IIbeta gene loci are altered in none or only one case, respectively. By semi-quantitative Polymerase chain reaction, we found a 2.5 to 8-fold TOP2A gene amplification in 72% of the children, which was correlated to gene overexpression in every case. These results show that TOP2A gene amplification is a frequent event in ALL at diagnosis. Interestingly, we also identified a small population of children that do not present TOP2A gene amplification or gene overexpression and who are significantly associated with very high risk classified patients showing glucocorticoid resistance. In conclusion, characterization of TOP2A gene status in childhood ALL at diagnosis provides useful complementary information for risk assessment.

Adolescent↗
PubMed2003

Uterine immune reaction and reproductive performance of sows inseminated with extended semen and infused with pooled whole dead semen.

The objective of this study was to investigate the effect of infusing whole dead semen (WDS) after AI with diluted commercial semen on uterine inflammatory reaction and embryonic survival rate in gilts. Sixty Yorkshire-Landrace gilts were assigned at their second estrus to one of the following AI treatments: 1) commercial semen adjusted to 1 x 10(9) sperm cells (S1) per dose, followed by an infusion of 80 mL of WDS (S1-WDS); 2) S1 followed by an infusion of 80 mL of Beltsville Thawing Solution (S1-BTS); 3) commercial semen adjusted to 3 x 10(9) sperm cells (S3) per dose, followed by an infusion of 80 mL of BTS (S3-BTS); and 4) a negative control group, in which gilts received two infusions of 80 mL of BTS (BTS). Two days after the first AI, eight gilts from Groups 1, 2, and 4 were slaughtered and reproductive tracts were collected. One horn was cut open longitudinally along the antimesometrial aspect and endometrial samples were taken and immediately frozen for analysis of messenger RNA (mRNA) abundance for inflammatory cytokines and growth factors. The other horn was flushed with 20 mL of PBS, and the contents of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) were determined by ELISA. On d 25 after AI, gilts from Groups 1, 2, and 3 were slaughtered and their reproductive tracts were collected to evaluate the number of fetuses and corpora lutea. On d 2 after the first AI, only TGF-beta1 was detected in the flush of all gilts, and no difference was observed between S1-WDS, S1-BTS, and BTS gilts. Endometrial levels of IFN-gamma and interleukin (IL)-6 mRNA were marked in all gilts, but they were not affected by the AI treatments, whereas the mRNA abundances for IL-1 and IL-2 were negligible. Infusions of WDS or BTS after a fertile AI did not affect IGF-I, IGF-I receptor, or IGF-II mRNA levels compared with gilts infused with BTS only, whereas the mRNA abundance for the IGF-II receptor was decreased (P < 0.05) in WDS-infused gilts. In gilts inseminated with S1 doses, infusion of WDS did not affect the number of live embryos. Although infusions of WDS did not affect the mRNA level and secretion of the cytokines measured and did not improve embryonic survival rates, further studies are needed to better understand the influence of semen composition on the uterine response after mating.

Animals↗
PubMed2003

Effect of dietary fat sources on systemic and intrauterine synthesis of prostaglandins during early pregnancy in gilts.

The present experiment was conducted to determine the influence of dietary fatty acids C18:2n-6 and C18:3n-3 on the modulation of intrauterine synthesis of prostaglandin E2 (PGE2) and F2alpha (PGF2alpha) during early pregnancy in pigs. Prostaglandin E2 in uterine fluid has been previously reported to be associated with embryo survival and development. Thirty-two Yorkshire-Landrace nulliparous gilts were randomly allocated to four diets containing 5% supplemental fat. The four dietary treatments were: HT, hydrogenated tallow (26.5% C16:0 and 54.8% C18:0); SO, sunflower oil (61.3% C18:2n-6); LO, linseed oil (50.4% C18:3n-3); and SO(CLA), a mixture of sunflower oil and conjugated linoleic acids to provide 20% CLA. Treatments started 2 d after the first pubertal estrus (d -21) and lasted for 36 d (slaughter), which was 15 d after the second estrus (d 0; insemination). Fatty acids and PGE2 were measured in the peripheral blood plasma on d -19, d -7, d 0, and d 14. Fatty acids in endometrial tissues and PGE2 and PGF2alpha in the uterine fluid collected on d 15 were also measured. Concentrations of fatty acids in the plasma reflected the content of fatty acids in the diet as early as d -7. From d -7, PGE2 concentrations in the plasma were higher in gilts fed SO compared with HT (P < 0.05). Plasma PGE2 concentrations were lower (P < 0.01) on d 14 in gilts fed LO compared with HT. Total PGF2alpha contents in the uterine fluid of gilts fed LO were more than 70% lower (P < 0.05) than for the HT group. A similar trend was observed for total PGE2 content and for the ratio PGF2alpha:PGE2, but the effect (LO vs HT) was less marked (P < 0.07 and P < 0.10, respectively). There was no effect of SO or SO(CLA) on total PGE2 contents in the uterine fluid. Dietary enrichment in C18:2n-6 and/or C18:3n-3 for early pregnant gilts can influence fatty acids in plasma and endometrial tissue and can modulate circulatory and intrauterine prostaglandins.

Animal Feed↗
PubMed2003

Immune response of postpartum dairy cows fed flaxseed.

Thirty Holstein cows were allotted at calving to 10 groups of three cows blocked for similar calving dates to determine the effects of dietary fatty acids on functional properties of immunocompetent cells in early lactation and at breeding. Cows were assigned at calving to one of three isonitrogenous, isoenergetic, and isolipidic supplements based on either calcium salts of palm oil, Megalac, micronized soybeans, or whole flaxseed. On the day of AI and 20 d later, cows were injected with ovalbumin to measure the antibody response. Blood samples were taken at different times after calving (d 5, 21, 42, and 105) and after AI (d 0, 10, 20, and 40) for quantification of serum progesterone, fatty acids, and prostaglandin E2 concentrations. Isolated peripheral blood mononuclear cells were cultured to evaluate the proliferative response to concanavalin A and in vitro productions of interferon-gamma and prostaglandin E2. In general, feeding flaxseed increased serum omega-3 fatty acids concentration compared with feeding Megalac or soybeans, which decreased the omega-6 to omega-3 fatty acids ratio. There was a significant diet x day interaction for the proliferative response of mononuclear cells after calving and AI, indicating that cell responses from cows fed flaxseed were transiently reduced compared with those fed Megalac and soybeans. Moreover, during the breeding period, serum progesterone concentration was significantly greater in cows fed flaxseed compared with those fed Megalac, whereas serum concentration of prostaglandin E2 was significantly lower in cows fed flaxseed than in those fed Megalac or soybeans. Dietary treatments had no effect on the antibody response to ovalbumin and on in vitro productions of interferon-gamma and prostaglandin E2. However, interferon-gamma and prostaglandin E2 were impaired in the first 3 wk after parturition regardless of dietary treatment. These results suggest that changes in fatty acids, progesterone, and prostaglandins E2 concentrations in serum due to dietary treatment and physiological status influenced systemic immunity as shown by reduced proliferative response. However, other mechanisms must be considered and are discussed to explain dietary effect on lymphocyte proliferative response to mitogenic stimulation and other immune functions.

Animal Feed↗
PubMed2002

Translocation t(5;14)(q35;q32) in three cases of childhood T cell acute lymphoblastic leukemia: a new recurring and cryptic abnormality.

We report three cases of T-ALL in which conventional cytogenetic analysis yielded normal karyotypes, but for which a new M-FISH technique (IPM-FISH) was able to detect a translocation. For these patients this technique highlighted a new, recurring and cryptic translocation t(5;14)(q35;q32) in childhood T-ALL which might be phenotypically restricted. The most innovative part of this technique is the use of interspersed polymerase chain reaction (IRS-PCR) painting probes that show an R-band pattern simultaneous with the combinatorial labeling. Contrary to the DOP-PCR, IRS-PCR-derived probes provide stronger hybridization signals at the telomeric ends that potentially increase the possibility of detecting cryptic translocations. All the IPM-FISH findings were validated by FISH with whole chromosome painting and unique sequence probes. These results demonstrate the efficient use of IPM-FISH as an improved, single-step method for the identification of cryptic chromosomal abnormalities. This new IPM-FISH technique is a good tool to display cryptic chromosomal abnormalities.

Child↗