Bacillus sp.: A Remarkable Source of Bioactive Lipopeptides.

Surfactin, one of the best lipopeptide surfactants, was first isolated from Bacillus sp. in 1969. Since then, Bacillus sp. has been a remarkable source of bioactive lipopeptides, with a huge natural biodiversity. Lipopeptides from Bacillus sp. are now divided into three main families: surfactin, fengycin, and iturin. The peptide moiety of these lipopeptides is synthesised by huge multi-enzymatic proteins called nonribosomal peptide synthetases, which are responsible for the peptide biodiversity of these lipopeptides. Moreover, the fatty acid chain also encompasses a high diversity with different ß-hydroxy or ß-amino fatty acid chains of different lengths, isomery, or saturation, which can be incorporated. After describing the mode of synthesis of the different families of lipopeptides produced by Bacillus sp. and their biodiversity, this chapter describes how this lipopeptide biodiversity can be increased using genetic engineering and how the lipopeptides can be overproduced and purified. The high biodiversity of lipopeptides induces a broad range of physicochemical properties, which can be linked to multiple biological activities with many applications in different sectors. The increasing understanding of the mode of biosynthesis of these lipopeptides should lead to the development of novel compounds with increased properties and applications.

[Malakoplakia of the submandibular gland in a renal transplant patient]. / Malakoplakie de la glande sous-mandibulaire chez un patient transplanté rénal.

INTRODUCTION: Malakoplakia (MP) is a rare granulomatous disease, usually occurring in immunocompromised patients, linked to Escherichia coli infection. The lesions are usually located in the genitourinary tract, but there is a great variability in the topography and the clinical presentation. CASE REPORT: A 70-year-old diabetic kidney transplant patient under immunosuppressive treatment presented with a voluminous submandibular chronic lesion, involving the skin, associated with a burgeoning lesion of the oral mucosa. Histological examination of biopsies concluded to MP and bacteriological samples were positive for E. coli. Antibiotic treatment allowed for the regression of the lesion before surgical removal. Histological examination of resected material confirmed the diagnosis of invasive MP of the submandibular gland. DISCUSSION: The diagnosis of MP relies on histological examination, showing the presence of von Hansemann's cells and Michaelis- Gutmann bodies. The treatment is based on active antibiotics targeted against intracellular bacteria, possibly associated with surgery. We report the first case of MP involving the submandibular gland.

[Antisynthetase syndrome and lung carcinoma: a fortuitous association?]. / Syndrome des antisynthétases et adénocarcinome pulmonaire: une association fortuite?

INTRODUCTION: Dermatomyositis and polymyositis are sometimes associated with neoplasia. Conversely, a link between antisynthetase syndrome and neoplasia has not been clearly demonstrated. CASE REPORT: We report a 54-year-old smoker male patient who presented with an antisynthetase syndrome with anti-Jo1 and anti-Ro-52 antibodies. An adenocarcinoma of the lung was diagnosed at the same time. CONCLUSION: Two recent studies showed that patients with an antisynthetase syndrome associated with anti-Jo1 antibodies have more severe prognosis than antisynthetase syndrome associated with other antibodies (i.e. PL7/PL12). The risk of cancer occurrence seems to be increased when the anti-Jo1 antisynthetase syndrome is associated with anti-Ro-52 antibodies. To date, there is no demonstrated association between antisynthetase syndrome and neoplasia.

[Recommendations for pediatric oxygen therapy in acute and chronic settings: Needs assessment, implementation criteria, prescription practices and follow-up]. / Recommandations pour l'oxygénothérapie chez l'enfant en situations aiguës et chroniques : évaluation du besoin, critères de mise en route, modalités de prescriptions et de surveillance.

Recommendations for acute and long-term oxygen therapy (needs assessment, implementation criteria, prescription practices, and follow-up) in children were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP2A). The Haute Autorité de Santé (HAS) methodology, based on the Formalized Consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text (arguments+recommendations) is available at the website of the French Paediatric Society: www.sfpediatrie.com.

[Recommendations for pediatric oxygen therapy in acute and chronic settings: needs assessment, implementation criteria, prescription practices and follow-up]. / Recommandations pour l'oxygénothérapie chez l'enfant en situations aiguës et chroniques : évaluation du besoin, critères de mise en route, modalités de prescription et de surveillance.

Recommendations for acute and long-term oxygen therapy (needs assessment, implementation criteria, prescription practices, and follow-up) in children were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP2A). The Haute Autorité de Santé (HAS) methodology, based on the Formalized Consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text (arguments+recommendations) is available at the website of the French Paediatric Society: www.sfpediatrie.com.

[Jaw osteonecrosis induced by oral biphosphonates: 12 cases]. / Ostéonécroses des mâchoires induites par les biphosphonates oraux: 12 cas.

INTRODUCTION: The incidence of jaw osteonecrosis induced by oral or intravenous biphosphonates (BP) has been increasing. Two hundred cases of jaw osteonecrosis induced by oral BP (JONOBP) were reported, with an incidence of 4 % and a prevalence of 1/952. We report 12 cases of JONOBP observed from January 2007 to January 2009. MATERIAL AND METHODS: A pluridisciplinary committee including odontologists, stomatologists, and maxillofacial surgeons from two Paris hospitals was asked to manage patients treated by BP. Twelve patients presenting with JONOBP were included from January 2007 to January 2009. For each of these patients, age, sex, associated co-morbidities, any triggering factor, previous or current combination treatments, the type of BP used, its initial indication, dosage, delay before onset of JONOBP, and delay between first clinical signs and diagnosis were studied. JONOBP localization, stage (American Association of Oral and Maxillofacial Surgeons [AAOMS] classification), clinical and radiological signs, anatomopathological and bacteriological examinations (when performed) were documented. The treatment and evolution were described. RESULTS: Ten women and two men, mean age 65 years (36 to 82 years), were included. BP were taken orally once a week or daily. The mean duration of BP exposure was 39.6±2,4 months (19 to 58 months). The indication for BP was prevention or treatment of osteoporosis in 11 cases and breast with bone metastases in one case. Tooth extraction was the triggering factor in nine cases. The premolar and molar mandibular area was the most often affected. Corticosteroid therapy was combined to BP in half of the cases. There were no clinical, radiological, and histological specific signs. BP treatment was stopped in all patients. Nine patients underwent surgery. Evolution was favorable for nine patients. Six patients were cured, on average 3.8 months after beginning management (one to nine months). Three male patients improved. Three female patients were lost to follow-up. Alendronate was the most frequently implicated (six cases) and risedronate (five cases). Five patients presented with diagnosed or suspected auto-immune conditions. DISCUSSION: The duration of exposure to BP was superior to three years in most cases. The triggering factor was tooth extraction. The mean diagnostic delay was five months. There were more stage 2 and 3 patients, according to the AAOMS classification. They were the most frequent, probably because of the higher number of co-morbidities, especially corticosteroid intake. Patient management complied to Afssaps and AAOMS recommendations. The evolution was favorable for all managed patients.

[Mandibular fractures: epidemiology, therapeutic management, and complications in a series of 563 cases]. / Fractures de la mandibule: épidémiologie, prise en charge thérapeutique et complications d'une série de 563 cas.

INTRODUCTION: The Paris urban and suburban area (Ile-de-France) has the leading regional population in France. This population has specific characteristics. This study concerns mandibular fractures. MATERIAL AND METHOD: A retrospective epidemiologic, clinical, radiographical and therapeutic analysis is conducted with a series of 563 patients with mandibular fracture treated at the Pitié-Salpêtrière University Hospital, in Paris, from 1998 to 2000. RESULTS: Mandibular fracture was generally observed in young men, 40% of whom had poor oral hygiene. The brawls were the dominant etiology (57%) followed by road accidents (12%). The most frequent unifocal fractures were condylar fractures (32%) and angle fractures (32%). The most frequent bifocal mandibular fracture associated angle and symphysis fractures (32%). Osteosynthesis was performed for 73% of patients, including 30% with associated maxillary locking. Complications occurred in 4.8% of the studied cases. DISCUSSION: Despite the increase in traffic, the incidence of road injuries has declined. The first leading and progressing cause of mandibular fractures is brawls. Surgical treatment generally consists in fixation of the bone fracture. Maxillary locking is still associated in 33% of patients, but with a 50% shorter duration. Complications routinely arise because of poor bad oral hygiene.

Endoscopic excision of forehead lipomas.

Endoscopic surgery is a significant addition in the maxillofacial surgeon's armamentarium. Authors' experience of endoscopically assisted removal of forehead lipomas has been presented. The endoscopic technique permits to hide minimal scars in the hair. The magnification allows a good identification of anatomical structures and thus decreases the risk of numbness. The main disadvantages of this technique are the more expensive equipment and the steep learning curve. But with the expansion of endoscopic techniques, prices should decline and the duration of operations always lessens with experience. This technique might possibly appear to offer a new standard procedure for removal of forehead lipomas, notably in patients with keloid history or high aesthetic concerns.

[Endoscopically assisted retro-caroncular approach for medial wall fracture of the orbit: preliminary study]. / La voie d'abord rétro-caronculaire assistée par endoscopie pour le traitement des fractures de la paroi interne de l'orbite: étude préliminaire.

PURPOSE: The purpose of this study was to present our experience of endoscopically assisted retro-caruncular approach of medial wall fracture of orbital bone, notably concerning the accessibility and visibility. METHODS: Five consecutive patients (4 men and 1 woman) with recent fracture (1 to 3 days), underwent medial wall reconstruction with a polydioxanone plate, endoscopically assisted via a retro-caruncular approach. The surgical technique and its results are described. Helpful hints are discussed. RESULTS: The plate did not have to be bent for introduction. Operative time was less than an hour for all patients. All patients were discharged the day after surgery. All experienced a mild degree of postoperative edema-related diplopia. None had persistent or secondary diplopia or enophthalmos at the one and six-month follow-up visits, respectively. Other postoperative complications, such as hematoma, nerve injury, or infection were not observed. All patients were satisfied with the outcome and especially the cosmetic result. DISCUSSION: The retro-caruncular approach with adjunctive endoscopic surgery should be the gold standard for posttraumatic isolated medial wall reconstruction of the orbit.

Genetic heterogeneity of the hypervariable region I of Hepatitis C virus and lymphoproliferative disorders.

B-cell lymphoproliferative disorders (BCLD) have been associated with chronic hepatitis C virus (HCV) infection. The HCV glycoprotein E2 (gpE2) hypervariable region I (HVR-I) may be a potential antigenic candidate to promote B-cell proliferation. The purpose of this study was to analyze the influence of HVR-I sequence variability in the development of BCLD. HVR-I sequences were studied in 29 chronically HCV-infected patients with (n=15) or without (n=14) BCLD. After PCR amplification of the gpE2 region, analysis of the 81 bp HVR-I encoding fragment was performed on 7-18 clones per patient. HVR-I sequence complexity was slightly lower in patients with BCLD (mean 0.347) than without (0.468) (P=0.2), though, sequence diversities were similar (0.0370 vs 0.0954, P=0.239). Phylogenetic analysis did not reveal any BCLD-associated clustering. In our population, neither the recently described insertion between positions 1 and 2 of HVR-I nor residues at positions 4 and 13 were particularly linked to BCLD. As previously described, we confirm the high degree of conservation of HVR-I residues T-2, G-6 and G-23 in our patients. Contrary to recent findings, our analysis based on multiple clones per patient analysis did not reveal any particular motif associated with BCLD.

[Epidemiological features and incidence trends of primary cerebral lymphomas observed in 80 HIV-infected patients from 1983 to 1999]. / Caractéristiques épidémiologiques et évolution de l'incidence des lymphomes cérébraux primitifs observés chez 80 patients infectés par le VIH entre 1983 et 1999.

OBJECTIVE: To describe the epidemiological characteristics of primary central nervous system lymphoma (PCNSL) and the evolution of the incidence of this lymphoma in HIV-infected patients with a more than 17-year follow-up. RESULTS: Eighty cases of PCNSL were analyzed from a data base of 2,263 AIDS subjects followed from 1983 to 1999 (3.5% of the patients with AIDS). At the time of diagnosis, PCNSL was the first AIDS defining event in 36% of the cases, median CD4 count was 9/mm3 (0-134); 82% of the patients were given antiretroviral therapy (HAART = 0). Only eight cases of PCNSL were observed after 1996 (median HIV RNA level: 250,000 copies/mL (24,000-1,500,000)). The incidence was 39 per 100 patients-year in 1991 and decreased to 1.9 in 1999. At the end of the study, 78 patients had died (98%). The median survival was one month before 1996 ([0-27], n = 72), and was ten months after ([0-44], n = 8). Two patients were still alive 38 and 44 months after diagnosis. After 1996, survival was increased in patients with good response to antiretroviral treatment and in patients with high CD4 count at the moment of diagnosis. CONCLUSION: After the introduction of HAART (1996), the incidence of PCNSL has decreased drastically and survival was increased.

Ergotism related to a single dose of ergotamine tartrate in an AIDS patient treated with ritonavir.

We report a rare case of ergotism related to a single dose of ergotamine tartrate in a man with AIDS being treated with ritonavir. He was treated with a prostacyclin analogue and made a complete recovery.

HIV combination therapy: immune restitution causing cryptococcal lymphadenitis dramatically improved by anti-inflammatory therapy.

Two patients with AIDS developed microscopically verified focal cryptococcal lymphadenitis while treated with highly active anti-retroviral therapy for 8 and 15 months. Both were treated with fluconazole as a secondary prophylaxis for prior cryptococcal meningitis. Cryptococcus neoformans did not grow. Amphotericin was ineffective. Anti-inflammatory drugs had a dramatic effect.

The acidic activation domain of the Epstein-Barr virus transcription factor R interacts in vitro with both TBP and TFIIB and is cell-specifically potentiated by a proline-rich region.

In cells latently infected with Epstein-Barr virus (EBV), the expression of two viral transactivators, EB1 and R, is responsible for the switch from latency to a productive cycle. R contains a DNA-binding/dimerization domain localized at the N-terminus. The domain required for transcriptional activation is localized at the C-terminus and contains two regions of very different amino acid composition. The first is very rich in prolines, whereas the second is rich in acidic residues and contains two potential alpha-helices. We investigated the activation potential of these subregions when linked to the heterologous Gal4 DNA-binding domain. We found that the acidic region--more precisely, the second putative alpha-helix--is an activating domain. In contrast, the proline-rich region is insufficient by itself for activation but collaborates with the acidic region in a cell-specific manner to make transactivation more efficient. We demonstrated that R interacts in vitro with the basal transcription factors TBP and TFIIB, and that the acidic domain of R mediates these interactions.

Domains of the Epstein-Barr virus (EBV) transcription factor R required for dimerization, DNA binding and activation.

In cells latently infected with EBV, the switch from latency to a productive infection is linked to the expression of two transcriptional activators, the upstream element factor EB1 and the enhancer factor R. R activates by interacting directly with specific DNA sequences called RREs (R Responsive Elements). Each binding site covers about 18 bp, where R simultaneously contacts two core sequences separated by 5 to 7 bp (1). Here we show that R binds in vitro as a homodimer to an RRE, and that stable homodimers can also form in solution in the absence of DNA. By functional analysis of deletion and insertion mutants of R, we have localized the DNA binding region within the 280 N-terminal amino acids and the dimerization region within the 232 N-terminal amino acids. As no obvious homologies were detected with other known DNA binding or dimerization motifs, R could contain novel protein structures mediating these functions. The transcriptional activation domain has been located in the C-terminal half of the protein. This domain contains two regions with structures already identified in other transcription factors: one region is rich in proline, the other rich in acidic residues.

The enhancer factor R of Epstein-Barr virus (EBV) is a sequence-specific DNA binding protein.

In cells latently infected with EBV, the switch from latency to productive infection is linked to the expression of two EBV transcription factors called EB1 (or Z) and R. EB1 is an upstream element factor which has partial homology to the AP1/ATF family, whereas R is an enhancer factor. In the R-responsive enhancer of the replication origin only active during the EBV lytic cycle (ORIIyt), R-responsive elements are located in a region of about 70 bp (RRE-DR). Here we show that R, produced either by in vitro translation, or present in nuclear extracts from HeLa cells constitutively producing R, binds directly to and protects against DNAase I digestion, two regions in RRE-DR. Using mobility shift assay and DMS interference, we have characterized the contact-points between R and the DNA. Two binding sites, RRE-DR1 and RRE-DR2, were characterized and are contiguous in RRE-DR. R binds to these two sites probably by simultaneously contacting two sequences within the sites, which are separated by 7 bp in RRE-DR1, cctGTGCCttgtcccGTGGACaatgtccc, and by 6bp in RRE-DR2, caatGTCCCtccagcGTGGTGgctg. Direct interaction of R with its cognate sequences is conferred by its N-terminal 355 amino-acids. Directed mutagenesis in RRE-DR, of either R-binding site, impaired binding of R in vitro and, as assayed by transient expression in HeLa cells, impaired R-activation by a factor of two. This suggests that RRE-DR1 and RRE-DR2 do not respond cooperatively to R.