Presence of a linear plasmid-like DNA molecule in the fungal pathogen Ceratocystis fimbriata Ell. & Halst.

Summary A plasmid-like molecule was detected in a strain of the ascomycete Ceratocystis fimbriata Ell. & Halst., a pathogenic fungus of Populus spp. The DNA replicon, designated pFQ501, was found to have a linear structure with a length of 6.0 kb (3.9 × 10⁶ daltons) and a density of 1.685 g/cc. This molecule was found to be associated with the mitochondria and was isolated from the gel; its restriction map was deduced from single and double digestions.     

Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice

Mice of the BALB/c strain are widely used in behavioral research in spite of the albino condition, which can obscure brain-behavior relationships. We have developed a pigmented BALB strain, congenic to BALB/c, which could be more appropriate for neurogenetic studies that aim at identifying the effects of neurological mutations on behavior. Comparison of inbred albino and pigmented congenic BALB arising from the same litters provides a valuable tool for detecting the consequences of the albino mutation on behavioral performances. Preliminary results presented here show that the albino condition does not interfere with the development and patterns of connectivity of mossy fibers in the hippocampus. On the other hand, obvious coat color-linked differences appear for locomotor activity and defecation scores in the open field, pigmented mice being unexpectedlyl less active and more reactive than albino, as if better vision increased their reactions to a novel, anxiogenic environment. Finally, pigmented mice do not show better performances in the radial maze, which confirms that the inability of BALB mice for spatial learning in a highly demanding version of this task cannot be attributed to their inability to process visual information.     

Conservative treatment in epithelial ovarian cancer: results of a multicentre study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer) and SFOG (Société Francaise d'Oncologie Gynécologique)

BACKGROUND: Results of conservative management of epithelial ovarian cancer (EOC) remain controversial in the literature. The aim of this study was to assess the clinical outcomes and fertility following fertility-sparing surgical management of EOC in a retrospective multicentre study. METHODS: A multicentre retrospective study was performed by members of two French groups. Six inclusion criteria were defined: (i) Histological review by the same pathologist; (ii) age < or =40 years; (iii) conservative management; (iv) complete peritoneal staging; (v) delivery of a platinum-based chemotherapy in stage > or = IC; and (vi) follow-up >1 year. RESULTS: Thirty-four patients fulfilled the inclusion criteria: 30 had stage IA disease; three had stage IC and one had stage IIA. Eleven patients had recurrence: 10 patients had invasive disease and one had borderline recurrence. Among 10 patients with invasive recurrence, initial stage and grade were: stage IA G1, n = 1; stage IA G2, n = 4; stage IA G3, n = 1; and stage> or = IC, n = 4. All patients with stage > IA had recurrence. Ten pregnancies were observed in nine patients. CONCLUSION: Conservative surgery for patients with EOC could be considered in young patients with stage IA G1 disease. This procedure should not be performed in patients with FIGO stage > IA.     

Evaluation of the professional practices of physicians in transfusion technology and medicine]

The evaluation of the professional practices (EPP) is obligatory for all the physicians since July 1, 2005 for a first five-year period. It represents one of the components of the continuous medical training (CMT). The French Society of Blood Transfusion and National Institute of Blood Transfusion are the promoters of the EPP in transfusion technology and medicine. Initially, the programs of EPP will be conceived and controlled by experts and will relate to their basic activities. During a five years cycle, the physician taking part in a program must validate a specific action and take part in a rolling programme. At the end of the programme, the physician will receive a certificate issued by National Institute of Blood Transfusion and will have to submit it to a committee placed under the responsibility of the regional physicians' committee.     

Prospects for a Vaccine in Allergic Diseases and Asthma

AbstractAllergen-specific immunotherapy is widely used to treat allergic diseases, andcurrent research is now focusing on the development of therapeutic vaccines actingon the IgE immune response following allergen challenge. The IgE immuneresponse is dependent on genetic and environmental factors; production of IgEresults from complex interactions among B cells, T cells, mast cells, basophils,surface and adhesion molecules and various cytokines. New vaccination methods under investigation involve allergen-specific ornonspecific methodology. Allergen-specific methods currently being developedinclude allergoids, passive saturation of effector cells, plasmid DNA immunisationand antigen-antibody complexes. The mechanisms of immunotherapy usingallergen-specific methods differ with the allergens and the route of immunisationused (parenteral, intranasal, sublingual, oral or bronchial). Many vaccines beingdeveloped at present comprise synthetic, recombinant or highly purified subunitantigens, which although they have increased safety may also be less immunogenic.It is hoped that the addition of adjuvants will overcome this drawback. Methods ofincreasing the dose of allergen while reducing the possibility of an anaphylacticreaction include the use of non-anaphylactic isoforms of the allergens, alteration ofthe tertiary structure of the allergens and construction of minimal allergen-derived Tcell peptides. Nonspecific approaches include humanised anti-IgE antibodies,moderation of the T(H)2 cytokine network and antisenseoligodeoxynucleotide therapy.     

Histological detection of minimal metastatic involvement in axillary sentinel nodes: a rational basis for a sensitive methodology usable in daily practice.

There is no consensus method for the histological analysis of axillary sentinel nodes (SN). This study aimed to (1) assess the rate of occult metastases in SN using large serial sectioning and immunohistochemistry (IHC), (2) evaluate whether occult metastases were predictive of metastases in the downstream axillary nodes, and (3) specify a methodology of analysis of SN that could be both sensitive and applicable in daily practice. One hundred three patients with breast carcinoma underwent SN biopsy and then axillary dissection. SN free of tumor at standard examination of one section were sectioned at six levels (150-microm intervals) and immunostained for cytokeratin. The number and localization of labeled metastatic cells (occult metastases) were recorded. In 29 of the 103 patients (28%), SN were found to be metastatic after standard examination. The SN of the remaining 74 patients were further analyzed using IHC. Occult metastases were detected in 35 of these patients (47.3%), leading to an overall SN involvement rate of 62% (29+35/103). In 33 of these 35 cases, the plurality and the dispersion of the immunostained cells implied that the screening of only 3 of the 6 levels would have led to the detection of diagnostic positive events. Only one of the 35 patients (2.8%) with occult metastases showed metastatic lymph node in the downstream axilla. In our series of axillary SN, the analysis of one standard histologic section and, when negative, of only three additional sections after IHC revealed >60% of metastasis or occult metastasis. Metastasis detected by standard analysis had a high predictive value of downstream node metastasis, whereas the predictive value of occult metastasis revealed by IHC was poor. The clinical significance of occult metastases in SN needs to be specified by long-term follow-up analysis.     

The anti-apoptotic factor Bcl-2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF

The TNF family ligand B cell-activating factor (BAFF, BLyS, TALL-1) is an essential factor for B cell development. BAFF binds to three receptors, BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA), but only BAFF-R is required for successful survival and maturation of splenic B cells. To test whether the effect of BAFF is due to the up-regulation of anti-apoptotic factors, TACI-Ig-transgenic mice, in which BAFF function is inhibited, were crossed with transgenic mice expressing FLICE-inhibitory protein (FLIP) or Bcl-2 in the B cell compartment. FLIP expression did not rescue B cells, while enforced Bcl-2 expression restored peripheral B cells and the ability to mount T-dependent antibody responses. However, many B cells retained immaturity markers and failed to express normal amounts of CD21. Marginal zone B cells were not restored and the T-independent IgG3, but not IgM, response was impaired in the TACI-IgxBcl-2 mice. These results suggest that BAFF is required not only to inhibit apoptosis of maturating B cells, but also to promote differentiation events, in particular those leading to the generation of marginal zone B cells.     

Allergy to cooked white potatoes in infants and young children: A cause of severe,chronic allergic disease

BACKGROUND: Cases of allergy to cooked potato in children have been reported, some with immediate and others with late reactions. The clinical effects of chronic allergic reactions to potato and the effectiveness of diet on such reactions have not been described previously. OBJECTIVE: We sought to evaluate the importance of cooked potato as an allergenic food in individual cases of atopy in children. METHODS: Eight atopic children were selected on the basis of suspicion of allergy to cooked potatoes: all had potato-specific IgE, 2 of 8 had experienced immediate allergic reactions, and 6 of 8 had eczema that improved with a potato-elimination diet (decrease in severity scoring of atopic dermatis [SCORAD] index of >50%). The patients were evaluated by using skin prick tests with homemade cooked and noncooked potato extracts and with a commercial extract and by using IgE immunoblots from SDS-PAGE patterns of potato extract. Seven patients were challenged with cooked potato. The control group consisted of 9 age-matched atopic children, 8 of them with eczema. RESULTS: The mean SCORAD index decreased from 43.3 before to 11.5 after elimination of potato from the diet. Potato CAP values ranged from 3.71 to greater than 100 kUa/L. Potato challenge results were positive in 7 of 7 patients. Skin prick test responses were positive for cooked potato extracts in 7 of 7 patients, for noncooked extracts in 7 of 7 patients, and for the commercial extract in 8 of 8 patients compared with in 0 of 9, 1 of 9, and 1 of 9 subjects in the control group, respectively. During immunoblotting, 8 of 8 patient sera recognized one or more protein bands compared with 0 of 9 control subject sera. CONCLUSION: Allergy to cooked potatoes is a cause of severe allergic disease, with immediate reactions and eczema in some atopic infants and young children.     

Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy

The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy.     

Escherichia coli and Staphylococcus aureus elicit differential innate immune responses following intramammary infection

Staphylococcus aureus and Escherichia coli are among the most prevalent species of gram-positive and gram-negative bacteria, respectively, that induce clinical mastitis. The innate immune system comprises the immediate host defense mechanisms to protect against infection and contributes to the initial detection of and proinflammatory response to infectious pathogens. The objective of the present study was to characterize the different innate immune responses to experimental intramammary infection with E. coli and S. aureus during clinical mastitis. The cytokine response and changes in the levels of soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), two proteins that contribute to host recognition of bacterial cell wall products, were studied. Intramammary infection with either E. coli or S. aureus elicited systemic changes, including decreased milk output, a febrile response, and induction of the acute-phase synthesis of LBP. Infection with either bacterium resulted in increased levels of interleukin 1beta (IL-1beta), gamma interferon, IL-12, sCD14, and LBP in milk. High levels of the complement cleavage product C5a and the anti-inflammatory cytokine IL-10 were detected at several time points following E. coli infection, whereas S. aureus infection elicited a slight but detectable increase in these mediators at a single time point. Increases in IL-8 and tumor necrosis factor alpha were observed only in quarters infected with E. coli. Together, these data demonstrate the variability of the host innate immune response to E. coli and S. aureus and suggest that the limited cytokine response to S. aureus may contribute to the well-known ability of the bacterium to establish chronic intramammary infection.