Influence of a macrolide antibiotic, roxithromycin, on mast cell growth and activation in vitro.

BACKGROUND: Long-term administration of macrolide antibiotics is recognized to be able to favorably modify the clinical condition of inflammatory diseases, such as diffuse panbronchiolitis and cystic fibrosis. However, the precise mechanisms by which macrolide antibiotics could improve clinical conditions of the patients are not well understood. AIM: The present study was designed to examine the influence of macrolide antibiotics on effector cell functions responsible for inflammation through the choice of roxithromycin (RXM) and mast cell. METHODS: Mast cells were induced by long-term culture of splenocytes from BALB/c mice. RXM was added to the cultures at seeding and then every 4-5 days, when the culture medium was replaced with a fresh one. The influence of RXM on mast cell growth was evaluated by counting the number of cells grown on the 16th day. We also examined the influence of RXM on mast cell activation by examining histamine release and inflammatory cytokine secretion. RESULTS AND CONCLUSION: RXM could not inhibit mast cell growth, even when splenocytes were exposed to 100 microg/ml of RXM throughout the entire culture periods. RXM also could not suppress histamine release from cultured mast cells in response to non-immunological and immunological stimulations. However, RXM could suppress inflammatory cytokine, interleukin-1beta, interleukin-6, granulocyte macrophage-colony stimulating factor and tumor necrosis factor-alpha, secretions induced by concanavalin A stimulation at a concentration of as little as 0.5 microg/ml. These results may suggest that RXM modulated the ability of mast cells to secrete inflammatory cytokines and results in improvement of clinical condition of chronic inflammatory diseases

Replica Method for Wide Correlators in Gaussian Orthogonal, Unitary And Symplectic Random Matrix Ensembles

We calculate connected correlators in Gaussian orthogonal, unitary and symplectic random matrix ensembles by the replica method in the 1/N-expansion. We obtain averaged one-point Green's functions up to the next-to-leading order O(1/N) and wide two-level correlators up to the first nontrivial order O(1/N^2) and wide three-level correlators up to the first nontrivial order $O(1/N^4)$ by carefully treating fluctuations in saddle-point evaluation.Comment: LaTeX 21 pages, a new result on wide three-level correlators adde

An asymptotic formula for marginal running coupling constants and universality of loglog corrections

Given a two-loop beta function for multiple marginal coupling constants, we derive an asymptotic formula for the running coupling constants driven to an infrared fixed point. It can play an important role in universal loglog corrections to physical quantities.Comment: 16 pages; typos fixed, one appendix removed for quick access to the main result; to be published in J. Phys.

A variability study of the Seyfert 2 galaxy NGC 6300 with XMM-Newton

We present the results of timing analysis of the XMM-Newton observation of the Seyfert 2 galaxy NGC 6300. The hard X-ray spectrum above 2 keV consists of a Compton-thin-absorbed power law, as is often seen in Seyfert 2 galaxies. We clearly detected rapid time variability on a time scale of about 1000 s from the light curve above 2 keV. The excess variance of the time variability (sigma2_RMS) is calculated to be ~0.12, and the periodogram of the light curve is well represented by a power law function with a slope of 1.75. In contrast with previous results from Seyfert 2 nuclei, these variability characteristics are consistent with those of Seyfert 1 galaxies. This consistency suggests that NGC 6300 has a similar black hole mass and accretion properties as Seyfert 1 galaxies. Using the relation between time variability and central black hole mass by Hayashida et al. (1998), the black hole mass of NGC 6300 is estimated to be ~2.8x10^5 Mo. Taking uncertainty of this method into account, the black hole mass is less than 10^7 Mo. Taking the bolometric luminosity of 3.3x10^43 erg/s into consideration, this yields an accretion rate of > 0.03 of the Eddington value, and comparable with estimates from Seyfert 1 galaxies using this method. The time variability analysis suggests that NGC 6300 actually has a Seyfert 1 nucleus obscured by a thick matter, and more generally provides a new pillar of support for the unified model of Seyfert galaxies based on obscuration.Comment: 11 pages, 6 figures, accepted for publication in Ap

NGC 7582: The Prototype Narrow-Line X-ray Galaxy

NGC 7582 is a candidate prototype of the Narrow Line X-ray Galaxies (NLXGs) found in deep X-ray surveys. An ASCA observation shows the hard (> 3 keV) X-ray continuum of NGC 7582 drops 40% in ~6 ks, implying an AGN, while the soft band (< 3 keV) does not drop in concert with the hard continuum, requiring a separate component. The X-ray spectrum of NGC 7582 also shows a clear 0.5-2 keV soft (kT = 0.8 (+0.9,-0.3) keV or Gamma = 2.4 +/- 0.6; L(X) = 6 x 10**40 ergs s**-1) low--energy component, in addition to a heavily absorbed [N(H) = (6 +/- 2)\times 10**22 cm**-2 ] and variable 2-10 keV power law [Gamma = 0.7 (+0.3,-0.4); L(X) = (1.7-2.3) x 10**42 ergs s**-1]. This is one of the flattest 2-10 keV slopes in any AGN observed with ASCA. (The ROSAT HRI image of NGC 7582 further suggests extent to the SE.) These observations make it clear that the hard X-ray emission of NGC 7582, the most "narrow-line" of the NLXGs, is associated with an AGN. The strong suggestion is that all NLXGs are obscured AGNs, as hypothesized to explain the X-ray background spectral paradox. The separate soft X-ray component makes NGC 7582 (and by extension other NLXGs) detectable as a ROSAT source.Comment: text: Latex2e 10 pages, including 1 table, and 2 postscript figures via psfi

Living donor liver transplantation from a donor previously treated with interferon for hepatitis C virus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Selecting a marginal donor in liver transplantation (LT) remains controversial but is necessary because of the small number of available donors.</p> <p>Case presentation</p> <p>A 46-year-old Japanese woman was a candidate to donate her liver to her brother, who had decompensated liver cirrhosis of unknown origin. Eight years before the donation, she had a mild liver dysfunction that was diagnosed as a hepatitis C virus (HCV) infection (serotype 2). She had received anti-viral therapy with interferon α-2b three times weekly for 24 weeks and had a sustained viral response (SVR). A biopsy of her liver before the donation showed normal findings without any active hepatitis, and her serum was negative for HCV-RNA. Only 67 patients have undergone LT from a cadaveric donor in Japan. The family in this case decided to have living donor LT. A careful selection for the liver graft donation was made; however, since she was the only candidate, we approved her as a living donor. She was discharged nine days after the liver donation. Her liver function recovered immediately. A computed tomography scan showed sufficient liver regeneration one year later. Her brother also had good liver function after LT and had no HCV infection 48 months after surgery and no <it>de novo </it>malignancy. Neither of the siblings has developed an HCV infection.</p> <p>Conclusions</p> <p>A patient with SVR status after interferon therapy might be considered a candidate for living donor LT but only if there are no other possibilities of LT for the recipient. A careful follow-up of the donor after donation is needed. The recipient also must have a very close follow-up because it is difficult to predict what might happen to the graft with post-transplant immunosuppression.</p

A two-domain elevator mechanism for sodium/proton antiport

Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1, 3, for which both electron microscopy and crystal structures are available4, 5, 6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1, 4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1, 8, 9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general

A gaming simulation approach to understanding blue ocean strategy development as a transition from traditional competitive strategy

Blue Ocean Strategy (BOS) has attracted a resurgence of interest following various market discontinuities, including digital disruption, the growth of the sharing economy and the development of ecosystems. BOS is a combination of value innovation and new markets, driving sustained higher performance through specific marketing activities, but it is difficult to conceive and implement. We outline five cases that use various transition paths to BOS through white spaces - with product extensions in the existing market. An important part of this transition are ‘blue ocean droplets’ which drive profitable growth through the transition and then onto a successful deployment of a blue ocean strategy. Blue ocean droplets drive profitable growth - simultaneously increasing volume sales, maintaining/increasing prices and maintaining/decreasing costs. We then use an inductive qualitative approach in a multi-team gaming simulation to examine drivers of firm performance. Higher than average performance is driven by repositioning in white spaces and execution of the three blue ocean droplets. Finally, we discuss implications for firms: execute a number of real options to follow one of several transition paths to a full BOS. This approach involves less downside risk than a full BOS approach, but can still be sustainably profitable, while also breaking the traditional value/cost trade-off

In situ proliferation and differentiation of macrophages in dental pulp

The presence of macrophages in dental pulp is well known. However, whether these macrophages proliferate and differentiate in the dental pulp in situ, or whether they constantly migrate from the blood stream into the dental pulp remains unknown. We have examined and compared the development of dental pulp macrophages in an organ culture system with in vivo tooth organs to clarify the developmental mechanism of these macrophages. The first mandibular molar tooth organs from ICR mice aged between 16 days of gestation (E16) to 5 days postnatally were used for in vivo experiments. Those from E16 were cultured for up to 14 days with or without 10% fetal bovine serum. Dental pulp tissues were analyzed with immunohistochemistry to detect the macrophages and with reverse transcription and the polymerase chain reaction (RT-PCR) for the detection of factors related to macrophage development. The growth curves for the in vivo and in vitro cultured cells revealed similar numbers of F4/80-positive macrophages in the dental pulp. RT-PCR analysis indicated the constant expression of myeloid colony-stimulating factor (M-CSF) in both in-vivo- and in-vitro-cultured dental pulp tissues. Anti-M-CSF antibodies significantly inhibited the increase in the number of macrophages in the dental pulp. These results suggest that (1) most of the dental pulp macrophages proliferate and differentiate in the dental pulp without a supply of precursor cells from the blood stream, (2) M-CSF might be a candidate molecule for dental pulp macrophage development, and (3) serum factors might not directly affect the development of macrophages