The antimicrobial antiproteinase elafin binds to lipopolysaccharide and modulates macrophage responses

Lipopolysaccharides (LPS) of the outer membrane of Gram-negative bacteria represent a primary target for innate immune responses. We demonstrate here that the antimicrobial/anti-neutrophil elastase full-length elafin (FL-EL) is able to bind both smooth and rough forms of LPS. The N-terminus was shown to bind both forms of LPS more avidly. We demonstrate that the lipid A core-binding proteins polymyxin B (PB) and LPS-binding protein (LBP) compete with elafin for binding, and that LBP is able to displace prebound elafin from LPS. When PB, FL-EL, N-EL, and C-EL were pre-incubated with LPS before addition to immobilized LBP, PB was the most potent inhibitor of LPS transfer to LBP. These data prompted us to examine the biological consequences of elafin binding to LPS, using tumor necrosis factor (TNF)-alpha release by murine macrophages. In serum-containing conditions, N-EL had no effect, whereas both C-EL and FL-EL inhibited TNF-alpha production. In serum-free conditions, however, all moieties had a stimulatory activity on TNF-alpha release, with C-EL being the most potent at the highest concentration. The differential biological activity of elafin in different conditions suggests a role for this molecule in either LPS detoxification or activation of innate immune responses, depending on the external cellular environment.     

Use of the omp50 gene for identification of Campylobacter species by PCR

We studied the prevalence of the omp50 gene and the Omp50 protein in Campylobacter strains. Immunodetection assays and DNA-DNA hybridizations showed that most C. coli strains tested were negative and most C. jejuni and C. lari strains tested were positive. A PCR assay was developed, using the omp50 gene as a species-specific target. We propose a combination of a hippurate test and an omp50 assay to perform identification of Campylobacter species.     

Inflammatory malignant fibrous histiocytomas and dedifferentiated liposarcomas: histological review, genomic profile, and MDM2 and CDK4 status favour a single entity

Inflammatory malignant fibrous histiocytoma (inflammatory MFH) is a very rare tumour that occurs most often in the retroperitoneum. So far, it has been considered to be a special subtype of MFH. As it is now widely accepted that most retroperitoneal pleomorphic MFHs are dedifferentiated liposarcomas, the present study compared histological features, genomic profile (CGH analysis), and MDM2 and CDK4 status (immunohistochemistry, FISH, and quantitative PCR) in inflammatory MFHs from 12 patients and dedifferentiated liposarcomas that had an inflammatory MFH component from eight patients. Metaphase cytogenetic and FISH analyses were also performed on one inflammatory MFH. Histological review showed areas of well-differentiated liposarcoma in nine inflammatory MFHs. CGH analysis showed 12q13-15 amplification or gain in six of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Immunohistochemistry showed positivity of tumour cells for MDM2 in every tumour in both groups and for CDK4 in ten and seven inflammatory MFHs and dedifferentiated liposarcomas, respectively. Metaphase cytogenetic and FISH analysis performed on one inflammatory MFH showed the presence of a supernumerary large marker chromosome and ring chromosome with high-level amplification of both MDM2 and CDK4 genes. FISH analysis on paraffin wax-embedded sections showed amplifications of MDM2 and CDK4 in seven of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Quantitative PCR showed amplification of MDM2 in six and of CDK4 in seven of nine inflammatory MFHs. In conclusion, this study strongly suggests that most so-called inflammatory MFHs are dedifferentiated liposarcomas.     

The arterial supply of the coracoid process

Objective

The aim of this study was to describe the arterial supply of the coracoid process and to define its possible involvement in complications of Latarjet procedure.

Method

Five shoulder dissections were performed to highlight the extraosseous blood supply of the coracoid process. Postmortem arteriographies of the upper limb were performed. Diaphanization of a scapula enabled to view its intraosseous blood supply.

Results

The vertical part of coracoid process was supplied by supra-scapular artery, and the horizontal part by branches of the axillary artery.

Discussion and conclusion

This anatomical study has shown that the coracoid process had its own blood supply. During the Latarjet procedure, vascular sacrifices are mandatory to allow coracoid process transfer to the scapular neck. Such sacrifices could explain lysis or non-union of the coracoid process after Latarjet procedure. Preservation of axillary artery branches supplying horizontal part of the coracoid process could be a possible solution to prevent non-union and lysis of the bone transfer.     

Does the HBZ gene represent a new potential target for the treatment of adult T-cell leukemia?

Links between human T-cell leukemia virus type 1 and adult T-cell leukemia (ATL) were first suspected in 1980. Provirus integration has since been found in all ATL cells. Although the viral Tax protein is involved in the proliferation of the infected cells during the preleukemic stage, Tax expression is not systematically detected in primary leukemic cells. Recent studies found that the viral HBZ gene was always expressed in leukemic cells, suggesting its involvement in the progression of the infected cells toward malignancy. How could this new discovery be translated into possible new avenues for the prevention or treatment of ATL?     

Cyto-histological correlations in primary, recurrent, and metastatic bone and soft tissue osteosarcoma. Institut Curie's experience

To determine diagnostic cytomorphologic features of osteosarcoma on fine-needle aspiration materials, we reviewed the cytologic material and corresponding histologic slides of 126 tumors in 107 patients. Fifty-five (43.6%) tumors were primary, 31 (24.6%) were recurrent, and 40 (31.8%) were metastatic. Review of original cytology reports revealed that 120 (95.3%) tumors were diagnosed as malignant. Six (4.7%) cases were reported as suspicious, false-negative, or unsatisfactory samples.Our findings showed that osteoblastic roundish cells, spindle-shaped cells, reactive giant cells, and osteoid were the most consistent features representative of osteosarcoma. Periosteal reactions, fractures with callous formation, giant cells of osteoclastic type in various conditions, chondrosarcoma with enchondral ossification are entities to consider in the differential diagnosis.     

Intranasal coadministration of live lactococci producing interleukin-12 and a major cow's milk allergen inhibits allergic reaction in mice

The Th1/Th2 balance deregulation toward a Th2 immune response plays a central role in allergy. We previously demonstrated that administration of recombinant Lactococcus lactis strains expressing bovine beta-lactoglobulin (BLG), a major cow's milk allergen, partially prevents mice from sensitization. In the present study, we aimed to improve this preventive effect by coadministration of L. lactis BLG and a second recombinant L. lactis strain producing biologically active interleukin-12 (IL-12). This L. lactis strain producing IL-12 was previously used to enhance the Th1 immune response in a tumoral murine model (L. G. Bermúdez-Humarán et al., J. Immunol. 175:7297-7302, 2005). A comparison of the administration of either BLG alone or BLG in the presence of IL-12 was conducted. A BLG-specific primary Th1 immune response was observed only after intranasal coadministration of both L. lactis BLG and IL-12-producing L. lactis, as demonstrated by the induction of serum-specific immunoglobulin G2a (IgG2a) concomitant with gamma interferon secretion by splenocytes, confirming the adjuvanticity of IL-12-producing L. lactis. Immunized mice were further sensitized by intraperitoneal administration of purified BLG, and the allergic reaction was elicited by intranasal challenge with purified BLG. Mice pretreated with BLG in either the presence or the absence of IL-12 were rendered completely tolerant to further allergic sensitization and elicitation. Pretreatment with either L. lactis BLG or L. lactis BLG and IL-12-producing L. lactis induces specific anti-BLG IgG2a production in serum and bronchoalveolar lavage (BAL) fluid. Although specific serum IgE was not affected by these pretreatments, the levels of eosinophilia and IL-5 secretion in BAL fluid were significantly reduced after BLG challenge in the groups pretreated with L. lactis BLG and L. lactis BLG-IL-12-producing L. lactis, demonstrating a decreased allergic reaction. Our data demonstrate for the first time (i) the induction of a protective Th1 response by the association of L. lactis BLG and IL-12-producing L. lactis which inhibits the elicitation of the allergic reaction to BLG in mice and (ii) the efficiency of intranasal administration of BLG for the induction of tolerance.