Eric Labouyrie

Expression of neurotrophins and their receptors in human bone marrow.

The expression of neurotrophins and their receptors, the low-affinity nerve growth factor receptor (p75LNGFR) and the Trk receptors (TrkA, TrkB, and TrkC), was investigated in human bone marrow from 16 weeks fetal age to adulthood. Using reverse transcription-polymerase chain reaction, all transcripts encoding for catalytic and truncated human TrkB or TrkC receptors were detected together with trkAI transcripts, whereas trkAII transcripts were found only in control nerve tissues. Transcripts for the homologue of the rat truncated TrkC(ic113) receptor were identified for the first time in human tissue. Stromal adventitial reticular cells were found immunoreactive for all neutrophin receptors. In contrast, hematopoietic cell types were not immunoreactive for p75LNGFR but showed immunoreactivity for one or several Trk receptors. TrkA immunoreactivity was found in immature erythroblasts. Catalytic TrkB immunoreactivity was observed in eosinophilic metamyelocytes and polymorphonuclear cells. Truncated TrkB immunoreactivity was found in erythroblasts and megacaryocytes. Immunoreactivity for both catalytic and truncated TrkC receptor was observed in promyelocytes, myelocytes, some polymorphonuclear cells and megacaryocytes. Neutrophin transcript levels appeared higher at fetal than at adult stages, no variation in Trk family transcript levels was observed. The local expression of neurotrophin genes suggests a wide range of paracrine and/or autocrine mode of action through their corresponding receptors within the bone marrow.

EXPRESSION OF NGF RECEPTORS IN NORMAL AND PATHOLOGICAL HUMAN THYMUS

The expression of NGF receptors was investigated in normal human thymus and in thymic hyperplasias, thymomas and thymic carcinomas. By RT-PCR, we detected TrkAI transcripts encoding for the high-affinity NGF receptor. Western blot analysis showed the presence of both TrkA and p75NGFR proteins. In normal thymuses, epithelial subcapsular and medullar cells were TrkA immunoreactive. Interdigitated medullar cells were stained for both TrkA and p75NGFR. While epithelial cells of normal thymuses or benign thymomas exhibited a TrkA positive-p75NGFR negative phenotype, a switch to a TrkA negative-p75NGFR positive phenotype was observed in malignant epithelial cell tumours and was associated with cell proliferation-associated MIB1 expression. Our results argue for a local role of NGF and its receptors on thymic stromal cells both in normal and neoplastic conditions.

Differential Expression of NGF Receptors in Human Thymic Epithelial Tumors

NGF receptor (TrkA and p75NGFR) expression was investigated in human thymuses, including normal thymuses, thymic hyperplasias, thymomas and thymic carcinomas. TrkAI but not TrkAII transcripts were demonstrated by RT-PCR. In normal thymuses, immunohistochemistry revealed a restricted TrkA-immunoreactivity to epithelial and interdigitated reticular cells, while only interdigitaded reticular cells were immunoreactive for p75NGFR. Thymocytes were negative for both receptors. A switch from the normal TrkA positive-p75NGFR negative phenotype to a TrkA negative-p75NGFR positive phenotype was found in histologically aggressive epithelial cell tumors, suggesting that NGF and its receptors are potentially involved in thymus stroma organogenesis and proliferation.

PRIMARY CARDIAC LYMPHOMA IN AN IMMUNOCOMPETENT WOMAN

We report a fatal primary cardiac non-Hodgkins lymphoma in a 62 years old immunocompetent woman presenting with tamponade and complete atrioventricular block. CT-scan, echocardiography and autopsy examination showed a tumor largely infiltrating the heart without extracardiac involvement. A surgical biopsy revealed high grade B-cell non-Hodgkins lymphoma with a misleading myelomonocytic CD68 (KPI) expression. Polymerase Chain Reaction analysis revealed a clonal rearrangement of the immunoglobulin heavy chain gene and confirmed the B-cell origin of the lymphoma. Our report also emphasizes the role of immunohistochemical and molecular techniques in the diagnosis.

Intérêt et limites de la biopsie endomyocardique au cours de l'infection par le VIH

The authors evaluated the interest of endomyocardial biopsy in 19 consecutively hospitalized patients with AIDS. Histopathological study dit not exhibit opportunistic infection but showed aspecific myocarditis in nine patients.

Benign lymphocytic angiitis and granulomatosis: A T-cell lymphoma?

Benign lymphocytic angiitis and granulomatosis is a T-cell lymphoproliferative disorder confined to the lung and corresponding to a low-grade angiocentric immunoproliferative lesion. Controversy remains as to whether these lesions are lymphomas. We report such a case in an 8-year-old patient with Burkitts lymphoma in remission who presented with persistent bronchopneumopathy and bilateral pulmonary infiltrates on tomodensitometry. Surgical resection revealed the histologic changes of benign lymphocytic angiitis and granulomatosis. Immunohistochemistry showed no aberrant pan T-cell marker loss. Genetic analysis of frozen tissue by Southern blot DNA hybridization with probes to T-cell receptor beta- and gamma-chain genes and to the immunoglobulin heavy chain joining region gene (JH) identified no clonal rearrangement. Search for Epstein-Barr virus-DNA sequences by in situ hybridization and Southern blot analysis provided negative results. Our data imply that lowgrade angiocentric immunoproliferative lesions are not exclusively lymphomas but might represent a borderline lymphoproliferative disease (seen in the course of many diseases), perhaps corresponding to host immune response.