Recurring bone epithelioid hemangioma

Bone vascular tumors are very rare. Epithelioid types are described according to their architecture, their degree of vascular differentiation, and their cytonuclear atypia. The include epithelioid hemangioma, epithelioid hemangioendothelioma, and angiosarcoma. We report a case of L4 corpus vertebral bone epithelioid hemangioma. The patient was a 25-year-old man with a tumor that recurred twice. The lesion was characterized by a vascular lumen lined by cells with regular nuclei and inflammatory infiltrates. Capillaries were lined by prominent epithelioid endothelial cells, associated with CD31+ and cytokeratin-.     

Transduction of dendritic cells by antigen-encoding lentiviral vectors permits antigen processing and MHC class I-dependent presentation

BACKGROUND: Because antigen-presenting dendritic cells (DCs) play a major role in the polarization of T cells, including T(H)2 cells involved in allergy, strategies to modify DCs genetically are required. OBJECTIVE: The purpose of this investigation was to transduce murine bone marrow-derived DCs with lentiviral vectors encoding antigen to demonstrate antigen processing and MHC class I-dependent presentation. METHODS: Bone marrow leukocytes were incubated with antigen-encoding lentiviral constructs and cultured with GM-CSF, IL-4, and Flt-3 ligand. The capacity of the resulting DCs to express, process, and present antigen was tested in vitro. RESULTS: An average of 40% of DCs expressed antigen after 1 week of culture when antigen encoded by the lentiviral vector construct was green fluorescent protein. To demonstrate that transduced antigen can be presented by DCs on MHC class I, we chose the lymphocytic choriomeningitis virus glycoprotein (gp) as a model antigen, inasmuch as it is recognized by CD8 T cells from transgenic mice expressing an MHC class I-restricted T-cell receptor specific for the epitope of positions 33 through 41 of gp. DCs transduced with lentiviral construct encoding gp and matured with LPS activated transgenic T cells in an antigen-specific fashion. Using transporter associated with antigen presentation (TAP)-deficient mice, we show that presentation of the gp33-41 epitope is TAP-dependent, confirming processing of gp by the endogenous pathway. CONCLUSIONS: These results demonstrate that CD8 T cells can recognize MHC class I epitopes processed from antigen in DCs transduced with lentiviral vectors. Lentiviral transduction of DCs and antigen presentation to CD8 T cells could be exploited for immunotherapy, because allergen-specific CD8 T cells have been shown to be suppressive in IgE-dependent allergy models.     

Early steps of a thymic tumor in SV40 transgenic mice: hyperplasia of medullary epithelial cells and increased mature thymocyte numbers disturb thymic export

Bone marrow progenitors migrate to the thymus, where they proliferate and differentiate into immunologically competent T cells. In this report we show that mice transgenic for SV40 T and t antigens under the control of the L-pyruvate kinase promoter develop, in a first step, thymic hyperplasia of both thymocytes and epithelial cells. Morphological studies (histology, immunohistolabeling and electron microscopy) revealed modifications of the thymic microenvironment and gradual expansion of medullary epithelial cells in 1 month-old mice, taking over the cortical region. Then, a thymic carcinoma develops. Two-color labeling of frozen sections identified the transgene in medullary epithelial cells. Flow cytometry analysis demonstrated a marked increase in mature CD4+ and CD8+ thymocytes in adult mice (39 +/- 10 x 10(6) in transgenic mice and 12 +/- 5 x 10(6) in age-matched controls). Furthermore, thymocyte export was disturbed.     

Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1.

We report the identification of mutations in lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) genes in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17. Linkage disequilibrium analysis of six families affected by NCIE permitted us to reduce a recently reported interval of 8.4 cM on chromosome 17p13.1 to a 600 kb region around the marker D17S1796, which contains LOX genes. LOX products have long been implicated in skin disorders. Two point mutations and one deletion were found in ALOXE3 and three point mutations were found in ALOX12B in these consanguineous families from the Mediterranean basin. ALOXE3 and ALOX12B are two genes which are physically linked and functionally related. They are separated by 38 kb, have one more exon than the other LOX genes and are mainly expressed in epithelial cells including keratinocytes. Although the main substrate(s) of the two enzymes is (are) still unknown, the products of ALOX12B obtained in experimental systems have been demonstrated to be of R-chirality. It seems likely that the product of one of these enzymes may be the substrate of the other, and that they belong to the same metabolic pathway.     

Monosomy 9q and trisomy 16q in a case of congenital solitary infantile myofibromatosis

Although infantile myofibromatosis (IM) is the most common fibrous proliferation of infancy, many aspects of this benign lesion have not been explored. IM histogenesis is still poorly understood, despite immunohistochemical staining and ultrastructural features that suggest a myofibroblastic origin. IM diagnosis is often made difficult by the predominance of small primitive spindle cells over myofibrobasts and the presence of intravascular growth. Genetic information is scarce, with only one karyotyped case. Here we describe a case of solitary IM discovered at birth in an otherwise healthy girl. The tumor was well circumscribed, arranged in nodules and made up of ovoid cells without atypia, in a myxoid background. Immunohistochemical evaluation indicated a myofibroblastic differentiation. The cytogenetic and fluorescence in situ hybridization analyses revealed an abnormal chromosome 9, derived from an unbalanced whole-arm translocation between chromosomes 9 and 16. On both chromosomes, the breakpoints were located in the pericentric heterochromatic region. This clonal abnormality has not been reported in other tumors and is different from the chromosome 6q deletion reported in the single previous reported IM karyotype.     

Mantle cell lymphoma, in leukaemic phase with prominent splenomegaly. A report of eight cases with similar clinical presentation and aggressive outcome

Mantle cell lymphoma (MCL) is a well-defined peripheral B-cell lymphoma usually diagnosed upon peripheral lymph node biopsy. We report eight cases of peripheral B-cell leukaemia that demonstrate presumptive evidence of mantle cell characteristics. The patients had a median age of 68.5 years, and five were male. All presented with an enlarged spleen without any peripheral lymphadenopathies, and they were leukaemic at presentation (median lymphocytosis, 38x10(9)/l). Morphological diagnosis of MCL was very difficult in five cases but easier in three because we were able to analyse either pre- or post-mortem lymph nodes and spleen. The immunophenotype of blood lymphocytosis using flow cytometry, the presence of a t(11;14)(q13;q32) and a cyclin D1 expression by leukaemic cells all fit with the diagnosis of MCL. All patients progressed and died with a median overall survival of 8 months. Multifocal areas of transformation in blastoid or large cell variants were observed in the three autopsied patients. In summary, one should consider the diagnosis of MCL at presentation in leukaemic phase even in the absence of peripheral adenopathies.     

Emerging patterns of cardiac conduction in the chick embryo: waveform analysis with photodiode array-based optical imaging.

Major difficulties investigating the developing cardiac conduction system stem from that the embryonic heart is extremely small (< 2 mm) and cardiac activation is relatively rapid (< 8 msec). The objective of this study was to investigate the electrophysiology of the embryonic chick cardiac conduction system at periseptation stages with a photodiode array-based detection method of optical mapping capable of high spatial and temporal resolution. Previous work indicated that, in chicken embryos, a switch occurs in ventricular activation pattern from immature base-to-apex to mature apex-to-base pattern at the time of ventricular septation. It was our aim to map activation in more detail to identify the active pathway or pathways of atrioventricular conduction at these particular stages. Analysis of preseptated hearts (n = 10) showed that the latest atrial activation took place just above the site of the earliest ventricular activation at the ventral left ventricular base. Analysis of postseptated hearts (n = 11) showed apex-to-base conduction consistent with activation through the maturing His-Purkinje system. Evaluation of hearts during septation revealed a gradual transition of ventricular activation patterns rather than an abrupt "switch." External pacing of preseptated hearts revealed significant slowing of interventricular conduction compared with spontaneous beats (spontaneous, 61.7 cm/sec +/- 9 cm/sec vs. paced, 36.5 cm/sec +/- 10 cm/sec). The more detailed mapping revealed that, before septation, the pattern of activation of the ventricular myocardium is consistent with direct atrial-ventricular myocardial connections at the left lateral atrioventricular junction; however, functional evidence for a preferential conduction pathway within the ventricles was present before septation.     

Hepatitis E in the south west of France in individuals who have never visited an endemic area

A total of 431 consecutive patients from the Midi Pyrenees area with acute hepatitis with unknown etiology in 2001-2002 were tested for the presence of immunoglobulin G-class (IgG) anti-hepatitis E virus (HEV) antibodies. Forty-six (10.7%) had anti-HEV IgG, and the results were questionable for a further 17 (3.9%). Real time PCR based on TaqMan detection was used to identify HEV genome fragments in the serum of patients with positive or questionable anti-HEV serology. HEV RNA was found in 25.4% of cases. All amplification products were sequenced and analyzed. Phylogenetic analysis revealed that all the strains were genotype 3. In conclusion, virological and epidemiological data indicate that genotype 3 viruses are circulating in the south west part of France (Midi-Pyrenees) in patients with acute hepatitis and who have not visited recently areas in which HEV is endemic.     

"Hemicrania continua": The first bilateral case?

The patient reported had had a continuous headache involving the whole skull for 7 years. Many drugs had failed to relieve the pain, but with indomethacin the headache completely disappeared within 3 days. Nine months later the treatment was discontinued without any relapse. This variety of headache, not previously reported, was quite similar to the "hemicrania continua" except for its localization.