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Biomedical subjects

Christine Lefebvre

Publications and source records attributed to Christine Lefebvre.

5 recordsLinked to original sources
PubMed2006

Composite splenic marginal zone lymphoma and mantle cell lymphoma arising from 2 independent B-cell clones.

We report the first case of composite lymphoma involving both mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL) with circulating villous lymphocytes. Morphological, immunohistochemical, immunophenotyping, as well as detailed genetic studies (fluorescence in situ hybridization, IGVH gene sequencing), were performed and confirmed the existence of 2 independent, unrelated tumor clones. The MCL component expressed IgMD lambda, was CD5+, harbored a t(11;14)(q13;q32) involving CCND1, and showed an unmutated VH1-18 gene rearrangement. The SMZL component expressed IgMD kappa, was CD5-, showed a t(10;14)(q24;q32) and an unmutated VH3-7 gene rearrangement. Interestingly, this t(10;14) targeted the NFKB2 gene. Only a single other case of SMZL with t(10;14)/NFKB2 has been reported. Taken together, these data indicate that the MCL and SMZL arose as a consequence of independent malignant transformation events within an antigen-naive B-cell population. This case highlights the importance of a multidisciplinary approach and tissue diagnosis in these complex situations.

Aged↗
PubMed2005

Differences in nuclear positioning of 1q12 pericentric heterochromatin in normal and tumor B lymphocytes with 1q rearrangements.

The frequent rearrangement of chromosome band 1q12 constitutive heterochromatin in hematologic malignancies suggests that this rearrangement plays an important pathogenetic role in these diseases. The oncogenic mechanisms linked to 1q12 heterochromatin are unknown. Constitutive heterochromatin can epigenetically regulate gene function through the formation of transcriptional-silencing compartments. Thus, as a first step toward understanding whether 1q12 rearrangements might compromise such activity in tumor cells, we investigated the 3-D organization of the 1q12 heterochromatin domain (1q12HcD) in normal and tumor B lymphocytes. Strikingly, in normal B cells, we showed that the 1q12HcD dynamically organizes to the nuclear periphery in response to B-cell receptor engagement. Specifically, we observed an almost twofold increase in 1q12Hc domains at the extreme nuclear periphery in activated versus resting B lymphocytes. Remarkably, 1q12Hc organization was noticeably altered in tumor cells that showed structural alterations of 1q12; the 1q12Hc domains were significantly displaced from the extreme nuclear periphery compared to normal activated B lymphocytes (P > 0.0001), although overall peripheral localization was maintained. In a case in which there was a translocation of IGL enhancer to 1q, the altered nuclear positioning of the 1q12HcD was even more pronounced (5% of the 1q12Hc domains at the nuclear periphery compared to 20% in other lymphoma lines), and we were able to mimic this effect in two additional B-cell tumor lines by treatment with trichostatin A, a histone deacetylase (HDAC) inhibitor. Taken together, these results point to the 1q12HcD having a specific, nonrandom, and regulated peripheral organization in B lymphocytes. This organization is significantly disrupted in lymphoma cells harboring 1q rearrangements.

B-Lymphocytes↗
PubMed2003

Testing curvatures of learning functions on individual trial and block average data.

Many models offer different explanations of learning processes, some of them predicting equal learning rates between conditions. The simplest method by which to assess this equality is to evaluate the curvature parameter for each condition, followed by a statistical test. However, this approach is highly dependent on the fitting procedure, which may come with built-in biases difficult to identify. Averaging the data per block of training would help reduce the noise present in the trial data, but averaging introduces a severe distortion on the curve, which can no longer be fitted by the original function. In this article, we first demonstrate what is the distortion resulting from block averaging. The block average learning function, once known, can be used to extract parameters when the performance is averaged over blocks or sessions. The use of averages eliminates an important part of the noise present in the data and allows good recovery of the learning curve parameters. Equality of curvatures can be tested with a test of linear hypothesis. This method can be performed on trial data or block average data, but it is more powerful with block average data.

Artifacts↗
PubMedDate not supplied

Visual object agnosia as a problem in integrating parts and part relations.

Current models of vision generally assume that the recognition of visual objects is achieved by encoding their component parts, as well as the spatial relations among parts. The current study examined how the processing of parts and their configurations may be affected in visual agnosia due to brain damage. Both a visual agnosic patient (AR) and healthy control subjects performed a visual search task in which they had to discriminate between targets and distractors that varied according to whether they shared their parts and/or their configuration. The results show that AR's visual search rates are disproportionally slow when targets and distractors share the same configuration than when they have different configurations. AR is also found to be disproportionately slow in discriminating targets and distractors that share identical parts when the targets and distractors share the same configuration. With differently configured targets and distractors, AR shows no part sharing effect. For controls, in contrast, the part and configuration sharing effects occur independently of one another. It is concluded that AR's object recognition deficit arises from difficulties in discriminating objects that share their configuration, and from an abnormal dependency of part information processing upon object configuration.

Adult↗