Sensitization to self (virus) antigen by in situ expression of murine interferon-gamma.

Autoimmune disease results from inflammatory destruction of tissues by aberrant self-reactive lymphocytes. We studied the autoimmune potential of T lymphocytes immunologically ignorant of viral antigens acting as self antigens and whether the host defense molecule IFN-gamma could stimulate these cells to cytotoxic competency. For this purpose, we produced double transgenic mice expressing pancreatic IFN-gamma as well as lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) or glycoprotein (GP) antigen. 100% of the NP+/IFN-gamma+ mice became diabetic before 2 mo of age, while none of the NP single transgenic littermates and only 10% of IFN-gamma single transgenic littermates did. Strikingly, NP+/IFN-gamma+ mice spontaneously developed cytotoxic T lymphocyte activity on LCMV-infected targets and vaccinia virus-NP-infected ones without prior LCMV infection but NP+/IFN-gamma- mice did not, which indicates specific sensitization to the viral antigen by IFN-gamma. These results suggest that lymphocytes ignorant of self antigens can be activated by IFN-gamma released after immunologic stimulation such as viral infection. This mechanism may account for the loss of apparent tolerance to self antigens in autoimmune diseases such as insulin-dependent diabetes mellitus

Xenopus: An alternative model system for identifying muco-active agents

The airway epithelium in human plays a central role as the first line of defense against environmental contaminants. Most respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, and respiratory infections, disturb normal muco-ciliary functions by stimulating the hypersecretion of mucus. Several muco-active agents have been used to treat hypersecretion symptoms in patients. Current muco-active reagents control mucus secretion by modulating either airway inflammation, cholinergic parasympathetic nerve activities or by reducing the viscosity by cleaving crosslinking in mucin and digesting DNAs in mucus. However, none of the current medication regulates mucus secretion by directly targeting airway goblet cells. The major hurdle for screening potential muco-active agents that directly affect the goblet cells, is the unavailability of in vivo model systems suitable for high-throughput screening. In this study, we developed a high-throughput in vivo model system for identifying muco-active reagents using Xenopus laevis embryos. We tested mucus secretion under various conditions and developed a screening strategy to identify potential muco-regulators. Using this novel screening technique, we identified narasin as a potential muco-regulator. Narasin treatment of developing Xenopus embryos significantly reduced mucus secretion. Furthermore, the human lung epithelial cell line, Calu-3, responded similarly to narasin treatment, validating our technique for discovering muco-active reagent

Molecular cloning and expression of a novel human cDNA related to the diazepam binding inhibitor

AbstractIn order to isolate the unidentified autoantigens in autoimmune diabetes, a human pancreatic islet cDNA library was constructed and screened with the sera from the diabetic patients. From the library screening, one clone (DRS-1) that strongly reacted with the sera was isolated. Subsequent sequence analysis revealed that the clone was a novel cDNA related to the diazepam binding inhibitor. DRS-1 was expressed in most tissues including liver, lung, tonsil, and thymus, in addition to pancreatic islets. DRS-1 was in vitro translated and the recombinant DRS-1 protein was expressed in Escherichia coli and purified. The size of the in vitro translated or bacterially expressed DRS-1 protein was in agreement with the conceptually translated polypeptide of DRS-1 cDNA. Further studies are required to test whether or not DRS-1 is a new autoantigen in autoimmune diabetes

Redak slučaj metastatskog spermatocitnog tumora kod psa bez sarkomatoznih i anaplastičnih promena

Spermatocytic tumor is a rare testicular tumor, which is originated from gonocytes. It is characterized by the histological feature of tripartite which is composed of large, medium, and lymphocyte-like small cells. It is well-known that spematocytic tumor is benign, thus a good prognosis is expected after simple resection. Metastatic spermatocytic tumor is extremely rare and usually accompanied by histological variants including sarcomatous changes and anaplastic variants. In this case, however, we report a canine metastatic spermatocytic tumor without prominent sarcomatous changes and anaplastic variants. The mass was composed of three kinds of cells including large, medium, and small cells with high pleomorphism. The neoplastic cells had an indistinct cytoplasmic border and mitotic figures were frequently observed. The primary spermatocytic tumor metastasized to the abdominal organs one month after the resection, and the dog died 13 months after the surgery. Thus, careful follow-up is recommended after surgical resection of canine spermatocytic tumor even though metastasis in spermatocytic tumors is rare.Spermatocitni tumor je redak tumor testisa, koji potiče od gonocita. Karakteriše ga histološki nalaz tri morfološka tipa ćelija, a sastoji se od velikih, srednjih i limfocitima sličnih malih ć elija. Dobro je poznato da je spermatocitni tumor benignog ponašanja pa se očekuje dobra prognoza nakon jednostavne resekcije. Metastatski spermatocitni tumor izuzetno je redak i obično je prać en histološkim varijacijama, uključujuć i sarkomatozne i anaplastične promene. U ovom slučaju, međutim, opisan je metastatski spermatocitni tumor bez izraženih sarkomatoznih promena i anaplastičnih varijanti. Masa se sastojala od tri vrste ć elija, uključujuć i velike, srednje i male ć elije sa visokim pleomorfi zmom. Neoplastične ć elije su imale nejasnu citoplazmatsku granicu i često su primeć ene mitotičke fi gure. Primarni spermatocitni tumor metastazirao je na trbušne organe mesec dana nakon resekcije, a pas je uginuo 13 meseci nakon operacije. Stoga se preporučuje pažljivo prać enje nakon hirurške resekcije spermatocitnog tumora mada su metastaze u spermatocitnim tumorima retke

Platelet-activating Factor–mediated NF-κB Dependency of a Late Anaphylactic Reaction

Anaphylaxis is a life-threatening systemic allergic reaction with the potential for a recurrent or biphasic pattern. Despite an incidence of biphasic reaction between 5 and 20%, the molecular mechanism for the reaction is unknown. Using a murine model of penicillin V–induced systemic anaphylaxis, we show an autoregulatory cascade of biphasic anaphylactic reactions. Induction of anaphylaxis caused a rapid increase in circulating platelet-activating factor (PAF) levels. In turn, the elevated PAF contributes to the early phase of anaphylaxis as well as the subsequent activation of the nuclear factor (NF)-κB, a crucial transcription factor regulating the expression of many proinflammatory cytokines and immunoregulatory molecules. The induction of NF-κB activity is accompanied by TNF-α production, which, in turn, promotes late phase PAF synthesis. This secondary wave of PAF production leads eventually to the late phase of anaphylactic reactions. Mast cells do not appear to be required for development of the late phase anaphylaxis. Together, this work reveals the first mechanistic basis for biphasic anaphylactic reactions and provides possible therapeutic strategies for human anaphylaxis