Biomedical subjects

O Bernard

Publications and source records attributed to O Bernard.

At least 91 records · Page 5Linked to original sources

PubMed1997

The human protein p19ARF is not detected in hemopoietic human cell lines that abundantly express the alternative beta transcript of the p16INK4a/MTS1 gene.

The p16/MTS1/CDKN2 gene on human chromosome band 9p21 encodes two unrelated proteins: p16INK4a, a specific inhibitor of the cyclin D-dependent kinases CKD4 and CDK6, and the structurally unrelated p19ARF protein that arrests cell growth in G1/S and also in G2/M. By use of polyclonal antibodies, the human p19ARF (hp19ARF) protein has been identified in the nucleus of various cells including normal cultured fibroblasts. The level of this protein did not fluctuate throughout the cell cycle and was more elevated in fibroblasts with limited or arrested growth, suggesting that p19ARF accumulated in presenescent or senescent cells. Interestingly, hp19ARF was not detected in several hemopoietic tumor cell lines (mainly of B-type lymphoid origin) that expressed abundant amounts of the p16beta transcript. This finding indicates that in certain tumors, the expression of hp19ARF RNA and protein may be uncoupled. Furthermore, it suggests that disruption of a translational mechanism may be involved in the inactivation of hp19ARF.

Animals↗

PubMed1997

FGF plays a subtle role in oligodendrocyte maintenance in vivo.

Numerous in vitro studies indicate that fibroblast growth factors (FGFs) play a role in both the development and maintenance of oligodendrocytes. Addition of FGF to mature oligodendrocytes in culture was reported to downregulate the expression of genes encoding proteins of the myelin sheath and to induce a loss of myelin compaction. In this study, a model was developed to functionally block FGF signaling in oligodendrocytes in vivo, by generating transgenic mice expressing a dominant-negative FGF receptor (FGFR1), under the control of the myelin basic protein (MBP) promoter. To demonstrate the effectiveness of this model, truncated FGFR1 was first overexpressed in an FGF-responsive cell line in vitro. It was confirmed that FGF-signalling was blocked in these cells. Subsequently, five independent transgenic lines ("MBP-FRD") were generated. Three lines expressing the highest level of the transgene were further studied. Initial investigation by Western blot and light microscopic analyses revealed no apparent alterations in myelination of the MBP-FRD mouse brains. However, ultrastructural analysis of myelinated optic nerve fibres from two independent MBP-FRD lines revealed a significant increase in myelin thickness as a function of fibre diameter for both transgenic lines (13% and 16% increase). This increase in myelin thickness was not accompanied by alterations in myelin compaction. These results support the idea that FGF signaling in oligodendrocytes plays a role in the modulation of axon myelination in vivo.

Animals↗

PubMed1997

[Cirrhosis in children].

Chronic cholestasis, starting early in life, inborn errors of metabolism and chronic hepatitis are the main causes of cirrhosis in children. Precise identification of the cause is crucial because effective therapy is available for many of them. Close follow-up is necessary for all the child's life to prevent, detect and manage the complications and to decide on liver transplantation when no effective therapy is available. Results of liver transplantation in children with cirrhosis indicate that close to 80% of children will be alive 10 years after surgery. Liver transplantation must be carried out before signs of liver failure are present.

Age Factors↗

PubMed1997

A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFR beta oncoprotein.

TEL is a novel member of the ETS family of transcriptional regulators which is frequently involved in human leukemias as the result of specific chromosomal translocations. We show here by co-immunoprecipitation and GST chromatography analyses that TEL and TEL-derived fusion proteins form homotypic oligomers in vitro and in vivo. Deletion mutagenesis identifies the TEL oligomerization domain as a 65 amino acid region which is conserved in a subset of the ETS proteins including ETS-1, ETS-2, FLI-1, ERG-2 and GABP alpha in vertebrates and PNTP2, YAN and ELG in Drosophila. TEL-induced oligomerization is shown to be essential for the constitutive activation of the protein kinase activity and mitogenic properties of TEL-platelet derived growth factor receptor beta (PDGFR beta), a fusion oncoprotein characteristic of the leukemic cells of chronic myelomonocytic leukemia harboring a t(5;12) chromosomal translocation. Swapping experiments in which the TEL oligomerization domain was exchanged by the homologous domains of representative vertebrate ETS proteins including ETS-1, ERG-2 and GABP alpha show that oligomerization is a specific property of the TEL amino-terminal conserved domain. These results indicate that the amino-terminal domain conserved in a subset of the ETS proteins has evolved to generate a specialized protein-protein interaction interface which is likely to be an important determinant of their specificity as transcriptional regulators.

Amino Acid Sequence↗

PubMed1997

Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis.

Progressive familial intrahepatic cholestasis (PFIC) is a lethal inherited childhood cholestasis of hepatocellular origin. Different subtypes of PFIC have been described according to serum gamma-glutamyl transpeptidase (GGT) activity. There is currently no effective medical therapy available for children with PFIC. We report on 39 patients with PFIC who received ursodeoxycholic acid (UDCA) orally (20-30 mg/kg b.w./day) for a period of 2 to 4 years. Group 1 (n = 26) consisted of children with normal GGT activity, and group 2 (n = 13) of children with high GGT activity. Within group 1, liver tests normalized in 11 children, improved in 5, and stabilized or worsened in 10. Within group 2, liver tests normalized in six children, improved in four, and stabilized or worsened in three. Improvement of parameters was associated with an enrichment of the circulating pool of bile acids with UDCA. Hepatosplenomegaly and pruritus disappeared or diminished in children in whom liver tests normalized. In nine of these children, liver tests worsened and normalized again after stopping and restarting UDCA. Liver histology assessed in four children after normalization of liver tests and 2 years of treatment showed a decrease in fibrosis. We conclude that UDCA should be considered in the initial therapeutic management of children with PFIC, because it appears effective in resolving or improving the liver function and the clinical status of a fair proportion of children. Chronic UDCA therapy might thus avoid the need for liver transplantation in some children with PFIC.

Alanine Transaminase↗

PubMed1997

Rationale and technical constraints of a tertiary liver transplantation.

Because of the current shortage of donor organs, the routine performance of tertiary liver transplantation (LT) may be questioned. In this study, the indications of tertiary LT are discussed, paying particular attention to intraoperative technique. Of 501 LTs performed from 1986 to 1995, eight (1.6%) were tertiary LTs. Three patients underwent an emergent third LT because of associated hepatic artery and portal vein thromboses (n = 2) or hyperacute rejection (n = 1). Five patients had an elective third LT for ischemic cholangitis (n = 4) or chronic rejection (n = 1). The 3 patients who underwent retransplantation emergently died early from multiple-organ failure. Because of previous surgery and subsequent technical difficulties, the third LT in the remaining 5 patients required unroutine surgical procedures including the following: intrapericardial control of the suprahepatic vena cava (n = 1), "en bloc" clamping of both the infrahepatic vena cava and the hepatic pedicle (n = 1), arterial reconstruction onto the aorta via an aortoiliac conduit (n = 5), and aortic resection with aortoaortic prosthetic reconstruction (n = 1). Of these 5 patients, 4 required reoperation because of bowel perforation (n = 5) or intraperitoneal bleeding (n = 1). The 5 patients (62%) who were regrafted electively are alive and well after a median follow-up of 45 months. A third LT can be reasonably offered to selected young recipients if performed electively. Tertiary LT may require unroutine surgical procedures and may lead to severe morbidity.

Adult↗

PubMed1997

Neonatal and delayed-onset liver involvement in disorders of oxidative phosphorylation.

Inborn errors of oxidative phosphorylation have been recognized as possible causes of hepatic failure in the neonate, and respiratory enzyme deficiencies have been described in the liver of affected individuals. On the basis of a series of 22 cases, we describe respiratory enzyme deficiency as a cause of early-onset fatal hepatic failure with frequent neurologic involvement. In addition, we have identified a delayed-onset form of hepatic failure with a milder clinical course and inconstant neurologic involvement. Thus we suggest that genetic defects of oxidative phosphorylation be considered as a cause of liver dysfunction in infancy, regardless of the severity of the disease.

Alanine Transaminase↗

PubMed1997

Protein C, protein S and antithrombin III in children with portal vein obstruction.

BACKGROUND/AIMS: Portal vein obstruction is the most common single cause of portal hypertension in children and its cause is unknown in most instances. The aim of the present study was to evaluate the incidence of protein C, protein S and antithrombin III deficiencies and to screen for possible genetic deficiencies of these proteins. METHODS: A prospective study was undertaken in 20 consecutive children with portal vein obstruction, their parents and 20 matched healthy children. RESULTS: Children with portal vein obstruction displayed a reduction in protein C (p<0.05), protein S (p<0.0001), and antithrombin III (p<0.001) activities as compared with controls. Protein C and protein S activities were below 60% in nine and eleven of the children with portal vein obstruction, respectively, and antithrombin III activities were below or equal to 85% in ten of them. Repeated assay of protein C activity in seven children following a surgical portosystemic shunt showed a decrease as compared with preoperative values. Protein C, protein S and antithrombin III were normal in all parents, except two mothers in whom the levels of protein S activity and protein S antigen were found to be either below or at the lower limit of the normal range. CONCLUSIONS: These results indicate that protein C, protein S and/or antithrombin III deficiencies are frequently found in children with portal vein obstruction but are not likely to be of genetic origin in most cases.

Adolescent↗

PubMed1997

[Epithelioid sarcoma. Diagnostic and therapeutic aspects apropos of a coccygeal localization].

A rare case of epithelioid sarcoma of the coccyx is described. A 23-year-old man had coccidynia for 2 years, becoming permanent. The patient underwent an "en bloc" excision including a resection of the extremity of the coccyx. Postoperatively, six cycles of a chemotherapy combining ifosfamide and adriamycine were alternated with a 60 Gy external beam radiotherapy. The patient remains free of disease 9 months after the operation. We review the clinical characteristics and treatment of epithelioid sarcoma.

Adult↗

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

Liver failure in children with hepatitis A.

There have been very few reports dealing with liver failure related to hepatitis A in children. Moreover, the criteria usually used for selecting patients with fulminant hepatitis A for liver transplantation have not been evaluated in children. Therefore, the current study was conducted retrospectively in a single French urban pediatric liver transplantation center to serve as a reminder of the potential severity of hepatitis A in children and to identify predictors of outcome. Children were selected by chart review using a data base system and were grouped according to outcome for analyses purposes. Over a 15-year period, 24 children with hepatitis A showed evidence of liver failure, including 6 children who did not develop hepatic encephalopathy, 7 children in whom encephalopathy occurred but resolved spontaneously, and 11 children in whom death or liver transplantation was the outcome. The mean age at onset was 6.5 years. Those with the most rapid onset of liver failure from onset of jaundice had the best chance of recovery without developing encephalopathy. Otherwise, no predictive factors of outcome were found at onset of liver failure. Among the 18 children who developed encephalopathy, the best early prognostic indicator of a poor outcome irrespective of the grade of encephalopathy, appeared to be a prothrombin time level below 21% of normal combined with a serum bilirubin level above 400 micromol/L. Therefore, these two prognostic indicators may be helpful in deciding liver transplantation in children with hepatitis A-induced fulminant liver failure.

Adolescent↗

PubMed1997

Plasma myosin and creatine kinase time-course after a concentric-eccentric field exercise.

The effect of a concentric (uphill run)-eccentric (downhill run) field exercise of 22.3 km long was examined in five healthy male volunteers to compare the time course of changes in plasma creatine kinase (CK) activity and beta myosin heavy chain (beta MHC) concentration observed during the recovery. CK and beta MHC were examined in blood sampled before exercise, immediately and 5 hours after exercise ceased. Screenings were conducted 1, 2, 3, 4, 5 and 7 days later. For every subject, the peak of plasma CK was transient and observed within the first 24 hours of recovery. In contrast to CK changes, plasma beta-MHC elevation was delayed and the peak, also transient, was observed the second or the third day after the exercise. The highly significant relationship between individual values of CK and beta MHC (P < 0.001) demonstrates that beta MHC could be used as a marker of skeletal muscle damage after acute exercise.

Adult↗

PubMed1997

NSE-bcl-2 transgenic mice, a model system for studying neuronal death and survival.

Bcl-2 is a crucial regulator of cell survival and death. We have recently demonstrated that transgenic mice overexpressing the human Bcl-2 protein specifically in their neurons have an increased number of neuronal cells which can survive in tissue culture in the absence of neurotrophic factors. In order to understand why only some neurons can be rescued from developmental and neurotrophic factor deprivation-induced death, we have studied the expression pattern of the transgene during embryonic development an in adulthood. We have demonstrated that transgene expression starts in embryos at E12.5 and that only half of the sensory neurons of the dorsal root ganglia expressed detectable levels of the human Bcl-2. These results may explain why only 40% of the sensory neurons survived in tissue culture in the absence of neurotrophic factors.

Aging↗

PubMed1997

Determinants of life span after Kasai operation at the era of liver transplantation.

The aim of this work is to determine the influence of age, extrahepatic biliary lesions pattern (EHBP) and association to polysplenia syndrome (PS) on 10 years outcome of 164 patients with biliary atresia (BA) treated from 1984 to 1992 by initial Kasai operation (KO) and secondary liver transplantation (LT) when necessary. Actuarial crude survival without or after LT (CS), actuarial survival with native liver (NLS) and jaundice-free actuarial survival with native liver (JFS) were calculated from 1 to 10 years versus age (under/over 45 days), EHBP (favorable/ unfavorable) and PS (no/yes). Overall 10-year CS is 70%, overall 10-year NLS and JFS are 14%. In univariate analysis, age at KO under 46 days, favorable EHBP (BA with patent gallbladder, and/or cystic dilatation of extrahepatic bile duct, or BA restricted to choledocus), and absence of PS are significant determinants of a better outcome regarding CS, NLS and JFS. EHBP is more discriminant than age. Influence of PS in this series is redundant with that of EHBP since 11/11 patients with PS had unfavorable EHBP.

Age Factors↗

PubMed1996

[Formal concept analysis].

Formal Concept Analysis plays a fundamental role in different fields of research and it is widely used in applied sciences in the last years. In the present paper the authors show in detail how it can be applied to the study of results obtained in clinical practice.

Anti-Bacterial Agents↗

PubMed1996

bcl-w, a novel member of the bcl-2 family, promotes cell survival.

The prototypic mammalian regulator of cell death is bcl-2, the oncogene implicated in the development of human follicular lymphoma. Several homologues of bcl-2 are now known. Using a PCR-based strategy we cloned a novel member of this gene family, denoted bcl-w. The gene, which is highly conserved between mouse and human, resides near the T-cell antigen receptor alpha gene within the central portion of mouse chromosome 14 and on human chromosome 14 at band q11. Enforced expression of bcl-w rendered lymphoid and myeloid cells refractory to several (but not all) cytotoxic conditions. Thus, like Bcl-2 and Bcl-x, the Bcl-w protein promotes cell survival, in contrast to other close homologues, Bax and Bak, which facilitate cell death. Comparison of the expected amino acid sequence of Bcl-w with that of these relatives helps to delineate residues likely to convey survival or anti-survival function. While expression of bcl-w was uncommon in B or T lymphoid cell lines, the mRNA was observed in almost all murine myeloid cell lines analysed and in a wide range of tissues. These findings suggest that bcl-w participates in the control of apoptosis in multiple cell types. Its functional similarity to bcl-2 also makes it an attractive candidate proto-oncogene.

Amino Acid Sequence↗

PubMed1996

Structure and chromosomal localization of the genomic locus encoding the Kiz1 LIM-kinase gene.

We have cloned and characterized the mouse gene encoding Kiz1/Limk1, a new member of the zinc-finger LIM family that also has a kinase domain. The gene encompasses 25 kb of the mouse genome, and the organization of its 16 exons does not correlate with its functional domains. The promoter region of Kiz1/Limk1 was identified by cloning a 1.06-kb genomic fragment upstream from the first ATG in a promotorless CAT vector. This construct was demonstrated to drive CAT expression in Jurkat cells. The promoter sequence lacks conventional TATA and CAAT motifs but contains consensus binding sequences for several transcriptional regulators implicated in control of transcription in many different cell types, including Sp1, Ets, and E2A. Analysis of the chromosomal localization of KIZ1/LIMK1 indicates that it lies on human chromosome 17 in the region 17q25 and on mouse Chromosome 5, band G2.

Animals↗

PubMed1996

Incidence and characterization of MLL gene (11q23) rearrangements in acute myeloid leukemia M1 and M5.

To determine the incidence of MLL rearrangement in acute myeloid leukemia (AML) French-American-British (FAB) type M1 and to evaluate optimal screening strategies for the characterization of such abnormalities, we analyzed specimens from 41 patients with AML by Southern blotting with two MLL genomic probes and compared the capacities of reverse transcription-polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH) to identify the types of rearrangement found in AML M1 with those observed in AML M5. MLL rearrangement was found in 6 of 29 (20%) AML M1 and 6 of 10 AML M5 cases. RT-PCR characterization of 11 cases showed four MLL self-fusions, four MLL-AF6, two MLL-AF9, including a novel AF9 breakpoint, and one uncharacterized t(11:19). Only 5 of 10 MLL-rearranged cases tested demonstrated karyotypic 11q23 abnormalities. FISH analysis of nine cases with an MLL-specific yeast artificial chromosome (YAC) confirmed the cytogenetic abnormalities in two cases, clarified them in one, and did not detect six cases, including three MLL self-fusions, one case with a probable MLL-rearranged subclone not represented karyotypically, and twoMLL-AF6. A whole chromosome 11 paint detected one of these MLL-AF6, and an AF6 cosmid demonstrated that the other was probably due to insertion of a submicroscopic portion of chromosome 6, including part of AF6, into an apparently normal chromosome 11. We conclude that MLL rearrangements are common in adult AML M1, that MLL self-fusion and MLL-AF6 are the most frequent types of abnormalities, and that RT-PCR is preferable to 11q23 FISH analysis for their characterization.

Adult↗