Recent advances in our understanding of the immune response are allowing for the logical design of new approaches to cancer immunization. Bacterial DNA is capable of inducing activation of B cells, NK cells, and monocytes (1-5). In addition, bacterial DNA can induce production in vitro and in vivo of a variety of proinflammatory cytokines (6-8). In contrast, vertebrate DNA does not induce lymphocyte activation. Bacterial DNA contains a much higher frequency of unmethylated CpG dinucleotides than does vertebrate DNA due to (i) CpG suppression (the under representation of CpG in vertebrate genomes) and (ii) methylation of 80% of the CpG in vertebrates. It is possible that lymphocyte activation by the CpG motif in bacterial DNA represents an immune defense mechanism that can distinguish bacterial from host DNA (1). Select synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) have immunologic effects similar to those seen with bacterial DNA. CpG ODN can stimulate monocytes, macrophages, and dendritic cells that then produce several cytokines, including the TH1 cytokine interleukin 12. This effect synergizes with CpG ODN to induce NK cell production of interferon ␥ (6). Both human and murine leukocytes respond to this novel pathway of immune activation, although individual CpG ODN differ somewhat in their ability to activate various immune cell populations and induce cytokine production in human and murine systems.The molecular mechanisms responsible for CpG ODNinduced immune cell activation are still under investigation. We have recently reported that CpG ODN trigger the production of reactive oxygen species that activate NF-B (9). This activation, in turn, leads to cellular activation. Irrespective of the mechanism involved, it is clear that select CpG ODN can have powerful immunologic effects and might be useful therapeutic agents in a number of circumstances, including cancer immunotherapy. For example, we have demonstrated that CpG ODN can enhance antibody-dependent cellular cytotoxicity and improve the in vivo efficacy of monoclonal antibody therapy in a syngeneic murine lymphoma model (10).CpG ODN can induce activation of antigen-presenting cells and enhance production of cytokines known to participate in the development of an active immune response. They also enhance B cell activation, particularly when the B cell receptor is cross-linked (1). These effects are likely to promote antigenspecific responses. Indeed, Branda et al. (11) demonstrated that an anti-sense ODN, which in retrospect is noted to contain the CpG motif, enhances antibody response to antigen. We therefore used a well-established animal model to assess whether CpG ODN can function as an immune adjuvant in antitumor immunization.

We have established a simple three-variable Formosa score for KD patients to identify early those at risk of IVIG unresponsiveness for timely aggressive immunomodulation initially.

Background: Kawasaki disease (KD) is an acute systemic vasculitis that occurs in children and may lead to cardiovascular morbidity and mortality. Progressive coronary dilatation for at least 2 months is associated with worse late coronary outcomes in patients with KD having medium or giant aneurysms. However, the risk factors and occurrence of progressive coronary dilatation in patients with KD but without medium or giant aneurysms have been insufficiently explored. Methods: We retrospectively enrolled 169 patients with KD from a tertiary medical center in Taiwan during [2009][2010][2011][2012][2013]. Medical records of all patients were reviewed. Echocardiography was performed during the acute KD phase and at 3-4 weeks, 6-8 weeks, 6 months, and 12 months after KD onset. Progressive coronary dilatation was defined as the progressive enlargement of coronary arteries on three consecutive echocardiograms. Logistic regression analysis was conducted to evaluate the potential risk factors for coronary aneurysms and progressive coronary dilatation. Results: Of a total of 169 patients with KD, 31 (18.3%) had maximal coronary Z-scores of ≥ + 2.5 during the acute KD phase, 16 (9.5%; male/female: 9/7) had coronary aneurysms at 1 month after KD onset, and 5 (3.0%) satisfied the definition of progressive coronary dilatation. Multivariate logistic regression analysis revealed that an initial maximal coronary Z-score of ≥ + 2.5 [odds ratio (OR): 5.24, 95% confidence interval (CI): 1.31-21.3, P = 0.020] and hypoalbuminemia (OR: 4.83, 95% CI: 1.11-20.9, P = 0.035) were independent risk factors for coronary aneurysms and were significantly associated with progressive coronary dilatation. However, the association between intravenous immunoglobulin unresponsiveness and the development of coronary aneurysms at 1 month after KD onset didn't reach the level of significance (P = 0.058). Conclusions: In the present study, 3% (5/169) of patients with KD had progressive coronary dilatation, which was associated with persistent coronary aneurysms at 1 year after KD onset. Initial coronary dilatation and hypoalbuminemia were independently associated with the occurrence of progressive coronary dilatation. Therefore, such patients may require intensive cardiac monitoring and adjuvant therapies apart from immunoglobulin therapies.

The dust properties in high-redshift galaxies provide clues to the origin of dust in the Universe. Although dust has been detected in galaxies at redshift z > 7, it is difficult to constrain the dominant dust sources only from the total dust amount. Thus, we calculate the evolution of grain size distribution, expecting that different dust sources predict different grain size distributions. Using the star formation time-scale and the total baryonic mass constrained by the data in the literature, we calculate the evolution of grain size distribution. To explain the total dust masses in ALMA-detected z > 7 galaxies, the following two solutions are possible: (i) high dust condensation efficiency in stellar ejecta, and (ii) efficient accretion (dust growth by accreting the gas-phase metals in the interstellar medium). We find that these two scenarios predict significantly different grain size distributions: in (i), the dust is dominated by large grains (a 0.1 µm, where a is the grain radius), while in (ii), the small-grain (a 0.01 µm) abundance is significantly enhanced by accretion. Accordingly, extinction curves are expected to be much steeper in (ii) than in (i). Thus, we conclude that extinction curves provide a viable way to distinguish the dominant dust sources in the early phase of galaxy evolution.

Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can activate various immune cell subsets and induce production of a number of cytokines. Prior studies have demonstrated that both CpG ODN and granulocyte-macrophage colony-stimulating factor (GM-CSF) can serve as potent vaccine adjuvants. We used the 38C13 murine lymphoma system to evaluate the immune response to a combination of these two adjuvants. Immunization using antigen, CpG ODN, and soluble GM-CSF enhanced production of antigen-specific antibody and shifted production towards the IgG2a isotype, suggesting an enhanced TH1 response. This effect was most pronounced after repeat immunizations with CpG ODN and antigen/GM-CSF fusion protein. A single immunization with CpG ODN and antigen/GM-CSF fusion protein 3 days before tumor inoculation prevented tumor growth. CpG ODN enhanced the production of interleukin-12 by bone marrow-derived dendritic cells and increased expression of major histocompatibility complex class I and class II molecules, particularly when cells were pulsed with antigen/GM-CSF fusion protein. We conclude that the use of CpG ODN in combination with strategies involving GM-CSF enhances the immune response to antigen and shifts the response towards a TH1 response and that this approach deserves further evaluation in tumor immunization approaches and other conditions in which an antigen-specific TH1 response is desirable.