Anti-neutrophil cytoplasmic antibody associated vasculitis of the brain and oral cavity: a case report.

We report a patient with a novel presentation of anti-neutrophil cytoplasmic antibody positive (ANCA+) vasculitis of the brain and oral mucosa. ANCA+ vasculitis of the brain is usually associated with pachymeningitis and hypophysitis, and there are no cases reported with simultaneous brain and oral mucosal involvement. A 35-year-old African Zambian man presented with headache and bleeding swollen gingiva. He was myeloperoxidase (MPO) antibody positive with cytoplasmic staining. His MRI showed stable small callosal, periventricular and subcortical white matter non-enhancing lesions, without change over 15 months-compatible with vasculitis. His gingival biopsy was consistent with vasculitis. His headache and oral lesions responded to oral corticosteroids and intravenous immunoglobulin which have induced clinical remission. Our patient expands the clinical syndrome of ANCA+ MPO+ C-type vasculitis of the central nervous system with headaches complicating cerebral vasculitis and oral mucosal involvement.

Novel cathelicidins in horse leukocytes(1).

Cathelicidins are precursors of defense peptides of the innate immunity and are widespread in mammals. Their structure comprises a conserved prepropiece and an antimicrobial domain that is structurally varied both intra- and inter-species. We investigated the complexity of the cathelicidin family in horse by a reverse transcription-PCR-based cloning strategy of myeloid mRNA and by Southern and Western analyses. Three novel cathelicidin sequences were deduced from bone marrow mRNA and designated equine cathelicidins eCATH-1, eCATH-2 and eCATH-3. Putative antimicrobial domains of 26, 27 and 40 residues with no significant sequence homology to other peptides were inferred at the C-terminus of the sequences. Southern analysis of genomic DNA using a probe based on the cathelicidin-conserved propiece revealed a polymorphic DNA region with several hybridization-positive fragments and suggested the presence of additional genes. A null eCATH-1 allele was also demonstrated with a frequency of 0.71 in the horse population analyzed and low amounts of eCATH-1-specific mRNA were found in myeloid cells of gene-positive animals. A Western analysis using antibodies to synthetic eCATH peptides revealed the presence of eCATH-2 and eCATH-3 propeptides, but not of eCATH-1-related polypeptides, in horse neutrophil granules and in the secretions of phorbol myristate acetate-stimulated neutrophils. These results thus suggest that eCATH-2 and eCATH-3 are functional genes, whereas eCATH-1 is unable to encode a polypeptide.

Primary effusion lymphoma cell lines harbouring human herpesvirus type-8.

Primary effusion lymphoma (PEL) is a novel lymphoma entity consistently infected by HHV-8 that occurs predominantly in immunodeficient patients and is characterized by liquid growth in the serous body cavities. In order to facilitate the understanding of PEL pathogenesis and histogenesis, we have established three PEL cell lines termed CRO-AP/2, CRO-AP/3 and CRO-AP/5. All cell lines have been derived from HIV positive homosexual men affected by PEL with (in the case of CRO-AP/2 and CRO-AP/5) or without (in the case of CRO-AP/3) a previous history of Kaposi's sarcoma. The cell lines are representative of both virologic variants of PEL, i.e. HHV-8+ EBV+ PEL (CRO-AP/2 and CRO-AP/5) and HHV-8+ EBV- PEL (CRO-AP/3). Morphologic and phenotypic features of CRO-AP/2, CRO-AP/3 and CRO-AP/5 are typical of PEL, and include morphology bridging immunoblastic and anaplastic features as well as an indeterminate (non B- non T-cell) phenotype. The B-cell nature of the cell lines is documented by the presence of rearranged immunoglobulin genes. The detailed analysis of the molecular and phenotypic features of CRO-AP/2, CRO-AP/3 and CRO-AP/5 has allowed the identification of recurrent chromosomal abnormalities of PEL and has contributed to the definition of PEL as a lymphoma of post-germinal center, pre-terminally differentiated B-cells.

Proliferation in HHV-8-positive primary effusion lymphomas is associated with expression of HHV-8 cyclin but independent of p27(kip1).

Primary effusion lymphoma (PEL) develops in immunodeficient patients, selectively localizes to the serous body cavities, and harbors infection by human herpesvirus type-8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus. HHV-8 encodes a viral (v)-cyclin homologous to cellular D-type cyclins, a class of positive cell-cycle regulators that are physiologically modulated by the p27(Kip1) cell cycle inhibitor. The aims of the present study were: 1) to establish the expression pattern of p27(Kip1) in PEL; and 2) to address the relationship between p27(Kip1) expression, proliferation index, and expression of cellular cyclin D1 and v-cyclin in PEL. Expression of p27(Kip1) was detected in all (n = 18) PEL samples analyzed by both immunocytochemistry and Western blot. All PELs displayed a high proliferation index as assessed by Ki-67 staining. Expression of cellular cyclin D1 was absent in all PELs tested, which conversely expressed (14 out of 14 samples) v-cyclin by immunocytochemistry and/or Western blot. In contrast to PELs, HHV-8-negative lymphomatous effusions secondary to a tissue-based lymphoma generally failed to express p27(Kip1). Overall, these data show that PELs consistently express p27(Kip1) protein despite the high proliferative rate of the lymphoma clone, suggesting that p27(Kip1) may be unable to drive cell-cycle arrest in PEL cells. The co-existence of p27(Kip1) expression and high proliferative index is a selective feature of PEL among lymphomas involving the serous body cavities, because lymphomatous effusions secondary to a tissue-based lymphoma generally display the inverse relationship between p27(Kip1) positivity and growth fraction observed in normal lymphoid tissues and in most other lymphomas. Expression of p27(Kip1) in PEL associates with expression of HHV-8 v-cyclin, but not of cellular cyclin D1. The fact that HHV-8 v-cyclin is resistant to p27(Kip1)-modulated inhibition, whereas cellular cyclin D1 is sensitive, may explain, at least in part, the co-existence of p27(Kip1) expression and high proliferative index observed in PEL.