The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4 T cells.

The activation of T cells requires the guanine nucleotide exchange factor VAV1. Using mice in which a tag for affinity purification was attached to endogenous VAV1 molecules, we analyzed by quantitative mass spectrometry the signaling complex that assembles around activated VAV1. Fifty VAV1-binding partners were identified, most of which had not been previously reported to participate in VAV1 signaling.

Themis1 enhances T cell receptor signaling during thymocyte development by promoting Vav1 activity and Grb2 stability.

The T cell signaling protein Themis1 is essential for the positive and negative selection of thymocytes in the thymus. Although the developmental defect that results from the loss of Themis1 suggests that it enhances T cell receptor (TCR) signaling, Themis1 also recruits Src homology 2 domain-containing phosphatase-1 (SHP-1) to the vicinity of TCR signaling complexes, suggesting that it has an inhibitory role in TCR signaling. We used TCR signaling reporter mice and quantitative proteomics to explore the role of Themis1 in developing T cells.

Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.

Lymphomas grow as dense aggregates in patients, but whether this spatial organization affects lymphoma cell biology is unknown. We grew follicular lymphoma (FL) cells in vitro as multicellular aggregates of lymphoma cells to investigate this question. Gene expression analysis revealed that 612 genes were differentially expressed when cells grew in multicellular aggregates of lymphoma cells rather than in suspension.

The gene expression profile of phosphoantigen-specific human γδ T lymphocytes is a blend of αβ T-cell and NK-cell signatures.

Global transcriptional technologies have revolutionised the study of lymphoid cell populations, but human γδ T lymphocytes specific for phosphoantigens remain far less deeply characterised by these methods despite the great therapeutic potential of these cells. Here we analyse the transcriptome of circulating TCRVγ(+) γδ T cells isolated from healthy individuals, and their relation with those from other lymphoid cell subsets. We report that the gene signature of phosphoantigen-specific TCRVγ(+) γδ T cells is a hybrid of those from αβ T and NK cells, with more 'NK-cell' genes than αβ T cells have and more 'T-cell' genes than NK cells.

Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study.

PAX5 is the main target of somatic mutations in acute B lymphoblastic leukemia (B-ALL). We analyzed 153 adult and child B-ALL harboring karyotypic abnormalities at chromosome 9p, to determine the frequency and the nature of PAX5 alterations. We found PAX5 internal rearrangements in 21% of the cases.

PAX5 mutations occur frequently in adult B-cell progenitor acute lymphoblastic leukemia and PAX5 haploinsufficiency is associated with BCR-ABL1 and TCF3-PBX1 fusion genes: a GRAALL study.

Adult and child B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) differ in terms of incidence and prognosis. These disparities are mainly due to the molecular abnormalities associated with these two clinical entities. A genome-wide analysis using oligo SNP arrays recently demonstrated that PAX5 (paired-box domain 5) is the main target of somatic mutations in childhood BCP-ALL being altered in 38.

Decreased motivational properties of morphine in mouse models of cancerous- or inflammatory-chronic pain: implication of supraspinal neuropeptide FF(2) receptors.

Our main purpose was to evaluate the influence of cancer pain on the rewarding properties of morphine. Opioids are very addictive when used by healthy persons, conversely the occurrence of an opioid addiction seems very low when patients suffering from cancer are treated with morphine. We investigated the reinforcing properties of morphine in the place preference paradigm on a new model of mice suffering from a cancer pain induced by syngenic melanoma cells injected in the hind paw.

[An exceptional cause of renal colic. Castleman's tumor. Lymphonodular angiofollicular hyperplasia].

The case of a 38-year-old man with renal colic due to compression by an abdominopelvic mass is reported. Histologic examination of the mass led to the diagnosis of giant lymph node hyperplasia or Castleman disease. Surgical removal of the lesion ensured complete recovery with no recurrence after 32 months follow up.

In situ immunologic characterization of follicular lymphomas.

Surface markers were studied in a series of follicular lymphomas with immunofluorescence on frozen sections (39 cases) and on cell suspensions (21 cases), and with immunoperoxidase on frozen sections using a panel of 15 monoclonal antibodies (17 cases). With immunofluorescence on frozen sections, 22/39 cases showed monotypic sIg (IgMK: 14 cases, IgML: 7 cases, M: 1 case). In the remaining 17 cases the neoplastic follicles were negative.

[Chronic diarrhea in nonspecific colopathies in children. Trial of etiological classification].

305 children with non specific colopathies were studied with respect to the etiologic factors which may be responsible for the onset of the diarrheic syndrome. Epidemiologic factors (ethnic group, mode of housing, standard of living, parents's age and profession) did not appear to play a significant role and studies of familial and personal histories did not appear to be of any help. On the contrary, analysis of the diet showed a high incidence of nutritional imbalances (75.

Richter's syndrome. Evidence for the clonal origin of the two proliferations.

A case of Richter's syndrome was investigated by several technics: light and electron microscopy, surface markers, immunohistological studies and immunoelectron microscopy. On light microscopy lymph node proliferation was composed of large lymphoid cells, some exhibiting Reed-Sternberg like features. On electron microscopy many intermediary cells, from small lymphocytes to immunoblasts and plasma cells, were noted.

Granulomatous hepatitis in Q fever.

Liver lesions in 17 patients with serologically diagnosed Q fever are described. A distinctive granulomatous pattern, with granuloma formation plus a fibrinoid ring, was observed in 14 cases. In two cases the fibrinoid material consisted of fibrillar eosinophilic structures without an annular arrangement, interspersed among epithelioid cells.

[Pulmonary allescheriosis (author's transl)].

In a patient properly treated for a previous cavitary tuberculosis, we had the surprise, after hemoptyses, to find a sleigh-bell shaped picture suggesting an intra-cavitary aspergilloma with a very special mycosis with Allescheria Boydii. Proof was provided by the presence of the fungus in direct examination and in culture in bronchial secretions. Surgical exeresis did not cure the patient and a secondary recurrence appeared on which antifungal drugs were ineffective.

[Recurrent bronchopneumopathies caused by gastroesophageal reflux in children. Clinical, x-ray and histologic studies of 36 cases].

The respiratory symptoms of gastro-oesophageal reflux, which sometimes includes massive and fatal inhalation, are well-known in infants. In older children the digestive signs are not clinically evident and the reflux mainly, if not exclusively, can be translated by recurring respiratory symptoms. The series of 36 cases presented in this work concerns children between 3 months and 15 years old, for whom the first signs were respiratory, with often a silent gastro-oesophageal reflux for several months, and even several years in some cases.

[Dysimmunologic and pseudolymphomatous adenopathies. II. Lymphadenopathies rich in epithelial cells].

Besides the dysimmunitary and pseudo-lymphomatous adenopathies rich in immunoblasts and plasmocytes (ADPL type I) five cases showed similar clinical and biological data but with frequently otorhinolaryngologic location. The lesions are characterized by important structural changes and abundant epithelioid cells are comparable to Lukes' type III immunoblastic lymphadenopathies and to Lennert's lymphoepithelioid lymphomas. They must be distinguished from Hodgkin's granulomas which are rich in epithelioid cells.

[Dysimmunologic and pseudolymphomatous adenopathies. I. Immunoblastic and plasmocytic lymphadenopathies].

The authors report 9 cases with pseudo-lymphomatous lesions associated with dysimmunitary features. They discuss the correlations between these cases and similar entities, for instance angio-immunoblastic lymphadenopathy (LAID). It seems that all these anatomoclinical syndromes could be referred to as dysimmunitary and pseudolymphomatous adenopathies (ADPL).