Influence of extracellular matrix proteins on the development of cultured human dendritic cells

The development of dendritic cells (DC) is still only partly understood. Recently established culture systems using CD34+ cells or monocytes as precursor cells for the generation of DC indicate the necessity of pro-inflammatory cytokines for their development. In vivo the contact to other cells or to the proteins of the extracellular matrix might also be essential for their development. In our experiments we used granulocyte-macrophage colony-stimulating factor- and IL-4-treated human monocytes as precursor cells to investigate the interaction of DC at different maturation stages with the matrix proteins fibronectin, collagen type I and collagen type IV. We demonstrate a strong beta1-integrin-mediated adherence of immature DC to fibronectin that is lost completely during maturation. The binding to collagen type I was less strong but induced a maturation of the precursor cells. After 3 days of culture on this protein, the cells showed all features of fully matured DC such as expression of CD83 and an excellent allostimulatory capacity. The reason for this effect was shown to be the induction of TNF-alpha production by the DC themselves. In contrast to the adhesion to fibronectin, the maturation and the cytokine production of DC induced by collagen type I could not be inhibited by blocking of beta1-integrins. These results indicate that proteins of the extracellular matrix play an important role in the development and function of human DC.     

Adjuvant therapy of pemphigus vulgaris and pemphigus foliaceus with intravenous immunoglobulins]

Many changes have occurred in the technology used to acquire dental images. Most of the research has been directed to reducing radiation to the patient while maintaining excellent diagnostic quality. With the introduction of computer technology and monitors, the patient is exposed to less radiation while diagnostic capabilities for the dental practitioner are enhanced. When this exciting, emerging technology is more fully utilized in practice, there will be great benefits to the patient and the dental profession alike.     

Spc98p directs the yeast gamma-tubulin complex into the nucleus and is subject to cell cycle-dependent phosphorylation on the nuclear side of the spindle pole body

In the yeast Saccharomyces cerevisiae, microtubules are organized by the spindle pole body (SPB), which is embedded in the nuclear envelope. Microtubule organization requires the gamma-tubulin complex containing the gamma-tubulin Tub4p, Spc98p, and Spc97p. The Tub4p complex is associated with cytoplasmic and nuclear substructures of the SPB, which organize the cytoplasmic and nuclear microtubules. Here we present evidence that the Tub4p complex assembles in the cytoplasm and then either binds to the cytoplasmic side of the SPB or is imported into the nucleus followed by binding to the nuclear side of the SPB. Nuclear import of the Tub4p complex is mediated by the essential nuclear localization sequence of Spc98p. Our studies also indicate that Spc98p in the Tub4p complex is phosphorylated at the nuclear, but not at the cytoplasmic, side of the SPB. This phosphorylation is cell cycle dependent and occurs after SPB duplication and nucleation of microtubules by the new SPB and therefore may have a role in mitotic spindle function. In addition, activation of the mitotic checkpoint stimulates Spc98p phosphorylation. The kinase Mps1p, which functions in SPB duplication and mitotic checkpoint control, seems to be involved in Spc98p phosphorylation. Our results also suggest that the nuclear and cytoplasmic Tub4p complexes are regulated differently.     

The type II IL-1 receptor interacts with the IL-1 receptor accessory protein: a novel mechanism of regulation of IL-1 responsiveness

IL-1 binds to two types of receptors on the cell membrane, of which only type I (IL-1RI) transduces signals in concert with the coreceptor IL-1 receptor accessory protein (IL-1RAcP) while type II (IL-1RII) allegedly functions solely as ligand sink and decoy receptor without participating in IL-1 signaling. To investigate the regulatory role of IL-1RII on IL-1 responsiveness, a chimeric receptor encompassing the extracellular and transmembrane portions of IL-1RII and the cytoplasmic signal-transducing domain of IL-1RI was transfected into two murine EL-4-derived sublines that do or do not express IL-1RAcP, respectively. The chimeric receptor was able to transduce the IL-1 signal and induce IL-2 production only in the cell line which expressed IL-1RAcP, suggesting effective interaction between the extracellular domains of IL-1RII and IL-1RAcP in the presence of IL-1. The physical association of ligated IL-1RII with IL-1RAcP was proven by crosslinking experiments with radio-iodinated IL-1 and subsequent immunoprecipitations in normal human B cells and in EL-4 D6/76 cells transiently cotransfected with IL-1RII and IL-1RAcP, respectively. Based on these findings, it is proposed that upon IL-1 binding IL-1RII can recruit IL-1RAcP into a nonfunctional trimeric complex and thus modulate IL-1 signaling by subtracting the coreceptor molecule from the signaling IL-1RI. In this novel mechanism of coreceptor competition, the ratio between IL-1RII and IL-1RI becomes the central factor in determining the IL-1 responsiveness of a cell and the availability of IL-1RAcP becomes limiting for effective IL-1 signaling.     

On the use of a conical cornucopia antenna to reduce EMI

The wide-angle radiation form a prime-fed parabolic reflector antenna and the associated EMI (electromagnetic interference) it produces can be greatly reduced by constructing the antenna in the form of an absorber-lined conical cornucopia (CC). Measured RPEs (radiation pattern envelopes) are inspected for the case where all antennas have about a 10-ft diameter and 43-dBi gain at 6 GHz and typify the type of WAR (wide-angle radiation)-RPE improvement achievable if scaled to other bands/sizes. It is shown that the CC's RPEs for angles from about 10 full half-power beamwidths (here 10°) and beyond, and most especially from about 30 full half-power beamwidths (here 30°) and beyond, are vastly superior to those of either the standard or improved (UHX/UMX) parabolic dishes. Indeed, it is seen that the CC's RPE levels are about 95 dB down from on axis for angles greater than about 90°. In other words, the CC's wide-angle RPE is about 40 dB lower than that of a standard parabolic-dish antenna of the same gain. These very low WAR levels then greatly mitigate the EMI to adjacent microwave routes in terrestrial radio relay applications     

On the leakage radiation from a circumferentially-slotted cylinderand its application to the EMI produced by TEM-coaxial rotaryjoints

The amount of leakage radiation, as well as the radiation pattern and its gain, produced by a complete 360° circumferential-narrow gap cut in a coaxial cable carrying a TEM mode is determined. Leakage levels for such a typical cable of approximately 26% are predicted to occur for gaps as small as about 0.0074λ. The former is substantiated by measurement on a ⅞" diameter coaxial cable of 50 Ω characteristic impedance operating at 2 GHz. Estimates of the EMI levels produced by typical coaxial choked-rotary joints (where the chokes significantly decrease the gap leakage) operating at high power levels are then given     

Copper is a Cofactor of the Formylglycine‐Generating Enzyme

Formylglycine‐generating enzyme (FGE) is an O₂‐utilizing oxidase that converts specific cysteine residues of client proteins to formylglycine. We show that Cu^I is an integral cofactor of this enzyme and binds with high affinity (K_D=of 10^?17 m ) to a pair of active‐site cysteines. These findings establish FGE as a novel type of copper enzyme.