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Biomedical subjects

J Lebeau

Publications and source records attributed to J Lebeau.

At least 19 recordsLinked to original sources

Cadmium-induced apoptosis in lymphoblastoid cell line: involvement of caspase-dependent and -independent pathways.

Cadmium is a widely used heavy metal that causes severe damage to many organs including liver, kidney and lung. Cadmium toxicity has been described as in vitro and in vivo apoptosis but its molecular mechanisms are not fully understood. In this study, we used the human lymphoblastoid cell line Boleth to characterise cadmium-induced apoptosis further, using sub-lethal (10 microM) and lethal (IC50: 350 microM) doses. At lethal concentration, we observed features of apoptosis between 6 and 8 h after treatment: maturation of caspases 3 and 8, poly(ADP-ribose)polymerase (PARP) cleavage and DNA fragmentation. In order to determine the role of the MAPKs in this process, we investigated p38, ERK1/2 and c-Jun NH2-terminal kinases (JNK) phosphorylation: at lethal concentration, all these pathways were rapidly activated, but no decrease in the apoptotic rate was seen on inhibition of these kinases with drugs. Chemical inhibitors of caspases 3 and 8 blocked cleavage of PARP but not cell death, suggesting the existence of a caspase-independent death. We found that cadmium depolarised membrane potential in less than 1 h, as determined with DiOC6 dye. Interestingly, mitochondrial alteration led to the translocation of apoptosis-inducing factor (AIF) to the nucleus, where we observed chromatin condensation and possibly DNA fragmentation. These results suggest that cadmium-induced apoptosis can occur in the Boleth cell line through caspase-dependent and -independent pathways, independently of activation of major MAPKs.

Apoptosis↗

[Replantation of traumatic amputated ears by Mladick procedure: 6 cases].

UNLABELLED: Traumatic ear amputations are relatively rare. Whenever possible, ear reimplantation should be attempted, however the choice of the surgical procedure must be judicious. PATIENTS AND METHODS: We present 6 cases of partial ear amputation treated by the pocket technique described by Mladick. The series comprises 5 partial amputations severing less than half of the auricule and 1 subtotal amputation preserving the ear lobule. RESULTS: Necrosis of the avulsed fragment occurred in the only case of subtotal amputation. In the 5 other cases the revascularisation of the severed part was successful. Morphological results are often very good when the ear is freed from the pocket before 4 weeks. Beyond this delay skin grafting is necessary and inaesthetic scar retraction occurs. CONCLUSION: The success rate depends on the size and the degree of contusion of the amputated ear. We recommend the Mladick's procedure for reimplantation of fragments less than 1/2 of the auricle with favorable tissue condition. We believe that other procedures described in the literature could offer a good alternative for amputations exceeding half of the ear pavilion.

Adolescent↗

[Facial injuries treated in the Grenoble University Hospital. Epidemiological analysis of 961 patients managed in one year].

INTRODUCTION: The purpose of this study was to determine the types of facial injuries treated in a one-year in a maxillo-facial unit operating in a mountainous region. METHODS: All patients admitted to the Grenoble University Hospital maxillo-facial unit for a one year period were studied. We noted cause of trauma, age, sex, type and location of fracture, type of soft tissue injury, time between trauma and surgery. RESULTS: A total of 994 patients presenting maxillo-facial trauma underwent surgery over one year; 30% of the unit's maxillo-facial surgical activity. On average, 80 patients were treated for maxillo-facial trauma per month, with a peak of 97 facial injuries in July; 65.6% were hospitalized in the maxillo-facial unit; 25,4% of the injured were aged between 21 and 30 years. Sex-ratio was 2.7M/1F. The most frequent cause was sports injuries (25.8%) followed, in decreasing order, by traffic injuries (23.1%), home injuries (17.6%), fight injuries (3.4%), work injuries (3.4%) and dog bites (3.2%). 10.5% of the injuries occurred in a mountainous setting and 40.7% were sports injuries, 95% of which during practice of winter's sports. Injuries included facial fractures (65.5%) with or without soft tissue damage, and soft tissue injuries only (34.5%); 33.6% of the patients had other lesions of the body. 67.2% underwent surgery within the first 24 hours and 86.9% before the fifth day. DISCUSSION: Sports accidents are the leading cause of facial trauma in the mountainous regions. Most facial injuries result from ski, surf and other winter sports accidents. Most of the victims were given surgical care within the first 24 hours following the accident.

Accidents, Home↗

[Osteonecrosis of the jaws associated with bisphosphonates: five cases].

INTRODUCTION: Bisphosphonates have been recently associated with bone necrosis of jaws. PATIENTS AND METHOD: Five patients were treated, two males and three females. All patients received bisphophonates and chemotherapeutic agents, two for multiple myeloma and three for breast cancer with bone metastasis. Bisphophonates were discontinued. None of the patients had received radiotherapy to the head and neck. The localization was mandibular in four patients and the maxillary area in one with oro-antral fistula. Histological and microbiological studies were performed. RESULTS: Histopathology demonstrated osteonecrosis and ruled out detectable neoplastic disease of the jaws. Four biopsies showed Actinomycosis. Four patients underwent sequestrectomy, but the mucosa did not heal. DISCUSSION: Two mechanisms are involved: the antiangiogenic effect of bisphophonates has recently been described in vivo; as bone mineralization increases, accumulation of microdamage is observed in animals studies. Only the jaws are affected by bone necrosis, suggesting a possible trophism for bisphosphonate uptake? Other risks factors have been found: cancer, use of chemotherapeutic agents or corticosteroids, renal failure, Actinomycosis infection. The only effective treatment is dental prevention before starting treatment.

Actinomycosis, Cervicofacial↗

Submandibular gland endoscopic resection: a cadaveric study.

Recent advancement of head and neck surgery has been marked by the development of endoscopic and video-assisted minimally invasive surgery. This study reports the feasibility of endoscopic submandibular gland resection in human cadavers. Twelve submandibular gland resections were performed in six human cadavers. A 30 degrees angle endoscope and conventional surgical instruments were inserted through two 15 mm submandibular incisions. Dissection was carried out bluntly with scissors in an avascular plane superficial to the gland. No insufflation was needed since transcutaneous sutures lead to effective retraction. Facial vessels, the lingual nerve and Wharton's duct were identified and protected. Vascular ligatures were performed using surgical miniclips. After the procedure, an open submandibular dissection was performed to control the integrity of the anatomical structures. In all cases, the resection of the submandibular gland was successful without the need for an additional incision. Injuries of the facial artery and lingual nerve occurred when the procedure was carried out initially. The operative time decreased with training, from 120 min for the first cases to 35 min for the later ones. In conclusion, endoscopic submandibular gland resection is possible without major difficulty. Training and experience reduce the operative time and the complication rate.

Aged↗

[Dacryo-cysto-rhinostomy via an external approach].

The dacryo-cysto-rhinostomy via the external approach is indicated for obstruction of the lacrymal duct. It consists in the creation of short-circuit between the lacrymal sac and the external nasal wall. The operation stages starts by paracanthal incision, the subperiosteal dissection stops anteriorly to the posterior insertion of the medial canthal ligament (to preserve lacrymal function). An ostectomy is performed between the maxillary bone and the unguis. A stomy is created by individualizing two mucosal flaps. The bicanaliculonasal intubation is systematic and maintained for 10 to 12 weeks.

Dacryocystorhinostomy↗

[Beyond the lips. Reconstructive techniques and indications].

Labial tissue defects that extend beyond the anatomic boundary of the labial region confront us with two distinct reconstructive problems. When the extension is centrifugal towards the periphery, the tissue loss is essentially tegumentary. The reconstructive aim in this case is not only to restore tissues of the perilabial areas with the best possible morphologic and functional harmony but also to place the reconstructed lip harmoniously and in good relation to these structures. In the case of posterior extension of tissue losses towards the jaws, it is mandatory to reconstruct the underlying bony and eventually alveolo-dental architecture prior to the lip reconstruction. The reconstruction strategy is emphasised by two cases of complex ballistic injury.

Humans↗

Di-tert-butylhydroxylated flavonoids protect endothelial cells against oxidized LDL-induced cytotoxicity.

The protective effect of di-tert-butylhydroxylated flavonoids (chalcones and arylidenes) against minimally oxidized LDL (mO-LDL)-induced cytotoxicity was studied in cultured bovine aortic endothelial cells. Most of the tested compounds decreased aldehydes formation in medium containing mO-LDL, but their capacity to inhibit LDL oxidation in the cellular medium was not sufficient to totally reduce the cellular toxicity of mO-LDL. Most of the tested flavonoids improved the integrity of cells exposed to mO-LDL, whereas butylated hydroxytoluene was ineffective and quercetin worsened the toxicity of mO-LDL. Moreover these flavonoids induced an increase in GSH cellular levels and their protective effects might be because of their inability to reduce metal ion. Arylidene 6 substituted at position 7 by a hydroxyl group was the most potent compound.

Adenosine Triphosphate↗

[Mandibular growth, its environmental interactions].

A thorough knowledge of mandibular growth is necessary for proper comprehension of growth disorders and malformations affecting the lateral cranio-facial region. The growth mechanisms are complex and multifactorial, the mandible itself is subdivided into two heterogeneous and interdependent segments, as far as growth is concerned. These are the ramus and the corpus. The ramus is interacting with the middle cranial base through the TMJ and the temporo-pterygoid muscle belt. The mandibular body is interacting with the maxilla and the anterior cranial base. Its occlusal role is a function of the adaptive capacity of the alveolodental region.

Alveolar Process↗

[Morphological alterations of oto-mandibular syndromes].

Otomandibular dysplasia is a congenital malformation defined by a certain degree of temporomandibular or pterygomandibular hypoplasia. The syndrome is characterised by the variability of clinical findings, but the three major features are auricular, mandibular and maxillary hypoplasia. All the laterofacial structures may be affected. The deformity is usually unilateral but bilateral cases exist; a lot of associated malformations have been described. Multiple classification systems have been published. Some of them are very complex, but it is possible to define a simple diagnostic diagram based on ethiopathogenic data. Bilateral involvement affects predominantly the zygoma, and concerns hereditary syndromes. When the mandibular hypoplasia is evident Franceschetti or Goldenhar syndrome is suspected; otherwise Treacher-Collins syndrome is probable. Unilateral cases are not, in general, hereditary and the hypoplasia predominates on the mandible. The difference between hemifacial microsomia or mandibular dysplasia is made by the presence of associated laterofacial deformities.

Ear, External↗

Apoptosis inhibition mediated by medroxyprogesterone acetate treatment of breast cancer cell lines.

Several reports suggested that steroidogenic hormones could be directly involved in the regulation of apoptosis in vitro, but whether this is due to blocking or promoting mechanism of these hormones remains controversial. However, it was shown that progesterone exhibited a protective effect against the apoptotic process during mouse mammary gland involution in vivo. In this study, we analyzed the effect of medroxyprogesterone acetate (MPA) treatment, an agonist of progesterone, on serum starvation induced apoptosis on breast cancer cell lines. Positive and negative progesterone receptor (PgR+ and PgR-) breast cancer cell lines were treated with MPA (10 nM), either in standard culture conditions or in serum-free medium to induce apoptosis. Cell survival, proliferation and apoptosis were simultaneously analyzed with the expression of apoptosis-related genes measured by a real time quantitative RT-PCR. At non cytotoxic doses, MPA protected PgR+ T47-D, MCF-7 and H466-B cell lines against serum depletion-induced apoptosis, while MPA did not protect PgR-MDA-MB-231 cells against serum depletion induced apoptosis. In PgR+ cell lines and in concordance with the protective effect, the pro-apoptotic HRK and BAK1 mRNAs were up-regulated after apoptosis induction, while they were no more induced in condition of protection against apoptosis after MPA treatment. We also observed, specifically in PgR+ cells, an up-regulation of BCLX-L and BCLX-S and a down-regulation of BCL2 mRNAs, which are specific to the MPA response and unrelated to apoptotic process. Involvement of these genes with regard to the MPA-mediated protection against apoptosis is discussed.

Antineoplastic Agents, Hormonal↗

DNA damage-related RNA expression to assess individual sensitivity to ionizing radiation.

Predictive markers of intrinsic radiosensitivity in healthy individuals are needed in monitoring their occupational or environmental radiation exposure and may predict a patient's response to radiotherapy. Ionizing radiation can induce a large spectrum of DNA lesions, but under optimal DNA repair conditions, the principal residual lesions of importance are misrepaired double-strand breaks. The micronucleus (MN) assay represents a useful test in measuring radiosensitivity since it reflects non-repaired DNA breaks at the time of cell division. Spontaneous and radiation-induced MN vary greatly between individuals, and little is known about the molecular mechanisms of this variability. DNA repair and apoptosis processes are involved in the cellular response to radiation-induced DNA damage, and variation in gene expression related to these cellular pathways could be linked to individual radiosensitivity. In this study we analysed by real-time quantitative RT-PCR the basal expression of 12 genes involved both in DNA repair and apoptosis in a series of blood samples obtained from 32 healthy male donors. Relationships between basal RNA expressions and MN frequency and distribution per bi-nucleated cell were studied after ex vivo irradiation of total blood samples. Our results indicate that the variability of mRNA gene expression among the 32 subjects appears to be of the same magnitude or higher than that found for spontaneous or radiation-induced MN frequency and that RAD51 gene expression is negatively correlated with radiation-induced MN frequency.

DNA Damage↗

[Bilateral labio-maxillo-palatal clefts. Therapeutic evaluation].

The wide diversity of bilateral facial clefts makes it most difficult to assess surgical success, particularly in terms of long-term outcome. The aim of this work was to examine the rationale for the current protocol used for cleft surgery at the Grenoble University Hospital. In a first group of 28 children, a 3-step surgical protocol was applied. The first two steps were performed between 4 and 8 months with at least 3 months between each procedure. Skoog's unilateral cheilo-rhino-uranoplasty was used, associated with a periosteal tibial graft. The third step, performed between 10 and 12 months, was for staphylorraphy. Outcome was analyzed at 15 years and evidenced the deleterious effect of excessive and asymmetrical premaxillary scars, of the 2-step cheiloplasty and of columella lengthenings from the lip. The frequency of secondary revision of the superior labial vestibule and the medial labial tubercule (43%) was considered to be high; this procedure should be re-examined as should be osteotomy (32% revision). Palatine closure, acquired in 82% of the cases and premaxillary stability, achieved in 86%, would appear to favor use of the periosteal tibial graft. The osteogenic capacity of this graft tissue was less satisfactory after a second harvesting (from the same tibia three months later). These results have led us to modify our protocol, favoring early and total closure of the bony palate and continued use of the periosteal tibial graft. We now use the following operative protocol: premaxillary alignment using an active orthopedic plate at 2 months, lip adhesion associated with staphylorraphy and passive palatine contention plate at 3 months, definitive bilateral cheilo-uranoplasty associated with a single periosteal graft at 7 months. The preliminary results with this protocol in a group of 12 children have shown better quality scars, more harmonious maxillary arches, an excellent occlusion of the deciduous dentition, and preservation of the positive results obtained with the periosteal tibial graft.

Adolescent↗