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Biomedical subjects

L de Leval

Publications and source records attributed to L de Leval.

At least 19 recordsLinked to original sources

Cloning of the genome of Alcelaphine herpesvirus 1 as an infectious and pathogenic bacterial artificial chromosome.

Alcelaphine herpesvirus 1 (AlHV-1), carried asymptomatically by wildebeest, causes malignant catarrhal fever (MCF) following cross-species transmission to a variety of susceptible species of the order Artiodactyla. The study of MCF pathogenesis has been impeded by an inability to produce recombinant virus, mainly due to the fact that AlHV-1 becomes attenuated during passage in culture. In this study, these difficulties were overcome by cloning the entire AlHV-1 genome as a stable, infectious and pathogenic bacterial artificial chromosome (BAC). A modified loxP-flanked BAC cassette was inserted in one of the two large non-coding regions of the AlHV-1 genome. This insertion allowed the production of an AlHV-1 BAC clone stably maintained in bacteria and able to regenerate virions when transfected into permissive cells. The loxP-flanked BAC cassette was excised from the genome of reconstituted virions by growing them in permissive cells stably expressing Cre recombinase. Importantly, BAC-derived AlHV-1 virions replicated comparably to the virulent (low-passage) AlHV-1 parental strain and induced MCF in rabbits that was indistinguishable from that of the virulent parental strain. The availability of the AlHV-1 BAC is an important advance for the study of MCF that will allow the identification of viral genes involved in MCF pathogenesis, as well as the production of attenuated recombinant candidate vaccines.

Animals↗

[Laparoscopic liver resection of a hydatid cyst].

Most of the echinococcosis cases treated in Belgium are contracted in African and Mediterranean countries. In this paper the authors describe the case of a Mediterranean patient suffering from a hepatic hydatid cyst treated by oral albendazole and laparoscopic liver resection.

Adult↗

A new model for human intestinal preservation: comparison of University of Wisconsin and Celsior preservation solutions.

AIM: We compared University of Wisconsin (UW) and Celsior preservation solutions using a new model of human intestinal preservation that mimics the clinical conditions of small bowel procurement. METHODS: Intestinal grafts were harvested from four multiorgan donors. After classic warm dissection for organ procurement, an ileal segment of 50 cm was immediately flushed with Celsior. After the perfusion of the abdominal organs with UW, a second segment of adjacent ileum was harvested. The two intestinal grafts were then divided into segments by stapling, before immersion into the corresponding preservation solution (Celsior or UW) for 0-, 6-, 12-, or 24-hour incubation at 4 degrees C. A histological score was graded after blinded examination of three random specimens within each ileal graft for each duration of preservation. RESULTS: Control specimens showed normal histology. After 6 hours of preservation, most villi showed complete epithelial detachment although the crypts appeared intact. After 12 hours of preservation, a larger proportion of the villi showed extensive epithelial sloughing. After 24 hours, the damage involved the entire mucosa with the crypt epithelium largely detached from the basal membrane. No statistical difference in histological score was observed between the two preservation solutions. CONCLUSION: This study showed severe histological alterations of graft mucosa after short periods of preservation by UW or Celsior solutions. This model may be useful to evaluate improvements in the quality of preservation of human intestinal transplants.

Adenosine↗

NF- kappa B2/p100 induces Bcl-2 expression.

The NF-kappaB2/p100 and bcl-3 genes are involved in chromosomal translocations described in chronic lymphocytic leukemias (CLL) and non-Hodgkin's lymphomas, and nuclear factor kappaB (NF-kappaB) protects cancer cells against apoptosis. Therefore, we investigated whether this transcription factor could modulate the expression of the Bcl-2 antiapoptotic protein. Bcl-2 promoter analysis showed multiple putative NF-kappaB binding sites. Transfection assays of bcl-2 promoter constructs in HCT116 cells showed that NF-kappaB can indeed transactivate bcl-2. We identified a kappaB site located at position -180 that can only be bound and transactivated by p50 or p52 homodimers. As p50 and p52 homodimers are devoid of any transactivating domains, we showed that they can transactivate the bcl-2 promoter through association with Bcl-3. We also observed that stable overexpression of p100 and its processed product p52 can induce endogenous Bcl-2 expression in MCF7AZ breast cancer cells. Finally, we demonstrated that, in breast cancer and leukemic cells (CLL), high NF-kappaB2/p100 expression was associated with high Bcl-2 expression. Our data suggest that Bcl-2 could be an in vivo target gene for NF-kappaB2/p100.

B-Cell Lymphoma 3 Protein↗

Variability in immunophenotype in diffuse large B-cell lymphoma and its clinical relevance.

Diffuse large B-cell lymphoma (DLBCL), the single largest category of lymphoma, is a clinically and biologically heterogeneous disease entity. Clinically, patients differ in their mode of presentation and respond variably to therapy. A combination of clinical parameters can be used to predict the patient's response to therapy and survival. The pathological variability of DLBCL is expressed in morphology, immunophenotype, cytogenetic and molecular genetic features. Numerous markers detectable by immunohistochemistry and linked to different aspects of tumour biology have been studied in DLBCL, including lineage-associated and immune markers, proliferation and apoptosis markers, cell adhesion molecules, and more recently stage-specific markers of B-cell differentiation. This review summarizes these studies in regard to their clinical significance and in the light of recent advances in our understanding of the molecular pathology and histogenesis of DLBCL.

Apoptosis↗

[Anatomic-clinical confrontation. Large pelvic mass in a young man].

The authors report the case of a gastro-intestinal stromal tumor (GIST) with unusual clinico-pathological features, presenting as a large cystic rectal mass in a young man. The differential diagnosis of pelvic masses is discussed. In light of this case, the recent literature related to the pathogenesis, diagnosis and treatment of GIST is reviewed.

Adult↗

[Chronic thoracic pain].

The etiological diagnosis of chronic thoracic pain is wide, from benign mechanical disorders to tumors. Reaching the exact diagnosis in often time consuming. Despite the availability of new techniques of imagery, a meticulous clinical history and physical examination remain mandatory. They will lead the exploration. Idiopathic intercostal neuralgia does not exist.

Aged↗

MCP-1 modulates chemotaxis by follicular lymphoma cells.

The localization and establishment of follicular lymphoma (FL) cells in distinct anatomic sites probably involves chemokine and adhesion receptors on the neoplastic cells and appropriate chemokines and adhesion receptor ligands in the microenvironment. Several chemokines play an important role in normal B-cell trafficking and differentiation. Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine that induces chemotaxis of a variety of lymphoid cells through its receptor CCR2. CCR2 is also expressed on B cells, and MCP-1 induces chemotaxis of normal B cells. In this report, we investigated expression and function of CCR2 on FL cells. We found FL cells as well as the t(14; 18)+ B-cell lymphoma line H2 expressed CCR2. MCP-1 potentiated SDF-1-induced chemotaxis of FL cells and H2 cells, but MCP-1 alone did not induce chemotaxis. The specificity of the effects of MCP-1 and SDF-1 was demonstrated by antibody blocking studies. Because FL cells are generally associated with follicular dendritic cells (FDCs), FDCs may be an important source of chemokines. We found that cultured FDCs produced MCP-1, and this production was enhanced by tumour necrosis factor. These data implicate MCP-1 in the migration and localization of FL cells.

Antibodies, Monoclonal↗

Peripheral T-cell lymphoma with follicular involvement and a CD4+/bcl-6+ phenotype.

A truly follicular pattern is thought to be restricted to B-cell lymphomas. We observed a prominent follicular growth pattern in three cases of nodal peripheral T-cell lymphomas, of which two were initially diagnosed as follicular lymphomas. All three patients were male, ranged in age from 50 to 70 years, and had generalized lymphadenopathy at the time of diagnosis. The follicles were sharply demarcated in two cases and large and vague in one case; in all cases, they contained abundant follicular dendritic cells. Neoplastic cells were small to medium, with irregular cleaved or round nuclei and clear cytoplasm, which was abundant in one case. Lymphoma cells in all cases were CD4+ CD8- CD57- bcl-6, with CD10 coexpression in 2 cases. Clonal rearrangement of the gamma chain of the T-cell receptor gene was demonstrated in each case. These cases expand the differential diagnosis of lymphomas with a follicular growth pattern and suggest that neoplastic T cells may have the capacity to induce or home to follicular structures.

Antigens, Neoplasm↗

Cutaneous b-cell lymphomas of follicular and marginal zone types: use of Bcl-6, CD10, Bcl-2, and CD21 in differential diagnosis and classification.

Cutaneous follicular lymphomas (FLs) and cutaneous B-cell lymphomas of extranodal marginal zone (MZL)/mucosal-associated lymphoid tissue (MALT) type may have morphologic overlap, despite the fact that they are thought to be of distinct derivation (germinal center vs. postgerminal center). The problem is compounded by the reported absence of bcl-2 expression by many cutaneous FLs, leading to speculation that cutaneous FL may be unrelated to nodal FL. The authors analyzed the expression of the germinal center-associated antigens bcl-6 and CD10 and of bcl-2 in 18 cutaneous B-cell lymphomas (10 FLs and eight MZLs), in relationship to CD21+ follicular structures, to clarify the relationship of nodal to cutaneous FLs and to explore the value of these antigens in differential diagnosis. The authors studied 10 cutaneous FLs (seven primary and three secondary) and eight MZLs (six primary and two secondary). The FLs (found in six men and four women age 45-75 years) involved the trunk (n = 3) and scalp, face and neck (n = 7). The MZLs (found in five women and three men age 34-81 years) involved the trunk (n = 4), face and neck (n = 2), and arm (n = 2). Immunostaining for CD21, bcl-6, CD10, and bcl-2 allowed the delineation of compartments within the tumors and yielded distinct patterns of staining in FL and MZL. In both follicular and interfollicular/diffuse areas of FL the neoplastic cells were bcl-6+ (10 of 10), often CD10+ (seven of 10, four of seven primary), and bcl-2+ (nine of 10, six of seven primary). Only three of seven cases (one of five primary) had bcl-2 rearrangement detectable by polymerase chain reaction. In the MZLs, the neoplastic B-cells were bcl-6-, CD10-, and bcl-2+ (eight of eight). Three patterns of CD21+ follicles were identified in MZL: reactive germinal centers, uniformly bcl-6+, CD10+, and bcl-2- (five of eight MZLs); colonized follicles, both bcl-6-, bcl-2+, and L26+ cells, and bcl-6+ and bcl-2- cells (five of eight MZLs); and expanded/colonized follicular dendritic cell meshworks, bcl-6- and bcl-2+ B cells with rare residual bcl-6+ and bcl-2- cells (four of eight MZLs). The authors conclude that cutaneous FLs express bcl-6 uniformly, usually express CD10 and bcl-2, and have a follicular pattern similar to nodal FL and consistent with a germinal center origin. The immunophenotype of cutaneous FL is distinct from that of cutaneous MZL, which is negative for bcl-6 and CD10. Colonized follicles in MZL, identified by CD21+ follicular dendritic cell meshworks, contained numerous bcl-6- and bcl-2+ B cells, and were readily distinguished from neoplastic follicles in FL. Conversely, CD21- interfollicular and diffuse areas in FLs contained bcl-6+ and CD10+ cells, which were not seen in diffuse areas of MZLs. Thus, the combination of bcl-2, bcl-6, and CD21 staining is useful for the distinction of cutaneous MZL from cutaneous FL.

Adult↗

Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells?

Primary mediastinal large B-cell lymphomas (LBCLs) constitute a unique subtype of diffuse LBCLs, with distinct clinical, immunophenotypic, and morphologic features. These lymphomas are thought to originate from the thymus, and it has been hypothesized that they derive from a population of B lymphocytes normally present in the thymic medulla. Most diffuse LBCLs harbor somatic mutations in their immunoglobulin genes, suggesting that they have been exposed to the germinal center. To investigate the possible relationship of mediastinal LBCLs to germinal center B cells, we analyzed the expression of bcl-6 and CD10 in 19 mediastinal LBCLs, using an immunoperoxidase technique on formalin-fixed tissue. We found that 19 of 19 (100%) mediastinal LBCLs were bcl-6+ and 6 of 19 (32%) mediastinal LBCLs were CD10+. Because mediastinal LBCLs usually lack BCL-6 gene rearrangement or mutations, expression of bcl-6 and CD10 in these tumors tends to support a germinal center derivation.

Adolescent↗

Detection of the 67-kD laminin receptor in prostate cancer biopsies as a predictor of recurrence after radical prostatectomy.

OBJECTIVES: Reliable prognostic indicators are needed for a better pretherapeutic assessment of the agressiveness of organ-confined prostate cancer (PC) lesions. The 67-kD laminin receptor (67LR) is a cell-surface-associated protein involved in the acquisition of the invasive and metastatic phenotype of a variety of human cancer cell types. We have previously shown that 67LR detection in PC tissues from radical prostatectomy (RP) specimens is an independent predictor of biochemical (PSA) relapse in patients with clinically localized PC. In this study, we assessed 67LR detection in diagnostic PC biopsies as a predictor of biochemical relapse after RP. METHODS: Diagnostic biopsy and subsequent RP tissue specimens from 151 patients with clinically localized PC were immunohistochemically analyzed for 67LR expression. The level of 67LR expression was evaluated by both intensity and extent of the staining. Clinicopathological preoperative and postoperative parameters, including 67LR expression, were correlated with each other and tested as predictors of biochemical relapse. RESULTS: 67LR was detected in 67.5 and 68.2% of biopsies and RPs, respectively. 67LR detection in RP specimens was an independent predictor of relapse. The level of 67LR expression in the biopsy was significantly associated with the biopsy Gleason score (p<0.05) but failed to predict the pathological stage (p>0.1). Biochemical progression-free estimates for patients whose biopsy did or did not express the protein differed with only borderline statistical significance (p = 0.05). Multivariate analysis identified biopsy Gleason score as the only independent preoperative predictor of recurrence. Significant discrepancies in levels of 67LR expression were found between matched biopsy and RP specimens (p<0.05), with exact agreement rates <40%. CONCLUSIONS: 67LR detection in PC biopsies was not a significant preoperative predictor of outcome after RP. Heterogeneity of 67LR expression and biopsy sampling errors most likely represented the main reasons for discordant results between biopsy and RP specimens.

Adenocarcinoma↗