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Biomedical subjects

F Bernard

Publications and source records attributed to F Bernard.

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

Use of recombinant human deoxyribonuclease (DNase) for processing of a thawed umbilical cord blood transplant in a patient with relapsed acute lymphoblastic leukemia.

This case report describes for the first time the use of a recombinant human enzyme deoxyribonuclease (rhDNase) containing solution for the processing of a thawed umbilical cord blood (UCB) unit prior to successful transplantation to avoid cell losses by clotting phenomena. A 6-year-old boy received an unrelated 2/6 HLA antigen mismatched UCB transplant for high-risk Burkitt type acute lymphoblastic leukemia. The UCB unit was provided as a volume-reduced sample after buffy coat separation with a final volume of 36 ml. To avoid the loss of nucleated cells due to cell clumping during thawing procedure cells were washed with a solution containing the rhDNase. No visible clotting of the resuspended unit occurred, and the patient was transplanted with 2.9x10(7) nucleated cells/kg body weight without any acute or chronic side effects due to rhDNase. On day +35, PCR analysis of bone marrow aspirate showed complete chimerism, and the child engrafted with an absolute neutrophil count greater than 0.5x10(9)/l on day +47. Platelet transfusion independence was achieved on day +120. In conclusion, the supplementation of rhDNase to the washing and resuspension solutions of a thawed UCB unit is effective to prevent cell losses prior to transplantation. However, further investigations must be performed to confirm the safety of this procedure.

Blood Transfusion↗
PubMed2002

[Screening of the abdominal aortic aneurysms during an echocardiography].

We examined the abdominal aorta by ultrasound in 1106 patients during transthoracic echocardiography, whatever the reason of the echocardiography, to track abdominal aortic aneurysms. The study group comprised 822 men and 284 women. We found 88 patients having an abdominal aorta with a diameter of more than 23 mm and 11 patients with a diameter of more than 35 mm. Ninety sixteen per cent of the patients having an aortic ecstasy are more than fifty years old. Ther are more smokers among the patients having an aortic ecstasy. In conclusion, the track of the ecstasies and the abdominal aortic aneurysms is easily realizable during an echocardiography and presents a good rentability.

Adolescent↗
PubMed2001

Identification of living oligodendrocyte developmental stages by fractal analysis of cell morphology.

The Mandelbrot's fractal dimension (D), a measure of shape complexity, has been used to quantify the complex morphology of living cells. Previous studies on glial cells have shown that as cells increase in morphological complexity, their "D" value increases, suggesting that "D" could be used to estimate their stage of differentiation. In the present study the box-counting method was used to calculate the "D" values of rat cerebellar oligodendrocytes during their differentiation in primary culture. These values were correlated with the immunoreactivity of cells to antigenic markers commonly used for assessing their stages of differentiation: A2B5, O4 and anti-galactocerebroside (Gal-C). Our results show that changes of the fractal dimension during differentiation follow the well known pattern of markers expression by these cells. These results demonstrate that A2B5-, O4-, and Gal-C-expressing oligodendrocytes can be confidently estimated from their respective fractal dimension values. Based on this immunocytochemical calibration, the calculation of "D" allows an easy and fast determination of the developmental stage of living (unstained) oligodendrocytes before the study of their physiological characteristics. Using this method we precisely identified living oligodendrocyte progenitors and early pro-oligodendrocytes expressing voltage-activated sodium currents that is a common characteristic of these two immature developmental stages (Sontheimer et al. [1989b] Neuron 2:1135-1145).

Aging↗
PubMed2001

Contributions of frontal and medial temporal regions to verbal episodic memory: a PET study.

Using PET, subtraction and correlation analysis were jointly employed to determine the specific and complementary contributions of frontal and medial temporal regions to verbal episodic encoding and retrieval processes. Subtraction analysis highlighted prefrontal rCBF increases which were predominantly left-sided during intentional encoding and exclusively right-sided during retrieval, the latter being moreover associated with bilateral precuneus activation. However, significant correlation between rCBF values obtained during intentional encoding and performance scores obtained during retrieval concerned, among other regions, the left parahippocampal gyrus, which indicated that the higher the neuronal activity in this medial temporal region during encoding, the better the retrieval performance.

Adult↗
PubMed2001

Ubiquitin and the SCF(Grr1) ubiquitin ligase complex are involved in the signalling pathway activated by external amino acids in Saccharomyces cerevisiae.

In response to external amino acids, the permease-like sensor Ssy1 of Saccharomyces cerevisiae activates a pathway leading to transcriptional induction of several permease genes including AGP1 and PTR2. We previously reported that AGP1 induction requires Grr1, the F-box protein part of the SCF(Grr1) ubiquitin-ligase complex. We show here that ubiquitin, other components of SCF(Grr1) and the ubiquitin-conjugating enzyme Cdc34 are essential for AGP1 and PTR2 induction. This suggests that transduction to these genes of the amino acid signal generated by Ssy1 involves an SCF(Grr1)-catalysed ubiquitination step.

Amino Acid Transport Systems↗
PubMed2001

[Family socioeconomic deprivation and vulnerability in the pediatric emergency room: evaluation and management].

OBJECTIVE: The aim of this study was to evaluate the importance of socioeconomic deprivation and other forms of vulnerability in families attending the pediatric emergency unit (PEU). It was based on a five-level classification of family types and an analysis of responses provided by the French healthcare system. METHOD: The prospective study involved 150 families admitted to the PEU on the basis of open-response interviews that analyzed demographic and socio-economic characteristics, motivations for consultation, the child's quality of life, family problems experienced by the parents, and their support network. RESULTS: Five categories of families were defined as follows: complete destitution necessitating immediate social measures (0.7%); acknowledged and well-managed economic deprivation (13.3%), unacknowledged and/or complex economic deprivation with a significant deterioration in the quality of life (22.2%), familial psychological vulnerability without economic deprivation (30.4%), and families without any apparent problems (33.7%). Consultation at the PEU appears to be a multifactorial phenomenon motivated by socioeconomic, psychological and cultural factors. This phenomenon is connected with the present-day imbalance in the healthcare system, which does not adequately respond to the needs of vulnerable families. CONCLUSION: This survey contributes to the current reflection on the integration of psychosocial factors in child healthcare at both the hospital and local community level. The method described herein has determined the factors of vulnerability and the risks of economic deprivation. It can contribute to the development of improved communication and cooperation between practitioners, the hospital and local social workers.

Adult↗
PubMed2001

Genetic analysis of the signalling pathway activated by external amino acids in Saccharomyces cerevisiae.

The permease-like amino acid sensor Ssy1p of Saccharomyces cerevisiae is required for transcriptional induction, in response to external amino acids, of several genes encoding peptide and amino acid permeases. Among them is AGP1 encoding a low-affinity, broad-specificity amino acid permease important for the utilization of amino acids as a nitrogen source. We report here data from experiments aimed at identifying components of the signalling pathway activated by Ssy1p. Overproduction of the large amino-terminal tail of Ssy1p interferes negatively with the induction of AGP1 in wild-type cells. Furthermore, overproduction of this domain can relieve growth defects of a ssy1 null strain, indicating that the N-terminal tail of Ssy1p is an important functional element of the pathway. Consistent with a role for Ssy1p in the recognition of amino acids, a mutant form of the protein with a Thr to Ile substitution in the eighth predicted transmembrane domain is competent for the induction of AGP1 by leucine but not by other amino acids. In a screen for other mutants defective in the Ssy1p pathway, we confirmed that PTR3 and SSY5 encode additional factors essential for AGP1 expression in response to multiple amino acids. Data obtained by overproducing Ptr3p and Ssy5p in ssy1Delta, ptr3Delta and ssy5Delta mutants suggest that Ptr3p acts downstream from Ssy1p and Ssy5p downstream from Ptr3p in the transduction pathway. Furthermore, two-hybrid experiments indicated that Ptr3p interacts with Ssy5p and that Ptr3p can self-associate. Finally, the Cys-6-Zn2 transcription factor Uga35p/Dal81p required for the induction of AGP1 is also essential for the expression of two other genes under Ssy1p-Ptr3p-Ssy5p control, namely BAP2 and PTR2, suggesting that the protein is yet another component of the amino acid signalling pathway.

Amino Acid Transport Systems, Neutral↗
PubMed2001

Diastolic dysfunction is predictive of difficult weaning from cardiopulmonary bypass.

Diastolic function is receiving more attention since echocardiographic measurements were developed and have become widely available. The importance and significance of diastolic dysfunction (DD) observed before cardiac surgery and its relationship with adverse outcomes, such as difficult separation from cardiopulmonary bypass (CPB), have not been fully explored. In this study, we hypothesize that DD can be a predictor for the need of inotropic support to successfully separate from CPB. Ninety-two consecutive patients underwent surgery during the study period. Twenty-six patients were excluded. From the remaining 66 patients, 52 had coronary artery bypass grafting alone and 14 combined procedures, valvular surgery, and reoperations (redo). Systolic and diastolic function was evaluated by two experts blinded as to the clinical data except for the age. The evaluation of diastolic function was done according to published guidelines. The demographic, echocardiographic, and hemodynamic variables were entered in a logistic regression analysis to determine which variables were independent predictors of difficult separation from CPB and the need for postoperative vasoactive support. DD was present in 20 patients (30%). Patients with DD had lower weight (P = 0.046), less frequent coronary artery bypass grafting alone (P = 0.0004), more myocardial infarction before surgery (P = 0.02), higher regional wall motion score index (P = 0.0002), and larger left ventricle (P = 0.03). Total CPB time (P = 0.004) and ischemic time (P = 0.007) were longer in the DD group. Patients with DD required more frequent inotropic support at the end of surgery (P = 0.006) and up to 12 h after surgery (P = 0.003). Multivariate logistic regression identified female sex, DD, and total CPB time as predictive of difficult weaning and inotropic requirements up to 12 h after surgery.

Aged↗
PubMed2001

[Micrometastases in pediatric oncology].

Metastatic relapse in children with solid tumors is mainly caused by systemic pretreatment dissemination of occult tumor cells. Therefore the initial detection of undetected metastases could have a clinical impact on the prognosis (i.e. new initial staging) and therapy for children with cancer. At later stage it is useful to determine the presence and change in the number of residual malignant cells in order to adjust and/or select adjuvant therapies and techniques (i.e. autologous bone marrow transplantation, leukapheresis.). Over the past decade, sensitive immunocytochemical and molecular assays have been developed which permit the identification of disseminated cancer cell. Actually tumor cell contamination can be detected in bone marrow or in peripheral blood of children with following cancers: neuroblastoma, Ewing tumor, alveolar rhabdomyosarcoma, PNETs. In this review, focus is on the recent technical achievements in the detection of occult cancer cells in bone marrow and in blood and a discussion of their usefulness for clinical trials.

Antibodies, Monoclonal↗
PubMed2001

Hormonal variation in bitches after early or mid-pregnancy termination with aglepristone (RU534).

Seven bitches in early pregnancy (12.8 +/- 3.8 days after ovulation; group 1) and seven bitches in mid-pregnancy (32.0 +/- 1.53 days after ovulation; group 2) were used in this study. For each group, five bitches were treated with 0.10 mg aglepristone (Alizine) kg-1 and this dose was repeated 24 h later. Two control bitches received a placebo. Blood samples were collected at 6 h intervals to determine plasma concentrations of progesterone, dihydro-keto prostaglandin F2 alpha (PGFM), oxytocin, prolactin and cortisol. Parturition occurred in the four control bitches. All bitches treated with aglepristone aborted. In group 1, embryonic death occurred; in group 2, fetal expulsion occurred 60-132 h after administration of aglepristone. After pregnancy termination, the interoestrous interval of aglepristone-treated bitches was significantly shorter than that before treatment. Treatment with aglepristone did not modify plasma concentrations of progesterone, prostaglandin, oxytocin or cortisol within 24 h after its administration, but it induced, in mid-pregnancy (group 2) a discharge of prolactin within 12 h after its administration. As an abortifacient, aglepristone acted on the uterus and, therefore, did not have direct or immediate luteolytic properties. Termination of pregnancy occurred with high plasma progesterone concentrations. Fetal expulsion was characterized by an increase in the concentration of PGFM, but oxytocin and cortisol remained at basal concentrations.

Abortifacient Agents↗
PubMed2000

Further demonstration of the diversity of chromosomal changes involving 2p23 in ALK-positive lymphoma: 2 cases expressing ALK kinase fused to CLTCL (clathrin chain polypeptide-like).

Anaplastic lymphoma kinase (ALK)-positive lymphomas are characterized by expression of a hybrid protein, comprising the cytoplasmic portion of the ALK tyrosine kinase fused to a partner protein. This hybrid kinase is often encoded by the nucleophosmin (NPM) NPM-ALK fusion gene resulting from the (2;5)(p23;q35) chromosomal translocation. However, the ALK gene at 2p23 may also be involved in 2 variant translocations, namely t(1;2)(q25;p23) and t(2;3)(p23;q21), which create the TPM3-ALK and TFG-ALK fusion genes, respectively. We report here 2 lymphomas with an unusual finely granular cytoplasmic ALK staining pattern, clearly different from the pattern observed in ALK-positive lymphomas carrying NPM-ALK or its variants. A cloned complementary DNA sequence from 1 of these 2 lymphomas contained the ALK gene fused to the second clathrin heavy chain gene (also referred to as clathrin heavy polypeptide-like gene) (CLTCL). The distinctive granular cytoplasmic staining pattern for ALK was likely to be due to binding of the fusion protein to clathrin-coated vesicles. The CLTCL gene is constitutively expressed in lymphoid cells and therefore presumably contributes an active promoter for the CLTCL-ALK gene. The fusion protein had a molecular weight (250 kd) that differs from all known ALK products, and it was autophosphorylated in an in vitro kinase assay, confirming that it is constitutively active and hence capable of contributing to malignant transformation. These 2 cases, therefore, represent a hitherto undescribed mechanism of ALK activation in lymphoma and further illustrate the diversity of fusion partners for the ALK gene.

Amino Acid Sequence↗
PubMed2000

Simultaneous IR and time-resolved X-ray diffraction measurements for studying self-sustained reactions.

Self-propagating high-temperature synthesis provides an attractive practical method for producing advanced materials such as ceramics, composites and intermetallics. This kind of reaction has been investigated in situ using time-resolved X-ray diffraction, with an X-ray synchrotron beam (D43 beamline, LURE, Orsay) coupled to simultaneous IR thermography to study structural transformations and thermal evolution. With short acquisition times (30 ms per pattern) it has been possible to observe several steps before obtaining compounds. Two different compound formations have been described: (i) the different steps of reaction, aluminium melting, subsequent temperature increase and fast reaction between Al and Ni at such temperatures that only Ni and AlNi are solid and all other compositions are liquid and well identified; (ii) the formation of FeAl. Here, a portion of the iron seems to transform into its allotropic phase and this transition stabilizes the reaction temperature at approximately 1173 K. In addition, the aluminium melting during the reaction explains why the nanostructure induced by the mechanical activation is maintained in the end product.

Journal Article↗
PubMed1999

[Sinus histiocytosis (Destombes-Rosai-Dorfman disease) revealed by extranodal spinal involvement].

BACKGROUND: Sinus histiocytosis with massive cervical lymphadenopathy (Rosai-Dorfman disease) is a non-neoplastic lymphoproliferative disorder. Extranodal involvement, especially of the nervous system, is unusual. We report a case revealed by neurological symptoms. CASE REPORT: A 10-year-old girl presented with paraparesis due to a dural extramedullary mass on magnetic resonance imaging. Massive cervical lymphadenopathy appeared secondarily. Radiological investigations showed mediastinal, paranasal sinus and lower eyelid involvement. The diagnosis of Rosai-Dorfman disease was established histologically and by immunohistochemical studies of nodal lesions by the demonstration of characteristic sinus histiocytosis with sheets of S-100 protein and CD-68 positive large histiocytes displaying lymphocyte phagocytosis. A dramatic response occurred with complete resolution of all clinical findings after treatment with corticosteroids and etoposide, although neurological lesions were unchanged on magnetic resonance imaging. CONCLUSION: Despite its rarity, this case underlines the unknown pathogenesis of this disease (immune dysfunction?) and the difficulties of treatment (choice of chemotherapeutic agents, duration).

Adrenal Cortex Hormones↗
PubMed1999

Euglycemic hyperinsulinemic clamp to assess posthepatic glucose appearance after carbohydrate loading. 1. Validation in pigs.

BACKGROUND: Precise knowledge of the rate of glucose absorption after meal feeding requires invasive methods in humans. OBJECTIVE: This study aimed to validate in an animal model a technique combining the euglycemic hyperinsulinemic clamp and oral carbohydrate loading (OC-Clamp) as a noninvasive procedure to quantify the posthepatic appearance of glucose after oral carbohydrate loading. DESIGN: Twenty-one pigs were fitted with arterial, jugular, portal, and duodenal catheters and a portal blood flow probe. At glucose clamp steady state, duodenal glucose (0.9 g/kg; DG-Clamp) and oral carbohydrate (140 g corn or mung bean starch as part of a mixed meal; OC-Clamp) were administered while the glucose infusion was progressively reduced to compensate for the incremental posthepatic appearance of glucose. [3-3H]glucose was used to assess the glucose turnover rate. RESULTS: Hepatic glucose production was totally suppressed by insulin infusion, and the whole-body glucose turnover rate remained stable during glucose absorption. The incremental portal appearance of glucose after the DG load was not altered by hyperinsulinemia, and the cumulative posthepatic appearance of glucose was 63 +/- 3% (x +/- SEM) of the DG load. The net hepatic portal appearance of glucose remained constant during absorption (34 +/- 3% of the load). After the OC load, the respective portal appearance rates of glucose were significantly different between carbohydrate sources; however, the rates paralleled those of the posthepatic appearance of glucose. Again, net hepatic glucose uptake expressed as portal appearance was similar for both carbohydrates. CONCLUSIONS: The results validate the OC-Clamp method to monitor the posthepatic appearance of glucose after carbohydrate ingestion and to discriminate between different carbohydrate sources. The results suggest that the technique be used in humans.

Analysis of Variance↗
PubMed1999

Amino acid signaling in Saccharomyces cerevisiae: a permease-like sensor of external amino acids and F-Box protein Grr1p are required for transcriptional induction of the AGP1 gene, which encodes a broad-specificity amino acid permease.

The SSY1 gene of Saccharomyces cerevisiae encodes a member of a large family of amino acid permeases. Compared to the 17 other proteins of this family, however, Ssy1p displays unusual structural features reminiscent of those distinguishing the Snf3p and Rgt2p glucose sensors from the other proteins of the sugar transporter family. We show here that SSY1 is required for transcriptional induction, in response to multiple amino acids, of the AGP1 gene encoding a low-affinity, broad-specificity amino acid permease. Total noninduction of the AGP1 gene in the ssy1Delta mutant is not due to impaired incorporation of inducing amino acids. Conversely, AGP1 is strongly induced by tryptophan in a mutant strain largely deficient in tryptophan uptake, but it remains unexpressed in a mutant that accumulates high levels of tryptophan endogenously. Induction of AGP1 requires Uga35p(Dal81p/DurLp), a transcription factor of the Cys6-Zn2 family previously shown to participate in several nitrogen induction pathways. Induction of AGP1 by amino acids also requires Grr1p, the F-box protein of the SCFGrr1 ubiquitin-protein ligase complex also required for transduction of the glucose signal generated by the Snf3p and Rgt2p glucose sensors. Systematic analysis of amino acid permease genes showed that Ssy1p is involved in transcriptional induction of at least five genes in addition to AGP1. Our results show that the amino acid permease homologue Ssy1p is a sensor of external amino acids, coupling availability of amino acids to transcriptional events. The essential role of Grr1p in this amino acid signaling pathway lends further support to the hypothesis that this protein participates in integrating nutrient availability with the cell cycle.

Amino Acid Sequence↗