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Biomedical subjects

F Le Gall

Publications and source records attributed to F Le Gall.

At least 37 records · Page 2Linked to original sources

Expression and phylogeny of the multiple antenna genes of the low-light-adapted strain Prochlorococcus marinus SS120 (Oxyphotobacteria).

In contrast to typical cyanobacteria, Prochlorococcus strains possess an intrinsic divinyl-chlorophyll (Chl) a/b-protein complex instead of phycobilisomes as the major light-harvesting system. These pigment-protein complexes are encoded by a variable number of pcb genes depending on the ecotype to which the Prochlorococcus strain belongs: low-light-adapted strains possess several pcb gene copies whereas only a single copy is present in high-light-adapted strains. In this study, the light-regulated expression of the seven pcb genes of Prochlorococcus marinus SS120 was examined. The pcbF gene was found to exhibit a high turnover and its mRNA could only be detected as a degraded product under all light conditions. Steady-state levels of transcripts originating from the six other pcb gene copies varied over several orders of magnitude but were not significantly differentially regulated by light intensity. Transcript levels of most pcb genes increased between 4.5 and 8.5 micromol quanta m(-2) s(-1), peaked at 45 micromol m(-2) s(-1) and decreased at the highest irradiance (72 micromol m(-2) s(-1)). A phylogenetic analysis of the Pcb proteins and other members of the six-helix Chl protein superfamily revealed that PcbC and PcbG make a separate cluster with regard to the other Pcbs from SS120. In contrast, Pcb sequences from four high-light-adapted Prochlorococcus sp. strains were found to cluster together and to be less variable than SS120 Pcbs. Thus, pcb genes likely evolved at a different rate in the two Prochlorococcus ecotypes. Their early multiplication and diversification is likely a key factor in the successful adaptation of some genotypes to very-low-light conditions.

Adaptation, Physiological↗

Of mice and men: hybridoma and recombinant antibodies.

Thousands of mouse monoclonal antibodies have been produced from hybridomas over the past 25 years. The same technique can now be used to clone human antibodies from transgenic mice. Full-length antibodies and recombinant fragments engineered for various diagnostic and therapeutic applications can be obtained in reasonably large amounts after expression in mammalian cells, milk and plants.

Animals↗

Scorpion alpha and alpha-like toxins differentially interact with sodium channels in mammalian CNS and periphery.

Scorpion alpha-toxins from Leiurus quinquestriatus hebraeus, LqhII and LqhIII, are similarly toxic to mice when administered by a subcutaneous route, but in mouse brain LqhII is 25-fold more toxic. Examination of the two toxins effects in central nervous system (CNS), peripheral preparations and expressed sodium channels revealed the basis for their differential toxicity. In rat brain synaptosomes, LqhII binds with high affinity, whereas LqhIII competes only at high concentration for LqhII-binding sites in a voltage-dependent manner. LqhII strongly inhibits sodium current inactivation of brain rBII subtype expressed in HEK293 cells, whereas LqhIII is weakly active at 2 microM, suggesting that LqhIII affects sodium channel subtypes other than rBII in the brain. In the periphery, both toxins inhibit tetrodotoxin-sensitive sodium current inactivation in dorsal root ganglion neurons, and are strongly active directly on the muscle and on expressed muI channels. Only LqhII, however, induced repetitive end-plate potentials in mouse phrenic nerve-hemidiaphragm muscle preparation by direct effect on the motor nerve. Thus, rBII and sodium channel subtypes expressed in peripheral nervous system (PNS) serve as the main targets for LqhII but are mostly not sensitive to LqhIII. Toxicity of both toxins in periphery may be attributed to the direct effect on muscle. Our data elucidate, for the first time, how different toxins affect mammalian central and peripheral excitable cells, and reveal unexpected subtype specificity of toxins that interact with receptor site 3.

Animals↗

[Human orf and erythema multiforme].

BACKGROUND: Orf is a disease of sheep due to a parapoxvirus. Transmission in man is possible, and is generally benign, self-limited condition. Although, rare complications have been mentioned. We report a case of Orf with erythema multiforme in a young girl. CASE REPORT: A 13-year-old girl presented to our department with an erythema multiform. The cutaneous examination revealed painless erythematous nodule of her right index finger developed 15 days after a contact with a lamb. The diagnosis of Orf complicated by erythema multiforme was made on the basis of her typical history. Lesions heal with symptomatic therapy in 15 days. DISCUSSION: Orf presents in sheeps as a pustular dermatitis or a vesicular oral mucosal lesions, and in man as a single lesion on the site of infection. This lesion generally heals without complications, although secondary infection is not uncommon. Twenty one cases of erythema multiforme have been recorded following infection with the Orf virus. In typical cases, the diagnosis is established by a history of contact with infected animals and the appearance of the lesion. Electron microscopic examination can be helpful sometimes. Lesions regress in 4 to 5 weeks without specific treatment.

Child↗

[Intraluminal renal metastasis from a rectal adenocarcinoma: an unusual site].

Primary adenocarcinoma of the urinary tract are uncommon. But secondary involvement of pyelocalyceal system by metastasis of colorectal origin is rare. We report a case of late rectal metastasis with renal pelvis growth presenting as a pyonephrosis. This study emphasizes the relevance of cytokeratin 7 and 20 immunostaining in such differential diagnosis.

Adenocarcinoma↗

Di-, tri- and tetrameric single chain Fv antibody fragments against human CD19: effect of valency on cell binding.

Single chain variable fragments (scFv) of the murine monoclonal antibody HD37 specific to human B-cell antigen CD19 were constructed by joining the VH and VL domains with linkers of 18, 10, 1 and 0 residues. ScFv-18 formed monomers, dimers and small amounts of tetramers; scFv-10 formed dimers and small amounts of tetramers; scFv-1 formed exclusively tetramers; scFv-0 formed exclusively trimers. The affinities of the scFv-10 (diabody) and scFv-1 (tetrabody) were approximately 1.5- and 2.5-fold higher, respectively, than that of the scFv-0 (triabody). The tetrabody displayed a significantly prolonged association with cell-bound antigen (t1/2 cell surface retention at 37 degrees C of 26.6 min) compared to both the diabody (13.3 min) and triabody (6.7 min). This increase in avidity of the tetrabody combined with its larger size could prove to be particularly advantageous for imaging and the immunotherapy of B-cell malignancies.

Amino Acid Sequence↗

Biochemical characterization and nuclear magnetic resonance structure of novel alpha-conotoxins isolated from the venom of Conus consors.

Two novel alpha-conotoxins were purified and characterized from the venom of the fish-hunting cone snail Conus consors. These peptides were identified by screening HPLC fractions of the crude venom and by binding experiments with Torpedo nicotinic acetylcholine receptor. The toxins named alpha-CnIA and alpha-CnIB exhibited sequences of 14 and 12 amino acids, respectively. The alpha-CnIA represents the main alpha-conotoxin contained in the venom, whereas alpha-CnIB is present in a relatively small amount. Chemical synthesis of alpha-CnIA was carried out using the Fmoc methodology by selective disulfide bond formation. The biological activity of the toxin was assessed in fish and mice. The alpha-CnIA inhibited the fixation of iodinated alpha-bungarotoxin to Torpedo nicotinic acetylcholine receptors with an IC50 of 0.19 microM which can be compared to the IC50 of 0.31 microM found for the previously characterized alpha-MI isolated from the piscivorous Conus magus. The synthetic alpha-CnIA blocked spontaneous and evoked synaptic potentials in frog and mouse isolated neuromuscular preparations at sub-micromolar concentrations. Solution NMR of this toxin indicated a conformational heterogeneity with the existence of different conformers in solution, at slow and intermediate exchange rates relative to the NMR chemical shift time scale, similar to that reported for alpha-GI and alpha-MI. NMR structures were calculated for the major NMR signals representing more than 80% of the population at 5 degrees C.

Amino Acid Sequence↗

Post-traumatic course complicated by cutaneous infection with Absidia corymbifera.

Cutaneous mucormycosis is a rare but serious infection in trauma patients. Reported here is the case of a young patient with cutaneous mucormycosis due to Absidia corymbifera probably caused by a soil-contaminated wound. Despite daily surgical debridement and amphotericin B therapy, cure could be achieved only by amputation of the lower limb.

Absidia↗

The strategy used by some piscivorous cone snails to capture their prey: the effects of their venoms on vertebrates and on isolated neuromuscular preparations.

Three piscivorous Conus species, C. ermineus, C. consor and C. catus were acclimatized in aquaria. The study of their strategy to capture the prey and details of their radula's morphology revealed that all of them used a 'hook and line' strategy which consists of immobilizing the prey rapidly before engulfing it. The venoms from these piscivorous species clearly elicit, when injected into fish, an excitotoxic shock characterized by a sudden tetanus of the prey. In mammals, the venoms induce both flaccid paralysis via i.p. injection and seizures via i.c.v. injection. Intracellular recordings from frog nerve-muscle preparations revealed that the venoms from these Conus species first caused spontaneous synaptic potentials which in turn triggered muscle action potentials. Such spontaneous activity is due to an increased nerve terminal excitability. In addition, the venoms suppressed neuromuscular transmission probably by blocking postsynaptic nicotinic acetylcholine receptors. No direct effect of these Conus venoms was observed on the membrane of skeletal muscle fibres. In conclusion, C. ermineus, C. consor and C. catus, which have not securely tethered their prey used a mixture of toxins which target both pre-and postsynaptic elements of the neuromuscular junction and which produce rapid immobilization of their prey.

Animals↗

Pituitary adenomas with infra-sellar extension into the nasopharynx.

Three cases of pituitary adenomas with infra-sellar extension into the nasopharynx and the nasal cavities are reported. The clinical signs were epistaxis, nasal obstruction, painful sinuses and purulent rhinorrhoea. The initial diagnostic hypothesis was that of a carcinoma of the nasopharynx or the sinuses in all three cases. The diagnosis was made by histological examination and measurement of plasma hormone levels. These cases highlight the difficulty in the diagnosis of such tumours due to their misleading clinical, radiological and histological features.

Adenoma↗

Primary cardiac sarcomas: an immunohistochemical and grading study with long-term follow-up of 24 cases.

AIMS: Primary cardiac sarcomas are rare and aggressive tumours. The aims of this study were to precisely classify cardiac sarcomas according to their pathology, and to determine their clinicopathological features and prognosis. METHODS AND RESULTS: Twenty-four primary cardiac sarcomas were studied. Clinical features and follow-up of all patients were collected. Histological diagnoses were obtained by combining both morphological features as described in soft tissue counterparts and the immunoprofile of the tumours. The 24 cases were classified as undifferentiated sarcoma (nine cases), angiosarcoma (six cases all located in the right atrium), leiomyosarcoma (six cases), malignant fibrous histiocytoma (one pleomorphic and one giant cell type) and synovial sarcoma (one case). Patients included 14 men and 10 women, with a mean age of 46 years. Clinical manifestations were protean, often delaying the diagnosis. Dyspnoea resulting from obstruction of the cardiac chambers was the most common symptom. Echocardiography and magnetic resonance imaging were useful respectively to detect and to evaluate tumour extension. Complete macroscopic resection was possible in only 33% of patients. The most common cause of death was local recurrence of the tumours (50%), even in the cases of complete macroscopic resection. Whatever the treatment, the prognosis was poor with a mean survival of 16.5 months after diagnosis. CONCLUSIONS: All types of sarcomas may be observed in the heart with a predominance of undifferentiated sarcomas. Histological grading, unlike histological type, seems to correlate with survival which remains extremely poor.

Adult↗

A new conotoxin isolated from Conus consors venom acting selectively on axons and motor nerve terminals through a Na+-dependent mechanism.

A novel conotoxin was isolated and characterized from the venom of the fish-hunting marine snail Conus consors. The peptide was identified by screening chromatography fractions of the crude venom that produced a marked contraction and extension of the caudal and dorsal fins in fish, and noticeable spontaneous contractions of isolated frog neuromuscular preparations. The peptide, named CcTX, had 30 amino acids and the following scaffold: X11CCX7CX2CXCX3C. At the frog neuromuscular junction, CcTx at nanomolar concentrations selectively increased nerve terminal excitability so that a single nerve stimulation triggered trains of repetitive or spontaneous synaptic potentials and action potentials. In contrast, CcTx had no noticeable effect on muscle excitability even at concentrations 100 x higher than those that affected motor nerve terminals, as revealed by direct muscle stimulation. In addition, CcTx increased miniature endplate potential (MEPP) frequency in a Ca2+-free medium supplemented with ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N', N'-tetraacetic acid (EGTA). Blockade of voltage-dependent sodium channels with tetrodotoxin (TTX) either prevented or suppressed the increase of MEPP frequency induced by the toxin. CcTx also produced a TTX-sensitive depolarization of the nodal membrane in single myelinated axons giving rise, in some cases, to repetitive and/or spontaneous action potential discharges. In addition, CcTx increased the nodal volume of myelinated axons, as determined using confocal laser scanning microscopy. This increase was reversed by external hyperosmolar solutions and was prevented by pretreatment of axons with TTX. It is suggested that CcTx, by specifically activating neuronal voltage-gated sodium channels at the resting membrane potential, produced Na+ entry into nerve terminals and axons without directly affecting skeletal muscle fibres. CcTx belongs to a novel family of conotoxins that targets neuronal voltage-gated sodium channels.

Action Potentials↗

Quantification of bias related to the extraction of DNA directly from soils.

In recent years, several protocols based on the extraction of nucleic acids directly from the soil matrix after lysis treatment have been developed for the detection of microorganisms in soil. Extraction efficiency has often been evaluated based on the recovery of a specific gene sequence from an organism inoculated into the soil. The aim of the present investigation was to improve the extraction, purification, and quantification of DNA derived from as large a portion of the soil microbial community as possible, with special emphasis placed on obtaining DNA from gram-positive bacteria, which form structures that are difficult to disrupt. Furthermore, we wanted to identify and minimize the biases related to each step in the procedure. Six soils, covering a range of pHs, clay contents, and organic matter contents, were studied. Lysis was carried out by soil grinding, sonication, thermal shocks, and chemical treatments. DNA was extracted from the indigenous microflora as well as from inoculated bacterial cells, spores, and hyphae, and the quality and quantity of the DNA were determined by gel electrophoresis and dot blot hybridization. Lysis efficiency was also estimated by microscopy and viable cell counts. Grinding increased the extracellular DNA yield compared with the yield obtained without any lysis treatment, but none of the subsequent treatments clearly increased the DNA yield. Phage lambda DNA was inoculated into the soils to mimic the fate of extracellular DNA. No more than 6% of this DNA could be recovered from the different soils. The clay content strongly influenced the recovery of DNA. The adsorption of DNA to clay particles decreased when the soil was pretreated with RNA in order to saturate the adsorption sites. We also investigated different purification techniques and optimized the PCR methods in order to develop a protocol based on hybridization of the PCR products and quantification by phosphorimaging.

Actinomycetales↗

[Papillary fibroelastoma of the heart. A review of 20 cases].

After a period during which cardiac papillary fibroelastomas were considered incidental autopsy findings cerebral and coronary arteries embolism proved their aggressiveness. Echocardiography is now able to identify them and surgical resection is rapidly required. Sea anemone like macroscopic pattern is characteristic with finely villous masses, each frond being at microscopical examination formed by a central fibroelastic core surrounded by a myxomatous layer overlied by endothelial cells. Histogenesis remains elusive and we tried to clarify it by immunohistochemical analysis of 8 of the 20 cases studied (10 autopsies, 10 surgical resections). Morphological and immunohistochemical data show that endothelial cells play the most important part in abnormal formations.

Adult↗

[Papillary fibroelastoma: a cardiac tumor rarely reported in children].

Papillary fibroelastoma is a seldom reported tumour. It usually occurs in adults and develops on the aortic and mitral valves. It is not different of giant Lambl excrescences and differential diagnostic can be difficult with the myxoma. Its systematic surgical ablation is justified by the important risk of embolic complications. It has rarely been reported in children. We report a case peculiar by fortuitous diagnostic, tricuspid site, large size and occurrence in a 3-year old child.

Child, Preschool↗

[Conus venoms: a source of toxins which interact with membrane- potential-dependent sodium channels].

Marine snails of the genus Conus, as they are carnivorous predators, have a venom apparatus used to capture their prey. The toxins contained in the venoms of Conidae, called conotoxins, are of a particular high degree of diversity and represent powerful tools in the neuroscience field. Indeed, these toxins specifically bind with a high affinity to receptors and ionic channels. Therefore, they provide original pharmacological tools which receive increasing investigation both to identify and study some functions of the nervous systems and to characterize new types and closely related subtypes of receptors or ionic channels. The voltage-gated sodium channel, because of its fundamental role in cell membrane excitability, is the specific target of a large number of animal and vegetal toxins. Actually, at least seven toxin receptor sites have been identified on this channel-protein. These toxins, and in particular conotoxins, are used to precise the role of different types and/or closely related subtypes of sodium channels in the peripheral and central nervous systems. The focus of the present review is to summarize our current knowledge of the consequences of physiological interactions between different conotoxin families and sodium channels.

Action Potentials↗