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Biomedical subjects

M Lessard

Publications and source records attributed to M Lessard.

At least 37 records · Page 2Linked to original sources
PubMed2002

High incidence of Hox11L2 expression in children with T-ALL.

The orphan homeobox gene HOX11L2 was previously found to be transcriptionally activated as a result of the t(5;14)(q35;q32) translocation in three T-ALL cases. We now tested by RT-PCR Hox11L2 expression in 23 consecutive cases of T-ALL (15 children aged 0.8-14 years, eight adults aged 17-55 years) and as control 13 B-ALL patients from a single institution. Hox11L2 expression was undetectable in all patients with B-ALL, nor in adults with T-ALL. Nine children (60% of the cases), all boys, expressed Hox11L2. Blast cells from most of the latter patients carried surface CD1a, CD10 and not CD34 antigens, in contrast to the other children. FISH, M-FISH and IPM-FISH analysis failed to detect a t(5;14)(q35;q32) in one of them, which suggests a possible distinct genetic mechanism in Hox11L2 expression induction. Hence, Hox11L2 expression seems to be the most frequent abnormality in childhood T-ALL to date, comparable to the t(12;21) in child B-ALL.

Adolescent↗
PubMed2001

Behavioural responses of piglets to castration: the effect of piglet age.

It has long been assumed that neonatal animals are less sensitive than older animals to pain, and this reasoning has been used to recommend that routine surgical procedures be performed at an early age. In this study we tested if vocal and other behavioural responses to castration increase with piglet age. Piglets (n=84) from 14 litters were assigned to one of six treatment groups: castration or sham castration at 3, 10 or 17 days of age. During the procedure castrated piglets produced high-frequency calls (>1000Hz) at more than three times the rate of piglets in the sham-castrate group. The rate of low-frequency (<1000Hz) calls was also higher for piglets in the castrate group. The rate of high-frequency calling was lower for the youngest pigs but there was no relationship between age and the effect of treatment for any of the vocal responses measured (i.e. no age by treatment interaction). During the first 2h after castration, castrated piglets spent more time sitting or standing and less time lying. During the subsequent 22h, castrated piglets spent marginally more time at the udder and less time lying down. Older piglets missed more nursings. However, the effect of castration did not vary with the age of the piglet for any measure. We conclude that while the factors affecting both the shams and the castrates (e.g. distress due to restraint) may vary with age, the pain of castration is not affected by age within the range of ages that we tested.

Journal Article↗
PubMed2001

A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia.

FISH identified a cryptic t(5;14)(q35;q32) in T acute lymphoblastic leukemia (ALL), whereas it was not observed in B ALL samples. This translocation is present in five out of 23 (22%) children and adolescents with T ALL tested. RanBP17, a gene coding for a member of the importin beta protein family, and Hox11Like2, an orphan homeobox gene were mapped close to the chromosome 5 breakpoints and CTIP2, which is highly expressed during normal T cell differentiation, was localized in the vicinity of the chromosome 14 breakpoints. The Hox11L2 gene was found to be transcriptionally activated as a result of the translocation, probably under the influence of CTIP2 transcriptional regulation elements. These data establish the t(5;14)(q35;q32) as a major abnormality, and Hox11 family member activation as an important pathway in T ALL leukemogenesis.

Adolescent↗
PubMed2000

Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Groupe Français de Cytogénétique Hématologique, Groupe de Français d'Hematologie Cellulaire, UK Cancer Cytogenetics Group and BIOMED 1 European Community-Concerted Action "Molecular Cytogenetic Diagnosis in Haematological Malignancies".

Acute promyelocytic leukemia (APL) is typified by the t(15;17), generating the PML-RAR alpha fusion and predicting a beneficial response to retinoids. However, a sizeable minority of APL cases lack the classic t(15;17), prompting the establishment of the European Working Party to further characterize this group. Such cases were referred to a workshop held in Monza, Italy and subjected to morphologic, cytogenetic, and molecular review, yielding 60 evaluable patients. In the majority (42 of 60), molecular analyses revealed underlying PML/RAR alpha rearrangements due to insertions (28 of 42) or more complex mechanisms, including 3-way and simple variant translocations (14 of 42). Metaphase fluorescence in situ hybridization (FISH) demonstrated that insertions most commonly led to formation of the PML-RAR alpha fusion gene on 15q. In 11 of 60 workshop patients, PLZF/RAR alpha rearrangements were identified, including 2 patients lacking the t(11;17)(q23;q21). In one case with a normal karyotype, FISH analysis revealed insertion of RAR alpha into 11q23, and PLZF-RAR alpha was the sole fusion gene formed. Two patients were found to have t(5;17), one with a diffuse nuclear NPM staining pattern and with NPM-RAR alpha and RAR alpha-NPM transcripts detected. In the other with an unbalanced der(5)t(5;17)(q13;q21) and a nucleolar NPM localization pattern, an NPM/RAR alpha rearrangement was excluded, and FISH revealed deletion of one RAR alpha allele. In the remaining 5 workshop patients, no evidence was found for a rearrangement of RAR alpha, indicating that in rare instances, alternative mechanisms could mediate the differentiation block that typifies this disease. This study highlights the importance of combining morphologic, cytogenetic, and molecular analyses for optimal management of APL patients and better understanding of the pathogenesis of the disease. (Blood. 2000;96:1297-1308)

Adult↗
PubMed2000

Reference values for differences between cardio-circulatory variables of normal twin fetuses.

BACKGROUND: No reference values exist concerning the differences between cardio-circulatory variables of normal twin fetuses. The normal data could be useful in the identification of conditions causing opposite hemodynamic effects on each twin. OBJECTIVE: To establish the normal differences among cardio-circulatory parameters of twin fetuses during the second and third trimesters of gestation. MATERIALS AND METHODS: Twenty-seven normal twin pregnancies were used in this longitudinal and prospective study. Doppler-echocardiographic investigations were performed every 2-3 weeks starting at an average of 23.11 +/- 3.13 (mean +/- standard deviation) weeks' gestation. At each visit, the following cardio-circulatory variables were evaluated: the cardio-thoracic ratio, the ventricular wall and septal thicknesses, end-diastolic and systolic diameters, ventricular fractional shortenings, velocity of circumferential fibre shortenings and left and right ventricular outputs. In addition the following measurements were made from Doppler recordings: through both aortic and pulmonary valve the acceleration and ejection times, the peak systolic velocities and the velocity time integrals; and through both mitral and tricuspid valves peak velocities of E and A waves and the E/A ratios. Finally the pulsatility index of the umbilical artery was also evaluated. RESULTS: There was no single variable where the intertwin difference changed with gestational age. No systematic difference between the smaller and larger twin could be demonstrated for any variables except for the cardio-thoracic ratio. CONCLUSION: Reference tables should permit a comparative approach between the two twins in the investigation of life threatening complications such as twin-to-twin transfusion syndrome.

Blood Flow Velocity↗
PubMed2000

Pancreatic inflammation, apoptosis, and growth: sequential events after partial pancreatectomy in pigs.

Positive signs of pancreas regeneration were observed in rats after induced pancreatitis and partial pancreatectomy (1,2). Although the human pancreas did not regenerate after partial anatomic resection (3), the pig pancreas exhibited growth responses to bombesin after partial pancreatectomy (4). This study was undertaken to establish the time course of pancreatic inflammation, apoptosis, and hypertrophy and/or hyperplasia after partial pancreatectomy in pigs.

Animals↗
PubMed2000

Correlation between electrocardiographic and ultrasonographic time-interval measurements in fetal lamb heart.

The objective of this study was to establish the echocardiographic modality that best correlates with electrical events in the fetal heart. No documentation on the relationship between electrical events recorded with a surface ECG and fetal M-mode or Doppler echocardiographic measurements is available. The following ultrasound tracings were recorded simultaneously with a surface ECG on six exteriorized near-term fetal lambs: 1) M-mode echocardiography of atrial and ventricular contractions; and 2) Doppler flow velocity waveforms in the right superior vena cava (SVC) either alone or 3) in association with those of the ascending aorta. In the SVC, the onset of the retrograde A wave and the beginning of the forward wave during ventricular systole were used as markers for the start of the P wave and QRS complex, respectively. For the simultaneous SVC and ascending aorta tracings, the beginnings of the A and of the aortic ejection waves were used as markers. On average, the atrioventricular interval was 84 ms longer than the PR interval with the M-mode, corresponding to an increase of 107%. A similar observation was made for the simultaneous Doppler signals from SVC and ascending aorta, but the difference between the atrioventricular and PR intervals was smaller, averaging 35 ms. When the SVC Doppler was taken alone, no significant difference was found between atrioventricular and ventriculoatrial compared with PR and RP intervals, respectively, and a strong correlation was found between the two methods of measurement, both for the atrioventricular (r = 0.91) and ventriculoatrial (r = 0.89) intervals. Doppler interrogation of the SVC alone and, to a lesser degree, of the SVC and ascending aorta are reliable indirect markers for the timing of electrical events of the fetal lamb heart in sinus rhythm.

Animals↗
PubMed1999

Relationship between flow through the fetal aortic isthmus and cerebral oxygenation during acute placental circulatory insufficiency in ovine fetuses.

OBJECTIVE: We sought to investigate whether the reversal of blood flow through the aortic isthmus, as observed during an increase in placental vascular resistance, could be responsible for a significant fall in oxygen delivered to the fetal brain. STUDY DESIGN: With the appearance of reverse flow in the aortic isthmus, preplacental blood with low oxygen saturation could contaminate the ascending aorta blood destined for the brain. Stepwise compression of the umbilical veins of 8 exteriorized fetal lambs was realized at approximately 140 days of gestation. Four other animals were used as controls. Flows through the aortic isthmus and both carotid and umbilical arteries were measured by Doppler echocardiography in the basal state (hemodynamic class 1) and during moderate (class 2), severe (class 3), and extreme (class 4) increases in resistance to placental flow. Oxygen delivered to the brain was calculated from carotid blood flow and oxygen content. RESULTS: In the control group no change was noted in umbilical and carotid arteries or in the aortic isthmus blood flow. Oxygen delivered to the brain remained stable. In the study group the increase in resistance to placental flow caused a significant fall in umbilical flow and carotid oxygen content, while blood flow in the carotid arteries increased slightly. The values for aortic isthmus flow and oxygen delivered to the brain during the 4 hemodynamic classes were, on average, as follows: class 1, 98.2 and 2.9 mL/(min x kg); class 2, 52.8 and 3.1 mL/(min x kg); class 3, 3.7 and 2.6 mL/(min x kg); and class 4, -29.8 and 0.7 mL/(min x kg), respectively. CONCLUSION: During an acute increase in placental vascular resistance, delivery of oxygen to the brain is preserved despite a significant drop in arterial oxygen content as long as net flow through the isthmus is anterograde.

Acidosis↗
PubMed1998

FISH investigation of 5q and 7q deletions in MDS/AML reveals hidden translocations, insertions and fragmentations of the same chromosomes.

We have studied, by fluorescence in situ hydridization (FISH), chromosomes 5 and 7 in a series of 11 cases with 5q deletion, as sole anomaly (four cases), or in association with 7q deletion (seven cases), in MDS/AML patients. We found that, in some cases, a part of the so-called 'lost' chromosome 5 and 7 material, was actually translocated. These translocations may be either end-arm or whole-arm, as well as small insertions. Chromosomes 5 or 7 may be broken in more than two segments, defining 'fragmentation', giving rise to marker chromosomes. FISH allowed the identification of small material insertion, which is totally unidentified by classical cytogenetics. Chromosome 5 and 7 translocations occur irrespectively of the 'de novo' or 'secondary' type of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) patients.

Acute Disease↗
PubMed1998

Extramedullary relapse after favorable molecular response to donor leukocyte infusions for recurring acute leukemia.

Donor leukocyte infusions (DLI) have turned out to be an efficient way to re-establish complete remission (CR) in chronic myeloid leukemia (CML) patients relapsing after allogeneic bone marrow transplantation (BMT). In these patients, absence of PCR bcr-abl fusion transcripts confirmed the potency of donor leukocytes to induce molecular response in relapsed CML. This ensured sustained remission and long-term survival. In this study, the capacity of DLI to induce molecular remission in acute leukemia relapse after BMT was analyzed. The results showed that following DLI, leukemic cell eradication gradually occurred over a prolonged time period. The time to complete disappearance of the molecular marker of the disease was 30 weeks in RT-PCR analysis. A sustained and persistent elimination of an AML1/ETO-positive leukemic clone in an AML-M2 patient was observed. In contrast, an AML-M5 with t(11;19) and an E2A/PBX1-positive ALL achieving cytogenetic and molecular bone marrow CR developed following DLI unusual sites of extramedullary leukemia relapse, despite continued bone marrow remission. This study adds further proof of the benefit of donor cell therapy in acute leukemia but shows that complete leukemic cell eradication appears to require a critical interval in order to establish effective immune responses at all sites where leukemic cells persist.

Adult↗
PubMed1998

A quantitative competitive reverse transcription-polymerase chain reaction technique to measure porcine interferon-gamma.

In swine, as in other mammals, interferon-gamma (IFN-gamma) plays an important role in the regulation of the immune response. The objective of this work was to develop a sensitive, quantitative competitive reverse transcription-polymerase chain reaction (qcRT-PCR) assay, using an internal cRNA standard, to monitor the expression of porcine IFN-gamma gene. We applied this qcRT-PCR assay to quantify the expression of IFN-gamma transcripts in peripheral blood mononuclear cells (PBMC) incubated for different times with or without concanavalin A (ConA). Results showed that the expression of the IFN-gamma transcripts in PBMC occurred within the first 2 h after mitogenic stimulation and reached a peak after 24 h of incubation with ConA. The qcRT-PCR technique provides an efficient and sensitive tool for studying the expression of porcine IFN-gamma gene under a variety of experimental conditions. This will help to understand the regulation of T cell-mediated immune responses by IFN-gamma at the gene level.

Animals↗
PubMed1997

A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.

The Janus family of tyrosine kinases (JAK) plays an essential role in development and in coupling cytokine receptors to downstream intracellular signaling events. A t(9;12)(p24;p13) chromosomal translocation in a T cell childhood acute lymphoblastic leukemia patient was characterized and shown to fuse the 3' portion of JAK2 to the 5' region of TEL, a gene encoding a member of the ETS transcription factor family. The TEL-JAK2 fusion protein includes the catalytic domain of JAK2 and the TEL-specific oligomerization domain. TEL-induced oligomerization of TEL-JAK2 resulted in the constitutive activation of its tyrosine kinase activity and conferred cytokine-independent proliferation to the interleukin-3-dependent Ba/F3 hematopoietic cell line.

Amino Acid Sequence↗
PubMed1997

Doppler velocimetric indices from the abdominal and placental ends of the umbilical artery of growth-restricted fetuses.

PURPOSE: In normal pregnancies, as gestation advances, a progressive decrease is observed in the differences between Doppler indices recorded at the 2 extremities of the umbilical cord. The purpose of this study was to determine whether the same pattern is observed in pregnancies complicated by intrauterine growth restriction (IUGR). METHODS: Forty-seven fetuses with sonographic diagnosis of IUGR underwent investigation by Doppler sonography. Blood flow velocities were measured at the abdominal and placental ends of the umbilical cord. The systolic-diastolic ratio, pulsatility index, and resistance index were calculated for each site. The differences in values between the 2 ends of the cord were calculated (abdominal end minus placental end) and then compared with the differences calculated for normal fetuses. RESULTS: In contrast to normal fetuses, IUGR fetuses with abnormal Doppler measurements had significant differences in the pulsatility and resistance indices between the 2 ends of the cord after 28 weeks of gestation. In addition, when compared with normal fetuses, the IUGR fetuses had a significantly greater difference in the values for the 2 ends of the cord for all indices. CONCLUSIONS: These results emphasize the importance of identifying the sampling site for serial Doppler investigations in IUGR-complicated pregnancies.

Abdomen↗
PubMed1997

Chromosome abnormalities of the short arm of chromosome 12 in hematopoietic malignancies: a report including three novel translocations involving the TEL/ETV6 gene.

A wide variety of abnormalities of the short arm of chromosome 12 has been reported in hematologic malignancies. The most frequent rearrangements result from t(12;21)(p13;q22) of childhood acute lymphoblastic leukemia, a translocation cryptic when leukemic cells are analyzed with chromosome banding techniques. This translocation results in a fusion of the TEL/ETV6 and AML1 genes. In this report, examples of rearrangements of 12p are presented. Study of two complex chromosome abnormalities associated with t(12;21) emphasizes the importance of using FISH in detection of such translocations. Three novel translocations involving the TEL/ETV6 gene localized on 12p13 are also reported: t(X;12)(q28;p13), t(1;12)(q21;p13), and t(9;12)(p23-24;p13). Finally, the presentation of two translocations with breakpoints located centromeric to TEL/ETV6 highlights the not uncommon involvement of genes other than TEL/ETV6 on 12p.

Adolescent↗
PubMed1997

Cell-mediated and humoral immune responses in broiler chickens maintained on diets containing different levels of vitamin A.

Broiler chickens were examined for the effects of low (400 IU/kg), standard (1,500 IU/kg), or high (15,000 IU/kg) dietary vitamin A (VitA) levels on immune responsiveness postimmunization to Newcastle disease virus (NDV). A control pair-fed group (1,500 IU/kg) was included to compensate for the reduced feed intake associated with diet containing the low level of VitA. Interdigital skin reactions to phytohemagglutinin (PHA) and CD4:CD8 T lymphocyte ratios were significantly reduced in chickens fed the low VitA diet, whereas their antibody responses to NDV were significantly increased as compared to birds that consumed the 1,500 to 15,000 VitA diet ad libitum. On the other hand, birds on the high VitA diet had reduced lymphocyte responses to concanavalin A and pokeweed, but not to PHA. No effect of dietary VitA was observed for natural killer activity, nor on levels of percentage of cells expressing Class II MHC antigens among groups that consumed feed ad libitum. The results indicated that both humoral and cellular immune responses were modulated by levels of VitA in the diet, and suggest that VitA-deficient chickens developed a T helper (Th)2 immune response, whereas the chickens fed highly enriched VitA diet showed a Th1 immune response.

Animals↗
PubMed1997

Chromosome 8 tetrasomies and pentasomies--a clonal abnormality closely associated with acute monocytic leukaemia.

We report four cases of polysomy 8 (one tetrasomy and three pentasomies) observed in acute monocytic leukemia (FAB M4 and M5). Three of them showed a rearrangement of 11q23 identified by conventional cytogenetic analysis and/or chromosome painting. Our cases as well as a review of the literature, suggest that polysomy 8 is preferentially associated with monocytic differentiation (24/31). These polysomies have been observed in 21 de novo leukemias and in 10 secondary hematological disorders. A 11q23 rearrangement has been detected in 9 out of 32 patients, by conventional cytogenetic techniques in 7 and by FISH in 2. We suggest that these cases should be analysed by FISH and molecular studies in order to detect a rearrangement of MLL/11q23. Monocytic differentiation is often associated with a change of the MLL gene and the polysomy 8 might be a particular clonal evolution secondary to 11q23 abnormality.

Adolescent↗
PubMed1996

[Importance of intrauterine diagnosis of rudimentary autonomic circulation in an acardiac twin].

Foetal acardia is a major complication of twin pregnancies which endangers the life of the healthy twin. The authors report the case of a twin pregnancy with an acardiac twin followed up by repeated echocardiography from the 20th week of pregnancy until delivery at the 36th week. Despite the presence of a parasitic mass, the healthy twin showed no sign of heart failure. Attentive ultrasonography of this mass showed a certain degree of autonomic circulation ensured by a rudimentary cardiac pump. This case confirms the favorable effect of this finding on the healthy twin, moreover, it clarifies some haemodynamic features of the parasitic mass: to-and-fro circulation, characteristic of a cardiac pump without a valve, anastomoses and competitive flow between the two circulatory systems.

Abnormalities, Multiple↗