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Biomedical subjects

G Moreau

Publications and source records attributed to G Moreau.

At least 19 recordsLinked to original sources
PubMed1999

Increased fetal and extramedullary hematopoiesis in Fas-deficient C57BL/6-lpr/lpr mice.

In this study, we examined the consequences of Fas deficiency on hematopoiesis in C57BL/6-lpr/lpr mice. We found a striking extramedullary increase in hematopoietic progenitor cells, comprising erythroid and nonerythroid lineages alike. These modifications preceded the lymphadenopathy, because early progenitors (colony-forming units-spleen [CFU-S] day 8) were already augmented in day-18 fetal livers of the lpr phenotype. Three weeks after birth, CFU-S increased in peripheral blood and spleen and colony-forming cells (CFU-C) began to accumulate 1 to 3 weeks later. Extramedullary myelopoiesis augmented progressively in Fas-deficient mice, reaching a maximum within 6 months. By then, mature and immature myeloid cells had infiltrated the spleen, the liver, and the peritoneal cavity. Similar changes occurred in C57BL/6-gld/gld mice, indicating that they resulted from Fas/FasL interactions. Medullary hematopoiesis was not significantly modified in adult mice of either strain. Yet, the incidence of CFU-S decreased after Fas cross-linking on normal bone marrow cells in the presence of interferon gamma, consistent with a regulatory function of Fas/FasL interactions in early progenitor cell development. These data provide evidence that Fas deficiency can affect hematopoiesis both during adult and fetal life and that these modifications occur independently from other pathologies associated with the lpr phenotype.

Animals↗
PubMed1998

IL-4-producing NK T cells are biased towards IFN-gamma production by IL-12. Influence of the microenvironment on the functional capacities of NK T cells.

NK T cells are an unusual T lymphocyte subset capable of promptly producing several cytokines after stimulation, in particular IL-4, thus suggesting their influence in Th2 lineage commitment. In this study we demonstrate that, according to the cytokines present in the microenvironment, NK T lymphocytes can preferentially produce either IL-4 or IFN-gamma. In agreement with our previous reports showing that their IL-4-producing capacity is strikingly dependent on IL-7, CD4-CD8-TCRalphabeta+ NK T lymphocytes, obtained after expansion with IL-1 plus granulocyte-macrophage colony-stimulating factor, produced almost undetectable amounts of IL-4 or IFN-gamma in response to TCR/CD3 cross-linking. However, the capacity of these T cells to produce IFN-gamma is strikingly enhanced when IL-12 is added either during their expansion or the anti-CD3 stimulation, while IL-4 secretion is always absent. A similar effect of IL-12 on IFN-gamma production was observed when NK T lymphocytes were obtained after expansion with IL-7. It is noteworthy that whatever cytokines are used for their expansion, IL-12 stimulation, in the absence of TCR/CD3 cross-linking, promotes consistent IFN-gamma secretion by NK T cells without detectable IL-4 production. Experiments in vivo demonstrated a significant upregulation of the capacity of NK T cells to produce IFN-gamma after anti-CD3 mAb injection when mice were previously treated with IL-12. In conclusion, we provide evidence that the functional capacities of NK T cells, which ultimately will determine their physiological roles, are strikingly dependent on the cytokines present in their microenvironment.

Animals↗
PubMed1997

The management of spinal metastasis in children.

OBJECTIVE: To seek an optimal treatment plan from the results of treatment for metastatic disease of the spine in children. DESIGN: An 8-year retrospective study of children with metastatic disease of the spine. Imaging studies were reviewed and treatment modalities analysed. SETTING: The divisions of pediatric orthopedics and pediatric neurosurgery at the Children's Hospital of Eastern Ontario, Ottawa. PATIENTS: All children seen between April 1980 and December 1987 who had lesions metastatic to the spine by hematogenous or direct extension. There were 20 children (15 boys, 5 girls) with a mean age at the time of diagnosis of 9.5 years. Follow-up ranged from 2 weeks to 108 months. One child was lost to follow-up. INTERVENTIONS: Eleven children underwent laminectomy and decompression. Of the 14 neurologically compromised children, 5 received chemotherapy and radiotherapy and 9 received chemotherapy, radiotherapy and surgery. MAIN OUTCOME MEASURES: Type of metastatic lesion, vertebrae involved and response to therapy. RESULTS: Vertebrae involved with metastases were as follows: cervical (3), thoracic (5), lumbar (8) and multilevel (2). Meninges were involved in 2 cases. The most common causes of metastatic spinal involvement were neuroblastoma (4 cases) and astrocytoma (6 cases). Pathologic fractures occurred in 4 children and kyphoscoliosis in 4. Spinal cord paresis developed in 14 of the 20 children. Of the 6 children who survived from 48 to 108 months, 5 had tumours of neural origin, 4 being astrocytomas. Children with neuroblastoma or leukemic infiltration had a good initial response to chemotherapy. Five of the 6 surviving children had astrocytomas, and 5 were treated by surgical decompression. CONCLUSIONS: Metastatic disease of the spine in children secondary to astrocytoma should be treated aggressively, but from the experience gained from this study it is impossible to devise a rigid treatment plan for each type of metastatic tumour. The choice of chemotherapy, radiotherapy or surgery depends on the type of tumour, the age of the child and whether or not the spinal cord is compromised.

Adolescent↗
PubMed1997

[Diagnostic accuracy of teleradiology in thoracic and abdominal diseases].

For one year now, teleradiology has linked the "S. Marcello" Hospital to the Department of Radiology of "Del Ceppo." Hospital in Pistoia, 30 kilometers away. Plain films are digitized (Lumiscan 50, Philips), transmitted over a dedicated standard telephone line and displayed at 1024 x 1024 x 8 bits. To study the diagnostic accuracy of teleradiology in chest and abdominal conditions, we digitized and transmitted to the Pistoia Dept. of Radiology, a sample of 156 (96 chest and 60 abdominal) emergency examinations made in "S. Marcello" Hospital from January through November, 1995. The patients were 81 women (mean age: 69 years) and 75 men (mean age: 66 years); the age range was 17-93 years. Three radiologists independently reviewed the images in the Pistoia Dept. of Radiology on a digital workstation enabled to manipulate images. They filled in some given forms specific for chest and abdominal radiography, which were compared with the same forms filled in by the radiologist in "S. Marcello" Hospital who reviewed plain films. The differences were never clinically important; they concerned emphysema (4 false positives and 2 false negatives), congestion of the hila (2 false positives and 2 false negatives) and abnormal air in small bowel and colon (2 false positives and 2 false negatives). We believe these differences to be related to interobserver variability. The diagnostic accuracy of monitor image interpretation by the three radiologists who reviewed digitized radiographs exceeded 96% for both chest and abdominal examinations, which figure compares with literature data on high resolution workstations.

Adolescent↗
PubMed1996

Benign cartilage tumors.

Benign cartilaginous tumors are some of the most common lesions affecting the skeleton of children. These include exostoses, enchondromas, periosteal chondromas, chondromyxoid fibroma, and chondroblastoma. The clinicopathologic features of these conditions and their treatment is discussed.

Bone Neoplasms↗
PubMed1995

Surgical considerations in a diagnostic imaging evaluation of musculoskeletal masses.

The management of patients with soft-tissue masses necessitates careful assessment and appropriate use of investigational tools to obtain a diagnosis. The interaction among surgeons, radiologists, and pathologists allows adequate staging of soft-tissue tumors and better planning of the definitive treatment. The ability of MR imaging to maximize contrast between normal and tumor tissues in any desired plane makes it usually the best cross-sectional imaging modality in the preoperative staging of soft-tissue masses.

Bone Neoplasms↗
PubMed1994

Smooth muscle-specific switching of alpha-tropomyosin mutually exclusive exon selection by specific inhibition of the strong default exon.

Exons 2 and 3 of alpha-tropomyosin are spliced in a strict mutually exclusive manner. Exon 3 is a default choice, being selected in almost all cell types where the gene is expressed. The default selection arises from a competition between the two exons, in which the stronger branch point/pyrimidine tract elements of exon 3 win. Exon 2 is selected predominantly or exclusively only in smooth muscle cells. We show here that the basis for the smooth muscle-specific switching of exon selection is inhibition of exon 3. Exon 3 is still skipped with smooth muscle specificity, even in the absence of exon 2. We have defined two conserved sequence elements, one in each of the introns flanking exon 3, that are essential for this regulation. Mutation of either element severely impairs regulated suppression of exon 3. No other exon or intron sequences appear to be necessary for regulation. We have also demonstrated skipping of exon 3 that is dependent upon both regulatory elements in an in vitro splicing assay. We further show that both splice sites of exon 3 must be inhibited in a concerted fashion to switch to selection of exon 2. This may relate to the requirement for negative elements on both sides of the exon.

Alternative Splicing↗
PubMed1994

Val-237 for Ala substitution in the TEM-2 beta-lactamase dramatically alters the catalytic efficiencies towards carbenicillin and ticarcillin.

The mutant 554 of TEM-2 beta-lactamase was selected for a decrease in the resistance to carbenicillin of an Escherichia coli K12 carrier. The amino acid sequence of the mutant beta-lactamase was determined by manual Edman degradation analysis of proteolytic peptides. A single substitution Val for Ala was localized at position 237. The mutant exhibited only 2% of the catalytic efficiency of the wild-type enzyme towards carbenicillin and ticarcillin, whereas it retained 30-60% of the hydrolytic activity towards other penicillin and cephalosporin substrates. Carfecillin, the phenyl ester of the side-chain carboxyl group of carbenicillin, was hydrolysed as a good substrate. This suggests that the behaviour of the mutant enzyme towards carbenicillin may result from ionic rather than steric constraints. A molecular model of the Val-237 TEM-2 mutant suggests possible electrostatic interaction between Glu-171 and the carboxylic group of the side chain of carbenicillin.

Amino Acid Sequence↗
PubMed1994

Putative dimeric organization of nuclear receptor hormone-binding domains, deduced from hydrophobic cluster analysis.

2D hydrophobic cluster analysis (HCA) protein sequence processing, efficient at low levels of sequence identity, leads to a coherent scheme for the structural organization of the hormone-binding domains (HBDs) of nuclear receptors. The typical serine protease inhibitor (serpin) fold, previously proposed, is confirmed as a likely framework for the hormone-binding domain and leads to a logical dimerization. Furthermore, homo- or hetero-dimerization creates sites where hormone could likely be bound, itself being an active component of the dimerization. This model fulfils many of the biochemical and biological data.

Amino Acid Sequence↗
PubMed1987

Oxygen transport and metabolism in the conscious lamb: the effects of hypoxemia.

We studied the response of O2 consumption, systemic O2 transport, arterial blood lactate concentration, base deficit, and respiratory exchange ratio (CO2 production/O2 consumption) to graded alveolar hypoxia (fractional concentration of inspired oxygen 0.21, 0.16, 0.12, and 0.08) in seven intact, conscious chronically catheterized lambs at less than 1 wk after birth, at 25-40 days and at greater than 40 days. To test whether there was an age related difference in the metabolic response to a decline in O2 transport due to hypoxemia, we related the changes in blood lactate and base deficit to the systemic O2 transport and to the fractional change in O2 consumption. Systemic O2 transport and O2 consumption decreased with severe hypoxemia, while lactate concentration and respiratory exchange ratio increased in all age groups. The changes in base deficit were not significant. When the hypoxemia-induced reduction in O2 consumption was less than 15% of the baseline value (at fractional concentration of inspired oxygen 0.21) there was no elevation in lactate concentration; however, when O2 consumption was reduced by more than 15%, lactate concentration consistently increased by more than 1 mmol/liter. There were no apparent differences amongst the age groups in this response. Therefore, the newborn lamb does show metabolic consequences of a fall in O2 consumption with hypoxemia which is similar to the older sheep, however, there is a "buffer zone" in which O2 consumption may decrease before evidence of tissue hypoxia can be found. The mechanism by which O2 consumption can decrease without accumulation of lactate remains speculative.

Age Factors↗
PubMed1984

Effects of alterations of oxygen transport on the neonate.

In the foregoing discussion we have attempted to provide an overview of much of the information available on the effects of changes in systemic oxygen transport on the neonatal and young subject. Using data synthesized from both human and animal studies, we have described the normal developmental changes and the findings of studies in which oxygen transport has been acutely altered by experimental means. This was intended to highlight the potentially delicate balance that can occur between oxygen supply and utilization during the critical period of rapid growth after birth. Finally, using the left-to-right shunt as an example, we have tried to show how a common pathologic condition can impair oxygen transport at multiple sites, and how normal development can make matters worse. It is anticipated that from an understanding of both normal and abnormal physiology, we will be able to develop rational approaches to the management of infants in whom the oxygen transport system has been stressed beyond its reserve.

2,3-Diphosphoglycerate↗