Equine multisystemic eosinophilic epitheliotropic disease: a case report and review of literature.

CASE HISTORY: A 2-year-old Standardbred gelding presented with a history of fever over 1 week, anorexia and skin lesions on all four legs. The lesions were associated with severe pruritus and oedema, and there was no response to therapy. CLINICAL FINDINGS: The horse was in poor body condition, was lethargic and severely pruritic. Skin lesions consisted of diffuse alopecia and crusting of the distal extremities. Initially it was slightly febrile, but subsequently its temperature increased up to 40°C. Ten days after admission it developed profuse watery diarrhoea and the skin lesions progressed. Skin biopsies revealed superficial and deep perivascular dermatitis with lymphoplasmacytic and eosinophilic predominance. Based on the poor prognosis the horse was subject to euthanasia. PATHOLOGICAL FINDINGS: The most notable lesions included ulcerative gastritis, typhlitis and colitis with prominent oedema of the intestines, marked subcutaneous oedema and severe thickening of the large bile ducts. Histopathology showed marked eosinophilic and lymphoplasmacytic infiltration of various tissues including the skin, gastrointestinal tract, mesenteric lymph nodes, large bile ducts, pancreatic duct and kidney. Immunohistochemistry revealed a clear predominance of CD3-positive cells in the lymphocytic infiltrations. DIAGNOSIS: Based on the clinical findings and histopathology a diagnosis of multisystemic eosinophilic epitheliotropic disease (MEED) was made. CLINICAL RELEVANCE: Multisystemic eosinophilic epitheliotropic disease is rare in horses, and usually chronic. In the current case the horse showed an apparently acute onset with high fever and rapid clinical deterioration. A diagnosis of MEED should be considered in horses presenting with weight loss and skin lesions with or without fever. A final diagnosis is based on histological results of biopsy specimens from affected organs.

Hypercortisolism affects glomerular and tubular function in dogs.

Renal function was assessed in 25 dogs with Cushing's syndrome and in 12 healthy controls. Routine renal parameters and glomerular filtration rate (GFR) were measured and urinary biomarkers such as urinary albumin (uALB), urinary immunoglobulin G (uIgG), and urinary retinol-binding protein (uRBP) were assessed by ELISA. Urinary N-acetyl-ß-D-glucosaminidase activity (uNAG) was determined colorimetrically. All urinary markers were indexed to urinary creatinine concentration (c). Plasma exo- (Cl(exo)) and endo-iohexol (Cl(endo)) clearance were used to measure GFR. Based on a Mann-Whitney U test, urea and Cl(exo) did not differ, sCr was significantly lower, and UPC, uALB/c, uIgG/c, uRBP/c, uNAG/c and Cl(endo) were higher in the dogs with Cushing's syndrome when compared with controls. The findings indicate that glomerular and tubular function are both altered in dogs with Cushing's syndrome. Further longitudinal studies will be required to elucidate the pathogenesis of the changes in GFR.

Malassezia species isolated from the intermammary and preputial fossa areas of horses.

BACKGROUND: Malassezia-type yeasts previously have been observed on cytologic examination of the intermammary region of mares that presented with tail-head pruritus; topical antiyeast treatment resolved the pruritus. Further, Malassezia dermatitis has been observed in horses in intertriginous areas such as the udder and prepuce; the species of yeast was not confirmed. It is not known whether healthy mares or male horses can be carriers of this yeast in these body areas. HYPOTHESIS: Malassezia spp. are present in the intermammary region in healthy mares and the preputial fossa in healthy geldings. ANIMALS: Eleven healthy horses (5 mares and 6 geldings). METHODS: Samples of surface material were taken digitally from the intermammary area of 5 mares and the preputial fossa region of 6 geldings. The samples were examined cytologically and were cultured on modified Sabouraud's dextrose agar. The DNA from yeast colonies grown on the agar was extracted, and samples were assayed using fungal generic polymerase chain reaction (PCR) analysis. Amplicons with positive PCR results were sequenced and compared with sequences in the BLAST database search program. RESULTS: Of 44 attempts at culture, 5 yielded a species identified as Malassezia equi, and 2 yielded M slooffiae. In contrast, of 44 cytologic examinations, yeasts with the morphology of Malassezia spp. were seen in 40 samples. CONCLUSIONS AND CLINICAL IMPORTANCE: Due to its presence in healthy horses, finding of Malassezia-type yeast on cytologic examination may not incriminate it as a pathogen. Despite difficulty in culturing, cytologic examination was an effective tool to rapidly demonstrate the organism.

Plasmacytoid monocytes/T cells: a dendritic cell lineage?

Plasmacytoid monocytes/T cells were first described in 1958, yet their origin and function have remained enigmatic. Recently a series of publications brought these cells to the forefront of immunological research. Indeed, plasmacytoid monocytes/T-cells contain natural type-I interferon producing cells and can differentiate in vitro into dendritic cells (DC). It has been proposed that plasmacytoid monocytes/T-cells represent a distinct lineage of cells whose fate it is to differentiate into dendritic cells. Herein we will review recent advances in our understanding of plasmacytoid monocytes/T cells and highlight arguments in favor or against this lineage hypothesis. We propose that plasmacytoid monocytes/T cells represent a composite group of both myeloid and lymphoid early-committed cells that are characterized by their ability to differentiate in vitro into DC.

Derivation of dendritic cells from myeloid and lymphoid precursors.

The antigen presenting dendritic cells (DC) found in mouse and human lymphoid tissues are heterogeneous. Several subsets of mature DC have been described and these may correspond to distinct lineages. In this review, we present evidence obtained from a series of studies on the lineage origin of DC. This evidence points to the existence of at least three pathways for DC development, namely one from myeloid progenitors, a second from lymphoid progenitors and the third for Langerhans cells from precursors whose relationship to myeloid or lymphoid cell types is not yet clearly defined.

Human thymus contains 2 distinct dendritic cell populations.

In this study, 2 distinct populations of mature dendritic cells (DCs) were identified in the human thymus. The major population is CD11b-, CD11c+, and CD45RO(low) and does not express myeloid-related markers. It displays all the characteristics of mature DCs with a typical dendritic morphology, high surface levels of HLA-DR, CD40, CD83, and CD86, and expression of DC-lysosome-associated membrane glycoprotein messenger RNA (mRNA). In addition, CD11b- thymic DCs do not express macrophage inflammatory protein-1alpha (MIP-1alpha) mRNA, but express thymus-expressed chemokine (TECK) mRNA and are able to secrete bioactive interleukin 12 (IL-12) upon stimulation. In contrast, the minor and variable thymic DC population is CD11b+, CD11c(high), and CD45RO(high) and comprises CD83+CD14- mature and CD83- CD14+ immature DCs. It expresses macrophage-colony stimulating factor receptor, MIP-1alpha mRNA and high amounts of decysin mRNA after CD40 activation, but does not express TECK and is a weak bioactive IL-12 producer. Also identified were the IL-3Ralpha(high) plasmacytoid cells, which are present in the thymic cortex and medulla. Upon culture with IL-3, granulocyte/macrophage-colony stimulating factor, and CD40 ligand, the plasmacytoid cells can adopt a phenotype resembling that of freshly isolated CD11b- thymic DCs. However, these plasmacytoid-derived DCs fail to secrete bioactive IL-12; therefore, conclusions cannot be made about a direct relation between thymic plasmacytoid cells and CD11b- DCs. Whereas CD11b+ thymic DCs appear to be related to tonsillar germinal-center DCs, the major CD11b- IL-12-secreting human thymus DC population has similarities to mouse CD11b- CD8+ DCs.

Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells.

Interleukin (IL)-12 may be secreted as a bioactive T helper type 1 (Th1) cell-inducing heterodimer, as a monomer, or as an antagonistic homodimer. We analyzed the IL-12 produced by mouse splenic dendritic cells (DCs), human thymic DCs, and cultured human monocyte-derived DCs. IL-12 production required both a microbial or T cell-derived stimulus and an appropriate cytokine milieu. The different IL-12 forms were differentially regulated by the cytokines present rather than the stimulus used. IL-4 alone or together with granulocyte/macrophage colony-stimulating factor or interferon gamma effectively enhanced the production of the bioactive heterodimer and selectively reduced the antagonistic homodimer of IL-12. Therefore, IL-4, the major Th2-driving cytokine, provides a negative feedback causing DCs to produce the major Th1-inducing cytokine, bioactive IL-12.

Dual action of the active oxygen species during plant stress responses.

Adaptation to environmental changes is crucial for plant growth and survival. However, the molecular and biochemical mechanisms of adaptation are still poorly understood and the signaling pathways involved remain elusive. Active oxygen species (AOS) have been proposed as a central component of plant adaptation to both biotic and abiotic stresses. Under such conditions, AOS may play two very different roles: exacerbating damage or signaling the activation of defense responses. Such a dual function was first described in pathogenesis but has also recently been demonstrated during several abiotic stress responses. To allow for these different roles, cellular levels of AOS must be tightly controlled. The numerous AOS sources and a complex system of oxidant scavengers provide the flexibility necessary for these functions. This review discusses the dual action of AOS during plant stress responses.

Dendritic cell origins: puzzles and paradoxes.

In the present review, a series of studies on the origins of dendritic cells of mice and humans are summarized. Several subsets of mature dendritic cells found in vivo are described and these may correspond to distinct lineages. There is evidence that some dendritic cells are myeloid-derived and that others are lymphoid-derived. The different ways of generating dendritic cells are examined and an attempt to reconcile the differences seen using mouse and human culture models is made. The particular case of Langerhans cells is discussed and an historical overview of the biology of the plasmacytoid T cells, which may represent a distinct 'lymphoid-related' dendritic cell lineage, is given. It is concluded that three or four different pathways lead to the development of different subtypes of dendritic cells.

A novel lysosome-associated membrane glycoprotein, DC-LAMP, induced upon DC maturation, is transiently expressed in MHC class II compartment.

We have identified a novel lysosome-associated membrane glycoprotein localized on chromosome 3q26.3-q27, DC-LAMP, which is homologous to CD68. DC-LAMP mRNA is present only in lymphoid organs and DC. A specific MAb detects the protein exclusively in interdigitating dendritic cells. Expression of DC-LAMP increases progressively during in vitro DC differentiation, but sharply upon activation with LPS, TNFalpha, or CD40L. Confocal microscopy confirmed the lysosomal distribution of the protein. Furthermore, DC-LAMP was found in the MHC class II compartment immediately before the translocation of MHC class II molecules to the cell surface, after which it concentrates into perinuclear lysosomes. This suggests that DC-LAMP might change the lysosome function after the transfer of peptide-MHC class II molecules to the surface of DC.

Human dendritic cells skew isotype switching of CD40-activated naive B cells towards IgA1 and IgA2.

Within T cell-rich areas of secondary lymphoid organs, interdigitating dendritic cells recruit antigen-specific T cells that then induce B cells to secrete Igs. This study investigates the possible role(s) of dendritic cells in the regulation of human B cell responses. In the absence of exogenous cytokines, in vitro generated dendritic cells (referred to as Dendritic Langerhans cells, D-Lc) induced surface IgA expression on approximately 10% of CD40-activated naive sIgD+ B cells. In the presence of IL-10 and TGF-beta, a combination of cytokines previously identified for its capacity to induce IgA switch, D-Lc strongly potentiated the induction of sIgA on CD40-activated naive B cells from 5% to 40-50%. D-Lc alone did not induce the secretion of IgA by CD40-activated naive B cells, which required further addition of IL-10. Furthermore, D-Lc skewed towards the IgA isotype at the expense of IgG, the Ig production of CD40-activated naive B cells cultured in the presence of IL-10 and TGF-beta. Importantly, under these culture conditions, both IgA1 and IgA2 were detected. In the presence of IL-10, secretion of IgA2 by CD40-activated naive B cells could be detected only in response to D-Lc and was further enhanced by TGF-beta. Collectively, these results suggest that in addition to activating T cells in the extrafollicular areas of secondary lymphoid organs, human D-Lc also directly modulate T cell-dependent B cell growth and differentiation, by inducing the IgA isotype switch.

[Nicotine and worsening myasthenia]. / Nicotine et aggravation de la myasthénie.

We report a case of myasthenia gravis worsened by a nicotine transdermal system, in a man who usually was smoking fourty cigarettes per day without any worsening of his symptomatology. He noted an increased bilateral ptosis, total ophtalmoplegia, difficulty in chewing and generalized weakness two hours after application of a nicotine transdermal system, the symptoms improving after he removed it. Cholinergic receptors involved in myasthenia gravis are nicotinergic, and their number at the neuromuscular junction is reduced in myasthenia gravis. That leads to a "functional overdosage" after application of the nicotine transdermal system similar to the cholinergic crisis. This case can be compared with myasthenia syndromes described during the Second World War in tobacco chewers without any muscle impairment.