Localization of Basic Fibroblast Growth Factor mRNA in Melanocytic Lesions by In Situ Hybridization

Basic fibroblast growth factor (bFGF) is a mitogen for normal human melanocytes and keratinocytes in culture. Experiments in vitro suggest that keratinocytes supply bFGF to melanocytes through a paracrine mechanism and that the aberrant expression of bFGF in melanomas confers growth independence from bFGF-producing cells. To determine whether bFGF is expressed in vivo, we examined a series of benign and malignant melanocytic lesions in situ using bFGF riboprobes on tissue sections, and correlated bFGF expression with histologic phenotype. Seventeen melanocytic neoplasms were studied, including four common acquired nevi, four dysplastic nevi, four primary malignant melanomas, and five metastatic melanomas. Nevic cells in benign intradermal nevi showed low signal intensity (1+), whereas compound and dysplastic nevi showed 2+ to 3+ expression in the junctional nevic cell population and 1+ expression in the dermal nevic cell population. Melanocytes in primary melanomas had intermediate (2+) and those in metastatic melanomas had low (1+) levels of bFGF gene transcripts. Fibroblasts expressed high levels (3+) and epidermal and adnexal keratinocytes moderate (2+) levels of bFGF in all cases studied. Basic PGF expression in endothelial cells, known to produce and respond to this growth factor in vitro, was lower than that in the fibroblast and keratinocyte cell population and, in 10 of 17 cases, no bFGF mRNA was detectable. This study shows that bFGF is expressed in nevomelanocytes in vivo in all melanocytic lesions studied and thus cannot be used as a marker for transformation. The presence of bFGF gene transcripts in the various dermal cell types and in keratinocytes suggests that it may act as an autocrine and paracrine growth factor in regulating cellular proliferation in the skin

Position-momentum local realism violation of the Hardy type

We show that it is, in principle, possible to perform local realism violating experiments of the Hardy type in which only position and momentum measurements are made on two particles emanating from a common source. In the optical domain, homodyne detection of the in-phase and out-of-phase amplitude components of an electromagnetic field is analogous to position and momentum measurement. Hence, local realism violations of the Hardy type are possible in optical systems employing only homodyne detection.Comment: 10 pages, no figures, to be published in Physical Review

Eosinophils downregulate lung alloimmunity by decreasing TCR signal transduction

Despite the accepted notion that granulocytes play a universally destructive role in organ and tissue grafts, it has been recently described that eosinophils can facilitate immunosuppression-mediated acceptance of murine lung allografts. The mechanism of eosinophil-mediated tolerance, or their role in regulating alloimmune responses in the absence of immunosuppression, remains unknown. Using lung transplants in a fully MHC-mismatched BALB/c (H2d) to C57BL/6 (H2b) strain combination, we demonstrate that eosinophils downregulate T cell-mediated immune responses and play a tolerogenic role even in the absence of immunosuppression. We further show that such downregulation depends on PD-L1/PD-1-mediated synapse formation between eosinophils and T cells. We also demonstrate that eosinophils suppress T lymphocyte responses through the inhibition of T cell receptor/CD3 (TCR/CD3) subunit association and signal transduction in an inducible NOS-dependent manner. Increasing local eosinophil concentration, through administration of intratracheal eotaxin and IL-5, can ameliorate alloimmune responses in the lung allograft. Thus, our data indicate that eosinophil mobilization may be utilized as a novel means of lung allograft-specific immunosuppression

Hadronic properties of the S_{11}(1535) studied by electroproduction off the deuteron

Properties of excited baryonic states are investigated in the context of electroproduction of baryon resonances off the deuteron. In particular, the hadronic radii and the compositeness of baryon resonances are studied for kinematic situations in which their hadronic reinteraction is the dominant contribution. Specifically, we study the reaction $d(e,e'S_{11})N$ at $Q^2\ge 1 GeV^2$ for kinematics in which the produced hadronic state reinteracts predominantly with the spectator nucleon. A comparison of constituent quark model and effective chiral Lagrangian calculations of the $S_{11}$ shows substantial sensitivity to the structure of the produced resonance.Comment: 24 pages, 5 figure