Comparative study of gp130 cytokine effects on corticotroph AtT-20 cells - Redundancy or specificity of neuroimmunoendocrine modulators?

Objective: This comparative in vitro study examined the effects of all known gp130 cytokines on murine corticotroph AtT-20 cell function. Methods: Cytokines were tested at equimolar concentrations from 0.078 to 10 nM. Tyrosine phosphorylation of the signal transducer and activator of transcription ( STAT) 3 and STAT1, the STAT-dependent suppressor of cytokine signaling (SOCS)-3 promoter activity, SOCS-3 gene expression, STAT-dependent POMC promoter activity and adrenocorticotropic hormone ( ACTH) secretion were determined. Results: Leukemia inhibitory factor (LIF), human oncostatin M (OSM) and cardiotrophin (CT)-1 (LIFR/gp130 ligands), as well as ciliary neurotrophic factor ( CNTF) and novel neurotrophin1/B-cell stimulating factor-3 (CNTFRalpha/LIFR/gp130 ligands) are potent stimuli of corticotroph cells in vitro. In comparison, interleukin (IL)-6 (IL-6R/gp130 ligand) and IL-11 (IL-11R/gp130 ligand) exhibited only modest direct effects on corticotrophs, while murine OSM (OSMR/gp130 ligand) showed no effect. Conclusion: (i) CNTFR complex ligands are potent stimuli of corticotroph function, comparable to LIFR complex ligands; (ii) IL-6 and IL-11 are relatively weak direct stimuli of corticotroph function; (iii) differential effects of human and murine OSM suggest that LIFR/gp130 (OSMR type I) but not OSMR/gp130 (OSMR type II) are involved in corticotroph signaling. (iv) CT-1 has the hitherto unknown ability to stimulate corticotroph function, and (v) despite redundant immuno-neuroendocrine effects of different gp130 cytokines, corticotroph cells are preferably activated through the LIFR and CNTFR complexes. Copyright (C) 2004 S. Karger AG, Basel

Marine forearc structure of eastern Java and its role in the 1994 Java tsunami earthquake

We resolve a previously unrecognized shallow subducting seamount from a re-processed multichannel seismic depth image crossing the 1994 M7.8 Java tsunami earthquake slip area. Seamount subduction is related to the uplift of the overriding plate by lateral shortening and vertical thickening, causing pronounced back-thrusting at the landward slope of the forearc high and the formation of splay faults branching off the landward flank of the subducting seamount. The location of the seamount in relation to the 1994 earthquake hypocentre and its co-seismic slip model suggests that the seamount acted as a seismic barrier to the up-dip co-seismic rupture propagation of this moderate size earthquake. The wrapping of the co-seismic slip contours around the seamount indicates that it diverted rupture propagation, documenting the control of forearc structures on seismic rupture

Separate Universes Do Not Constrain Primordial Black Hole Formation

Carr and Hawking showed that the proper size of a spherical overdense region surrounded by a flat FRW universe cannot be arbitrarily large as otherwise the region would close up on itself and become a separate universe. From this result they derived a condition connecting size and density of the overdense region ensuring that it is part of our universe. Carr used this condition to obtain an upper bound for the density fluctuation amplitude with the property that for smaller amplitudes the formation of a primordial black hole is possible, while larger ones indicate a separate universe. In contrast, we find that the appearance of a maximum is not a consequence of avoiding separate universes but arises naturally from the geometry of the chosen slicing. Using instead of density a volume fluctuation variable reveals that a fluctuation is a separate universe iff this variable diverges on superhorizon scales. Hence Carr's and Hawking's condition does not pose a physical constraint on density fluctuations. The dynamics of primordial black hole formation with an initial curvature fluctuation amplitude larger than the one corresponding to the maximum density fluctuation amplitude was previously not considered in detail and so we compare it to the well-known case where the amplitude is smaller by presenting embedding and conformal diagrams of both types in dust spacetimes.Comment: Updated version corresponds to the published version 10.1103/PhysRevD.83.124025, 22 pages, 22 figure

DC generation from peripheral blood mononuclear cells in patients with chronic myeloid leukemia: Influence of interferons on DC yield and functional properties

In Chronic Myeloid Leukemia (CML), standard treatment consists of modern tyrosine-kinase inhibitors (TKI). Nevertheless, there is evidence that immune responses against leukemia-associated antigens (LAA) may play an important role in disease control. Dendritic cell (DC)- based immunotherapy is able to induce T cell responses against LAA and might therefore pose an interesting therapeutic option in CML, especially in the setting of minimal residual disease (MRD). GMP production of DC for clinical vaccination remains a time- and cost- intensive procedure and standardized DC generation is warranted. We asked whether maturation-induction with IFN-{gamma} and IFN-{alpha} has an influence on functional properties of DC derived from peripheral blood mononuclear cells (PBMC) in CML patients. Monocyte-derived DC from healthy donors and from patients with CML were analyzed after maturation-induction with our TNF-{alpha}-containing standard cytokine cocktail with or without addition of IFN-{alpha} and/or IFN-{gamma}. Our results confirm that the addition of IFN-{gamma} leads to enhanced IL-12 secretion in healthy donors. In contrast, in CML patients, IFN-{gamma} was not able to increase IL-12 secretion, possibly due to a higher degree of cell adherence and lower cell yield during the cell culture. Our data suggest, that- in contrast to healthy donors-, additional interferons are not beneficial for maturation induction during large-scale DC production in patients with CML

Glycaemic control in the perioperative period

The prevalence of type 2 diabetes mellitus and the potential for perioperative dysglycaemia (hyperglycaemia, hypoglycaemia, stress-induced hyperglycaemia, or glucose variability) continue to increase dramatically. The majority of investigations on perioperative glycaemic control focused on critically ill patients and concentrated on goals of therapy, level of intensity of insulin infusion, feeding regimes, concerns over hypoglycaemia, and promulgation of recent guidelines calling for less strict glucose control. Areas of perioperative glycaemic control that deserve further investigation include preoperative identification of patients with undiagnosed type 2 diabetes and other forms of dysglycaemia, determination of appropriate intraoperative glucose goals, and establishment of the impact and natural history of perioperative abnormalities in glucose homeostasis. In the heterogeneous adult perioperative population, it is unlikely that one standard of perioperative glycaemic control is appropriate for all patients. This review presents recent evidence and expert guidance to aid preoperative assessment, intraoperative management, and postoperative care of the dysglycaemic adult patien

Beam-Based Alignment of the NuMI Target Station Components at FNAL

The Neutrinos at the Main Injector (NuMI) facility is a conventional horn-focused neutrino beam which produces muon neutrinos from a beam of mesons directed into a long evacuated decay volume. The relative alignment of the primary proton beam, target, and focusing horns affects the neutrino energy spectrum delivered to experiments. This paper describes a check of the alignment of these components using the proton beam.Comment: higher resolution figures available on Fermilab Preprint Server (see SPIRES entry), accepted for publication in Nucl. Instr. and Meth.

Three-point correlations for quantum star graphs

We compute the three point correlation function for the eigenvalues of the Laplacian on quantum star graphs in the limit where the number of edges tends to infinity. This extends a work by Berkolaiko and Keating, where they get the 2-point correlation function and show that it follows neither Poisson, nor random matrix statistics. It makes use of the trace formula and combinatorial analysis.Comment: 10 pages, 2 figure

Gallbladder metastasis from renal cell carcinoma mimicking acute cholecystitis

Renal cell carcinoma constitutes about 3% of adult malignancies. It has a high metastatic potential associated with synchronous or metachronous metastatic disease. Further, it is known to metastasize mainly to the lung, bone, brain, liver, or adrenal glands. In very rare cases it can metastasize to the gallbladder mimicking acute cholecystitis on clinical exam. In this case we present a patient who developed a gallbladder metastasis five years after a renal cell carcinoma mimicking acute cholecystitis

Microencapsulation of clove essential oil with gelatin and alginate

Content: Essential oils are of commercial interest primarily because of their potential antimicrobial, antifungal and antioxidant properties and for being of natural origin, which generally represents lower risk to the environment and human health. Clove essential oil not only contains many kinds of biological active compositions but also has highly effective and comprehensive antibacterial functions. Remarkably, clove has strong antimicrobial activities against a wide range of pathogenic microorganisms. To prevent chemical changes the oil is microencapsulated. The aim of this study is to develop essential oil microcapsules with gelatin and alginate. Various solutions were prepared for the capsule wall material at different concentrations. The encapsulation efficiency (%) was accessed and the microcapsules were characterized by oil content (%), oil charge (%), morphology, functional groups present, thermogravimetric analysis and by Fourier transform - infrared spectral analysis. FT-IR spectra of the clove oil shows some special peaks at 1148,01 and 1033,33 cm-1. The spectra of the capsule showed peaks 1148.34 and 1033.29 cm -1, the same peaks present in clove oil, showing that the encapsulation did not alter the structure of the oil's main assets. In case of the gelatin and alginate microcapsules containing clove oil, most of the characteristic peaks of clove oil remained unchanged, indicating the successful incorporation of clove oil into the microcapsules and the chemical stability of the clove oil after encapsulation. In otherwords, there was no significant chemical interaction between the oil and the wall of the microcapsule. Take-Away: The clove oil was microencapsulated according the FTIR spectra