Detection of a Specific Inhibitor of Interleukin 1 in Sera of UVB-Treated Mice

It was recently demonstrated that murine keratinocytes upon irradiation with ultraviolet (UV) light release an immunosuppressive cytokine which blocks the biological activity of interleukin 1 (IL 1). This epidermal cell derived inhibitor (EC-contra IL 1) exhibits a molecular weight of 40 kD and a pI of approximately 9.0. EC-contra IL 1 in vivo possibly may penetrate through the basal lamina and subsequently cause systemic immunosuppression following UV-exposure. In the present study, we tested whether EC-contra IL 1 can also be detected in vivo. Serum samples obtained from total body UV-exposed mice were subjected to HPLC gel filtration and tested for IL 1 inhibitory activity. While a non-specific high molecular weight (300 kD) suppressor factor was detected in sera of both UV-exposed and sham treated control mice, a specific IL 1 inhibitor exhibiting a molecular weight of 40 kD was observed only in sera of UV-exposed mice. This cytokine named serum-contra IL 1 was maximally released 24 h after UV-exposure, exhibited a pI of 9.0, and blocked the activity of natural as well as recombinant interleukin 1 in a dose dependent manner. Serum-contra IL 1 did not suppress interleukin 2 or interleukin 3 and did not inhibit spontaneous cell proliferation. The present biochemical and biologic data suggest that serum-contra IL 1 and EC-contra IL 1 appear to be closely related if not identical. These observations therefore indicate that keratinocytes upon UV-irradiation in vivo release EC-contra IL 1 which may at least partly be responsible for the immunosuppression following UV-exposure

The microbiome in patients with atopic dermatitis.

As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies

Human Granulocyte-Macrophage Colony Stimulating Factor: An Effective Direct Activator of Human Polymorphonuclear Neutrophilic Granulocytes

Granulocyet-macrophage colony-stimulating factor (GM-CSF) was shown to modulate different granulocyte functions. In the present study we investigated the effect of purified and recombinant human GM-CSF, particularly on the oxidative metabolism of isolated human granulocytes. In addition, ultrastructural changes upon stimulation were evaluated. For detection of granulocyte activation the following assay systems were used: 1) lucigenin-dependent chemiluminescence (CL),2) superoxide-dismutase (SOD) inhibitable cytochrome C-reduction (superoxide),3) horseradish peroxidase-mediated oxidation of phenol red (hydrogen peroxide),4) release of myeloperoxidase, 5) ultrastructural detection of hydrogen peroxide-production, and 6) scanning and transmission electron microscopy (SEM and TEM, respectively). A significant CL response was seen upon stimulation with recombinant human GM-CSF at concentrations ranging from 1 to 103 U/ml. The CL response started within 5-10 min with a maximum at 60 – 90 min and lasted more than 3 h. Thereafter granulocytes were completely deactivated to restimulation with the same mediator and with Tumor Necrosis Factor, but respondend to other triggers of the oxidative burst, whereas the response to f-met-leu-phe was significantly increased, The CL signal was completely blocked by an antiserum to GM-CSF. Moreover, the response was significantly inhibited by SOD and D-mannitol, suggesting the involvement of distinct reactive oxygen species (ROS) in generating the CL response. Significant amounts of superoxide were detected within 180 min after stimulation with GM-CSF, whereas, release of hydrogen peroxide and peroxidase were only minimal as shown by functional and ultrastructural assays. Activation of granulocytes could be visualized by SEM and TEM. GM-CSF stimulated cells showed an increased adherence to the substratum developing polarized filopodia and an increased number of intercellular vesicles within 30 min after addition of the stimulus. The results clearly demonstrate that GM-CSF directly stimulates granulocytes and, particularly, their oxidative metabolism. Therefore, GM-CSF which is probably released by epidermal cells appears to be a candidate for neutrophil activation in the skin, and thereby may play a crucial role in inflammatory skin diseases

The 3-dimensional architecture of the Upsilon Andromedae planetary system

The Upsilon Andromedae system is the first exoplanetary system to have the relative inclination of two planets' orbital planes directly measured, and therefore offers our first window into the 3-dimensional configurations of planetary systems. We present, for the first time, full 3-dimensional, dynamically stable configurations for the 3 planets of the system consistent with all observational constraints. While the outer 2 planets, c and d, are inclined by about 30 degrees, the inner planet's orbital plane has not been detected. We use N-body simulations to search for stable 3-planet configurations that are consistent with the combined radial velocity and astrometric solution. We find that only 10 trials out of 1000 are robustly stable on 100 Myr timescales, or about 8 billion orbits of planet b. Planet b's orbit must lie near the invariable plane of planets c and d, but can be either prograde or retrograde. These solutions predict b's mass is in the range 2 - 9 $M_{Jup}$ and has an inclination angle from the sky plane of less than 25 degrees. Combined with brightness variations in the combined star/planet light curve ("phase curve"), our results imply that planet b's radius is about 1.8 $R_{Jup}$, relatively large for a planet of its age. However, the eccentricity of b in several of our stable solutions reaches values greater than 0.1, generating upwards of $10^{19}$ watts in the interior of the planet via tidal dissipation, possibly inflating the radius to an amount consistent with phase curve observations.Comment: 17 pages, 10 figures, accepted for publication in ApJ; revised statement in Section 1.1, references added, results unchange

Older Veteran Digital Disparities: Examining the Potential for Solutions Within Social Networks

BACKGROUND: Older adults typically have less access to the Internet than other age groups, and older Veterans may use the Internet even less due to economic and geographic reasons. OBJECTIVE: To explore solutions to this problem, our study examined older Veterans\u27 reported ability to access technology through their close social ties. METHODS: Data were collected via mail survey from a sample of Veterans aged 65 years and older (N=266). RESULTS: Nearly half (44.0%, 117/266) of the sample reported having no Internet access. Yet, among those without current access, older Veterans reported having a median of 5 (IQR 7) close social ties with home Internet access. These older Veterans also reported that they would feel comfortable asking a median of 2 (IQR 4) social ties for help to access the Internet, and that a median of 2 (IQR 4) social ties would directly access the Internet for the older Veteran to help with health management. CONCLUSIONS: Findings suggest that even older Veterans without current Internet access have at least two social ties with home Internet who could be called upon for technology support. Thus, older Veterans may be willing to call upon these surrogate seekers for technology assistance and support in health management. This has implications for the digital divide, technology design, and health care policy