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Biomedical subjects

F Bernard

Publications and source records attributed to F Bernard.

At least 19 recordsLinked to original sources

Notch pathway repression by vestigial is required to promote indirect flight muscle differentiation in Drosophila melanogaster.

Drosophila dorsal longitudinal muscles develop during metamorphosis by fusion of myoblasts with larval templates. It has been shown that both vestigial and Notch are crucial for correct formation of these muscles. We investigated the relationship between vestigial and the Notch pathway during this process. Using Enhancer of Split Region Transcript m6 gene expression as a reporter of Notch pathway activity, we were able to demonstrate that this pathway is only active in myoblasts. Moreover, close examination of the cellular location of several of the main actors of the N pathway (Notch, Delta, neuralized, Serrate, Mind bomb1 and fringe) during dorsal longitudinal muscle development enabled us to find that Notch receptor can play multiple roles in adult myogenesis. We report that the locations of the two Notch ligands (Delta and Serrate) are different. Interestingly, we found that fringe, which encodes a glycosyltransferase that modifies the affinity of the Notch receptor for its ligands, is expressed in muscle fibers and in a subset of myoblasts. In addition, we demonstrate that fringe expression is essential for Notch pathway inhibition and muscle differentiation. Lastly, we report that, in vestigial mutants, fringe expression is lost, and when fringe is overexpressed, a significant rescue of indirect flight muscle degeneration is obtained. Altogether, our data show that a vestigial-differentiating function is achieved through the inhibition of the Notch pathway.

Animals↗

[Myocardial bridging and coronary spasm on effort].

The discovery of myocardial bridging during coronary angiographies is common. Yet these bridges are rarely the origin of acute coronary syndrome. We report the case of an active 45 year old man with no cardiovascular risk factors who had acute coronary syndrome. Emergency coronary angiography just revealed two myocardial bridges on the anterior interventricular artery which did not explain this acute episode. A subsequent second angiogram together with endocoronary echography demonstrated that there was no atheroma and a methergin test set off diffuse coronary spasm. The association of myocardial bridging and coronary spasm has only rarely been reported in the literature. We describe the clinical, therapeutic and prognostic characteristics.

Angina, Unstable↗

Incidence of adrenal insufficiency after severe traumatic brain injury varies according to definition used: clinical implications.

BACKGROUND: Adrenal insufficiency impacts on the haemodynamic management of patients in intensive care. Very little is known about the incidence of adrenal insufficiency in the first 10 days after traumatic brain injury. METHODS: We retrospectively reviewed the charts of 113 traumatic brain injury patients within 10 days of their injury. They all had a high-dose corticotropin stimulation test performed because of haemodynamic instability. Blood cortisol concentrations were measured at baseline, 30 and 60 min after the administration of high-dose corticotropin. The incidence of adrenal insufficiency was determined according to various definitions used in the literature. RESULTS: The baseline cortisol concentration was <414 nmol litre(-1) (15 microg dl(-1)) in 78% of patients and <690 nmol litre(-1) (25 microg dl(-1)) in all patients. The cortisol concentration did not rise above 500 nmol litre(-1) (18 microg dl(-1)) at 30 and 60 min in 49 and 22% of patients, respectively. The cortisol concentration did not rise by 250 nmol litre(-1) (9 microg dl(-1)) at 30 and 60 min in 48 and 25% of patients respectively. Primary adrenal insufficiency defined by an abnormal baseline cortisol concentration and an abnormal response to the high-dose corticotropin stimulation test was present in 13-28% of patients according to the cut-off values used. CONCLUSIONS: The incidence of adrenal insufficiency varies from 25 to 100% in the first 10 days after traumatic brain injury. The range of incidences reported illustrates the need for standardization of the definition of adrenal insufficiency. This has a direct impact on treatment. Sampling at 60 min after the high-dose corticotropin stimulation test seems to correlate better with the maximum secreting capacity of the adrenal glands.

Adolescent↗

A role for betaFTZ-F1 in regulating ecdysteroid titers during post-embryonic development in Drosophila melanogaster.

Variations in ecdysteroid titers play crucial roles in arthropods by initiating and regulating molting and metamorphosis. The recent identification of genes coding for cytochrome P450 enzymes involved in Drosophila ecdysteroidogenesis provides new molecular tools to investigate the regulation of insect hormone production. In the present study, we used an enzyme immunoassay to show that the molting hormone titer is strictly correlated with the steroidogenic capacity of the ring gland. A temporal correlation between dynamics of ecdysone production and expression of genes encoding steroidogenic enzymes was observed during the third instar, suggesting that the timing of hormone production depends on transcriptional regulation of the biosynthetic enzymes. Using clonal analysis, levels of two steroidogenic enzymes, Phantom (PHM) and Disembodied (DIB), were shown to be very reduced in ftz transcription factor 1 (ftz-f1) mutant ring gland cells whereas there was no effect of the without children (woc) mutation, suggesting that FTZ-F1 regulates phm and dib expression. Since betaFTZ-F1 is the homolog of the vertebrate steroidogenic factor 1 (SF1), which plays a key role in the differentiation of vertebrate steroidogenic organs through transcriptional regulation of steroidogenic enzymes, this study emphasizes the strong parallels between insects and vertebrates with respect to the regulatory mechanisms of steroidogenesis.

Animals↗

Multi-centre pilot study of 2-chlorodeoxyadenosine and cytosine arabinoside combined chemotherapy in refractory Langerhans cell histiocytosis with haematological dysfunction.

The aim of this study was to assess the efficacy and adverse effects of 2-chlorodeoxyadenosine (2-CdA) and cytosine arabinoside (Ara-C) in children with refractory Langerhans cell histiocytosis (LCH) and haematopoietic dysfunction. Ten patients, with a median age at diagnosis of 0.5 years, were enrolled in this study. Treatment comprised at least two courses of Ara-C (1000 mg/m(2)/d) and 2-CdA (9 mg/m(2)/d) administered for 5d every 4 weeks; subsequent median follow-up was 2.8 years (range 0.03-6.4 years). Among the 7 patients who received at least two courses of therapy, disease activity decreased in 6 patients, and control of disease was achieved in all patients after a median delay of 5.5 months. All patients suffered World Health Organisation (WHO) grade 4 haematological toxicity. Two septic deaths occurred shortly after administration of the first course of 2-CdA/Ara-C; a third patient was withdrawn from the trial after the first course and subsequently died following haematopoietic stem cell transplantation. This series is small, but we conclude that 2-CdA and Ara-C combined chemotherapy probably has major activity in childhood refractory Langerhans cell histiocytosis.

Antineoplastic Combined Chemotherapy Protocols↗

[Left auricle myxoma, a rare cause of myocardial infarction].

INTRODUCTION: The association of left auricle myxoma and myocardial infarction is exceptional. Nevertheless, a causal relationship exists between the 2 affections. OBSERVATION: A 54 year-old woman was hospitalised in a rush for myocardial infarction. Sonography revealed a voluminous tumoral formation in the left auricle. The diagnosis of myxoma was confirmed by the anatomopathological examination. DISCUSSION: Although systemic embolism represents the most frequent causal link between left auricle myxoma and myocardial infarction, hypercoagulability is another possible cause. This can be explained by the secretion of interleukins 6 and 8 by the myxoma.

Female↗

[BK virus infection in a child after an hematopoietic stem cell transplantation].

Polyomavirus hominis 1, better known as BK virus (BKV), infects up to 90% of the general population. Significant clinical manifestations can be seen in immunocompromised patients. We report a case of haemorragic cystitis likely due to BKV in a child after allotransplantation of hematopoietic stem cells. A 10-year old boy with poor-prognosis acute T lymphoblastic leukaemia underwent cord blood allogeneic stem cell transplantation while in his first relapse. Macroscopic haematuria and low back pain occurred by day 95, in the context of acute graft versus host disease and pulmonary aspergillosis. Histopathologic examination showed a cytopathogenetic effect consistent with the diagnosis of BKV infection. Urinary PCR was positive for BKV. Treatment with cidofovir was followed by a marked improvement of urinary symptoms. The current understanding, diagnosis, and treatment of BKV-associated infection is discussed.

Antiviral Agents↗

Molecular characterisation and ovine live vaccine 1B evaluation toward a Chlamydophila abortus strain isolated from springbok antelope abortion.

Chlamydiosis is a zoonosis with a worldwide distribution. The reservoir of susceptible hosts is large and includes birds and both domestic and wild mammals. Chlamydial infection, determined serologically, seems to be widespread among wild ruminants in the Paris zoo (France). In February 2003, an abortion case was reported within the springbok (Antidorcas marsupialis) herd of the zoo. PCR assay using primers targeting the polymorph membrane protein gene (pmp) family was performed on both vaginal swab and placenta samples revealing the presence of Chlamydophila. The inoculation into chicken embryos of an infected placenta extract led to the successful isolation of a C. abortus strain referred to as ASb1. The omp1 gene coding the major outer membrane protein (momp) and the 16S-23S rRNA spacer region of ASb1 were compared to those of various strains by restriction fragment length polymorphism (RFLP). The RFLP analysis showed that this isolate belonged to Chlamydophila abortus species and is highly related to known domestic ruminant's strains causing abortion. The efficacy of a live vaccine 1B, based on a temperature-sensitive mutant of the ovine abortion reference strain AB7, was tested. Protection-challenge experiments in a mouse model show that the ASb1 strain led to mice abortions and that vaccination with 1B vaccine provided them with effective protection.

Abortion, Veterinary↗

Efficacy of live Chlamydophila abortus vaccine 1B in protecting mice placentas and foetuses against strains of Chlamydophila pecorum isolated from cases of abortion.

The efficacy of Chlamydophila abortus vaccine strain 1B in protecting against two selected Chlamydophila pecorum strains, isolated from an aborted goat (M14) in Morocco and a ewe (AB10) in France, was investigated in a mouse model, by comparing the reduction in number of bacteria in the placentas of vaccinated mice challenged intraperitoneally at 11 days of pregnancy with the reference C. abortus (AB7) and C. pecorum (M14, or AB10) strains, to those of unvaccinated mice. Vaccine 1B was shown to provide effective protection against the field strains of C. pecorum, since it significantly reduced the placental Chlamydophila colonisation. The two C. pecorum strains were not sufficiently abortifacient in mice to use reduction in abortion as a criterion of protection.

Abortion, Veterinary↗

A new clinical score for disease activity in Langerhans cell histiocytosis.

OBJECTIVE: To develop an objective tool for assessing disease activity in patients with Langerhans cell histiocytosis (LCH). METHOD: Scoring system was developed and applied to a database containing information on 612 patients. RESULTS: At diagnosis, the score distribution was highly asymmetrical: the score was between 0 and 2 in 74% of cases, 3-6 in 16%, 7-10 in 3%, and more than 10 in 6%. The 5-year mortality rates were 1, 4.4, and 43.4%, respectively, among patients with initial scores of 0-2, 3-6, and >6. Stability or an increase of the score at 6 weeks was highly predictive of death among patients with initial scores above 6, while score stability had no significant impact on vital outcome among patients with low or moderate scores at diagnosis. CONCLUSIONS: This LCH disease activity score provides an objective tool for assessing disease severity, both at diagnosis and during follow-up and treatment.

Antineoplastic Combined Chemotherapy Protocols↗

[Prognosis of neuroblastoma in childhood. Methods of assessment and clinical use].

Neuroblastoma and its benign counterpart, ganglioneuroma, are pediatric neuroblastic tumors arising in the sympathetic nervous system from neural-crest cells. Neuroblastoma, the most common extra-cranial solid tumour during childhood, is unique for its broad spectrum of clinical virulence from spontaneous remission to rapid and fatal progression despite intensive multimodality therapy. To a large extent, outcome could be predicted by the stage of disease and the age at diagnosis. However, a number of molecular events in neuroblastoma tumors, accounting for the variability of outcome and response to therapy, have been identified over the past decades. Among these, MYCN amplification is the most relevant prognostic factor and was the first genetic marker, in paediatric oncology, to be included in clinical strategies as a guide for therapeutic decision. This has allowed the most suitable intensity of therapy to be delivered according to a risk-stratified strategy, from observation to megadose chemotherapy with stem cell transplantation. Recent advances in understanding the biology and genetics of neuroblastoma will ultimately allow to select poor-risk patients for appropriate future biologically based therapies.

Antineoplastic Combined Chemotherapy Protocols↗

Control of apterous by vestigial drives indirect flight muscle development in Drosophila.

Drosophila thoracic muscles are comprised of both direct flight muscles (DFMs) and indirect flight muscles (IFMs). The IFMs can be further subdivided into dorsolongitudinal muscles (DLMs) and dorsoventral muscles (DVMs). The correct patterning of each category of muscles requires the coordination of specific executive regulatory programs. DFM development requires key regulatory genes such as cut (ct) and apterous (ap), whereas IFM development requires vestigial (vg). Using a new vg(null) mutant, we report that a total absence of vg leads to DLM degeneration through an apoptotic process and to a total absence of DVMs in the adult. We show that vg and scalloped (sd), the only known VG transcriptional coactivator, are coexpressed during IFM development. Moreover, we observed an ectopic expression of ct and ap, two markers of DFM development, in developing IFMs of vg(null) pupae. In addition, in vg(null) adult flies, degenerating DLMs express twist (twi) ectopically. We provide evidence that ap ectopic expression can induce per se ectopic twi expression and muscle degeneration. All these data seem to indicate that, in the absence of vg, the IFM developmental program switches into the DFM developmental program. Moreover, we were able to rescue the muscle phenotype of vg(null) flies by using the activity of ap promoter to drive VG expression. Thus, vg appears to be a key regulatory gene of IFM development.

Animals↗

Malignant B cell non-Hodgkin's lymphoma of the larynx in children with Wiskott Aldrich syndrome.

A 15 years old male with a primary diagnosis of Wiskott Aldrich syndrome presented a laryngeal B cell lymphoma associated with Epstein-Barr virus. A chemotherapy and a radiotherapy were started in association with an endoscopic debulking of the tumor. The child died of respiratory failure secondary to a lung infection. The incidence of NHL (non-Hodgkin's lymphoma) of laryngeal origin in infants is extremely low and to our knowledge it has never been found in Wiskott Aldrich syndrome.

Adolescent↗

Fluorescent Pseudomonas mainly produce the dihydro form of pyoverdine at low specific growth rate.

AIMS: To analyse the influence of cell growth rate and iron concentration on the production of pyoverdines (PVDs) and of their reduced dihydro forms by three fluorescent Pseudomonas strains (P. putida BTP16, P. fluorescens BTP7 and P. aeruginosa 7NSK2). METHODS: PVD and dihydropyoverdine (DHPVD) productions were determined by LC ESI-MS and spectrophotometry during batch and chemostat culture at different dilution rates. SIGNIFICANCE: The relatively high PVD-to-DHPVD ratio (0.57) observed in pH-controlled batch cultures suggested that a base-catalysed chemical oxidation of the dihydroform is not the prime mechanism involved in generating PVDs. Interestingly, in chemostat cultures the PVD-to-DHPVD ratio was significantly reduced at low specific growth rate. Our results suggest that the oxidation of DHPVD to PVD is catalysed by an iron-dependent enzymatic reaction rather than a chemical oxidation.

Biomass↗

[Coronary dissection associated with exercise: unusual cause of myocardial infarction].

A case of coronary artery dissection occurring immediately after weight training is reported in a young adult with no cardiovascular risk factor. The patient had an anterior myocardial infarction treated by primary coronary angioplasty and stenting. Other rare but similar cases have been reported in the literature with a generally poor prognosis. The physiopathological mechanisms acting during exercise or the immediate recovery period are thought to be either trauma of the arterial wall by the myocardium itself or coronary artery spasm. Present management of this condition is based on coronary angioplasty with stenting.

Adult↗