Streptococcal infection and autoimmune diseases

Excessive activation of immune cells by environmental factors, such as infection or individual genetic risk, causes various autoimmune diseases. Streptococcus species are gram-positive bacteria that colonize the nasopharynx, respiratory tract, gastrointestinal tract, genitourinary tract, and skin. Group A Streptococcus (GAS) species cause various symptoms, ranging from mild infections, such as tonsillitis and pharyngitis, to serious infections, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The contribution of GAS infections to several autoimmune diseases, including acute rheumatic fever, vasculitis, and neuropsychiatric disorders, has been studied. In this review, we focus on the association between streptococcal infections and autoimmune diseases, and discuss current research on the mechanisms underlying the initiation and progression of autoimmune diseases

Innate immune responses in Behçet disease and relapsing polychondritis

Behçet disease (BD) and relapsing polychondritis (RP) are chronic multisystem disorders characterized by recurrent flare-ups of tissue inflammation. Major clinical manifestations of BD are oral aphthae, genital aphthous ulcers, skin lesions, arthritis, and uveitis. Patients with BD may develop rare but serious neural, intestinal, and vascular complications, with high relapse rates. Meanwhile, RP is characterized by the inflammation of the cartilaginous tissues of the ears, nose, peripheral joints, and tracheobronchial tree. Additionally, it affects the proteoglycan-rich structures in the eyes, inner ear, heart, blood vessels, and kidneys. The mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is a common characteristic of BD and RP. The immunopathology of these two diseases may be closely related. It is established that the genetic predisposition to BD is related to the human leukocyte antigen (HLA)-B51 gene. Skin histopathology demonstrates the overactivation of innate immunity, such as neutrophilic dermatitis/panniculitis, in patients with BD. Monocytes and neutrophils frequently infiltrate cartilaginous tissues of patients with RP. Somatic mutations in UBA1, which encodes a ubiquitylation-related enzyme, cause vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) with severe systemic inflammation and activation of myeloid cells. VEXAS prompts auricular and/or nasal chondritis, with neutrophilic infiltration around the cartilage in 52–60% of patients. Thus, innate immune cells may play an important role in the initiation of inflammatory processes underlying both diseases. This review summarizes the recent advances in our understanding of the innate cell-mediated immunopathology of BD and RP, with a focus on the common and distinct features of these mechanisms

A Shock-Induced Pair of Superbubbles in the High-Redshift Powerful Radio Galaxy MRC 0406-244

We present new optical spectroscopy of the high-redshift powerful radio galaxy MRC 0406$-$244 at redshift of 2.429. We find that the two extensions toward NW and SE probed in the rest-frame ultraviolet image are heated mainly by the nonthermal continuum of the active galactic nucleus. However, each extension shows a shell-like morphology, suggesting that they are a pair of superbubbles induced by the superwind activity rather than by the interaction between the radio jet and the ambient gas clouds. If this is the case, the intense starburst responsible for the formation of superbubbles could occur $\sim 1 \times 10^9$ yr ago. On the other hand, the age of the radio jets may be of the order of $\sim 10^6$ yr, being much shorter than the starburst age. Therefore, the two events, i.e., the starburst and the radio-jet activities, are independent phenomena. However, their directions of the expanding motions could be governed by the rotational motion of the gaseous component in the host galaxy. This idea appears to explain the alignment effect of MRC 0406$-$244.Comment: 4 pages (emulateapj.sty), Fig. 1 (jpeg) + Fig.2 (eps). Accepted for publications in ApJ (Letters

The End of the Reionization Epoch Probed by Ly-alpha Emitters at z=6.5 in the Subaru Deep Field

We report an extensive search for Lyman-alpha emitters (LAEs) at z=6.5 in the Subaru Deep Field. Subsequent spectroscopy with Subaru and Keck identified eight more LAEs, giving a total of 17 spectroscopically confirmed LAEs at z=6.5. Based on this spectroscopic sample of 17, complemented by a photometric sample of 58 LAEs, we have derived a more accurate Lyman-alpha luminosity function of LAEs at z=6.5, which reveals an apparent deficit at the bright end of ~0.75 mag fainter L*, compared with that observed at z=5.7. The difference in the LAE luminosity functions between z=5.7 and 6.5 is significant at the 3-sigma level, which is reduced to 2-sigma when cosmic variance is taken into account. This result may imply that the reionization of the universe has not been completed at z=6.5. We found that the spatial distribution of LAEs at z=6.5 was homogeneous over the field. We discuss the implications of these results for the reionization of the universe.Comment: To appear in APJ vol.648. Only minor corrections have been made. Black&White version is available at http://zone.mtk.nao.ac.jp/~kashik/sdf/z6p5lae/paper/sdf_z6p5lae_bw.pd

Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety

<p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) stimulates hepatocyte proliferation, and also acts as an anti-apoptotic factor. Therefore, HGF is a potential therapeutic agent for treatment of fatal liver diseases. We performed a translational medicine protocol with recombinant human HGF (rh-HGF), including a phase I/II study of patients with fulminant hepatitis (FH) or late-onset hepatic failure (LOHF), in order to examine the safety, pharmacokinetics, and clinical efficacy of this molecule.</p> <p>Methods</p> <p>Potential adverse effects identified through preclinical safety tests with rh-HGF include a decrease in blood pressure (BP) and an increase in urinary excretion of albumin. Therefore, we further investigated the effect of rh-HGF on circulatory status and renal toxicity in preclinical animal studies. In a clinical trial, 20 patients with FH or LOHF were evaluated for participation in this clinical trial, and four patients were enrolled. Subjects received rh-HGF (0.6 mg/m²/day) intravenously for 12 to 14 days.</p> <p>Results</p> <p>We established an infusion method to avoid rapid BP reduction in miniature swine, and confirmed reversibility of renal toxicity in rats. Although administration of rh-HGF moderately decreased BP in the participating subjects, this BP reduction did not require cessation of rh-HGF or any vasopressor therapy; BP returned to resting levels after the completion of rh-HGF infusion. Repeated doses of rh-HGF did not induce renal toxicity, and severe adverse events were not observed. Two patients survived, however, there was no evidence that rh-HGF was effective for the treatment of FH or LOHF.</p> <p>Conclusions</p> <p>Intravenous rh-HGF at a dose of 0.6 mg/m²was well tolerated in patients with FH or LOHF; therefore, it is desirable to conduct further investigations to determine the efficacy of rh-HGF at an increased dose.</p

Clustering of Lyman Break Galaxies at z=4 and 5 in The Subaru Deep Field: Luminosity Dependence of The Correlation Function Slope

We explored the clustering properties of Lyman Break Galaxies (LBGs) at z=4 and 5 with an angular two-point correlation function on the basis of the very deep and wide Subaru Deep Field data. We found an apparent dependence of the correlation function slope on UV luminosity for LBGs at both z=4 and 5. More luminous LBGs have a steeper correlation function. To compare these observational results, we constructed numerical mock LBG catalogs based on a semianalytic model of hierarchical clustering combined with high-resolution N-body simulation, carefully mimicking the observational selection effects. The luminosity functions for LBGs predicted by this mock catalog were found to be almost consistent with the observation. Moreover, the overall correlation functions of LBGs were reproduced reasonably well. The observed dependence of the clustering on UV luminosity was not reproduced by the model, unless subsamples of distinct halo mass were considered. That is, LBGs belonging to more massive dark haloes had steeper and larger-amplitude correlation functions. With this model, we found that LBG multiplicity in massive dark halos amplifies the clustering strength at small scales, which steepens the slope of the correlation function. The hierarchical clustering model could therefore be reconciled with the observed luminosity-dependence of the angular correlation function, if there is a tight correlation between UV luminosity and halo mass. Our finding that the slope of the correlation function depends on luminosity could be an indication that massive dark halos hosted multiple bright LBGs (abridged).Comment: 16 pages, 17 figures, Accepted for publication in ApJ, Full resolution version is available at http://zone.mtk.nao.ac.jp/~kashik/sdf/acf/sdf_lbgacf.pd

Exploring deep microbial life in coal-bearing sediment down to ~2.5 km below the ocean floor

Peer reviewedPostprin

Propionate-producing bacteria in the intestine may associate with skewed responses of IL10-producing regulatory T cells in patients with relapsing polychondritis.

Relapsing polychondritis (RP) is an inflammatory disease of unknown causes, characterized by recurrent inflammation in cartilaginous tissues of the whole body. Recently, researchers have reported that, in mouse experiments, altered gut microbe-dependent T cell differentiation occurred in gut associated lymphoid tissues. Here, we investigated whether gut microbe alteration existed, and if so, the alteration affected peripheral T cell differentiation in patients with RP. In an analysis of gut microbiota, we found increased annotated species numbers in RP patients compared with normal individuals. In the RP gut microbiota, we observed several predominant species, namely Veillonella parvula, Bacteroides eggerthii, Bacteroides fragilis, Ruminococcus bromii, and Eubacterium dolichum, all species of which were reported to associate with propionate production in human intestine. Propionate is a short-chain fatty acid and is suggested to associate with interleukin (IL)10-producing regulatory T (Treg) cell differentiation in gut associated lymphoid tissues. IL10 gene expressions were moderately higher in freshly isolated peripheral blood mononuclear cells (PBMC) of RP patients than those of normal individuals. Six hours after the initiation of the cell culture, regardless of the presence and absence of mitogen stimulation, IL10 gene expressions were significantly lower in RP patients than those in normal individuals. It is well known that PBMC of patients with autoimmune and inflammatory diseases show hyporesponsiveness to mitogen stimulation. We suggest that, in RP patients, continuous stimulation of intestinal T cells by excessive propionate leads to the spontaneous IL10 production and a subsequent refractory period of T cells in patients with RP. The hyporesponsiveness of Treg cells upon activation may associate with inflammatory cytokine production of PBMC and subsequently relate to chondritis in RP patients

Ly alpha emitters at z=5.7 in the Subaru deep field

We present the properties of Ly Alpha emitters (LAEs) at z = 5.7 in the Subaru Deep Field. A photometric sample of 89 LAE candidates is constructed from narrow-band (NB816) data down to NB816 = 26.0 (AB) in a continuous 725 arcmin^2 area. Spectra of 39 objects satisfying the photometric selection criteria for LAEs were obtained with Subaru and Keck II Telescopes, among which 28 were confirmed LAEs, one was a nearby galaxy, and eight were unclassified. We also obtained spectra of another 24 NB816-excess objects in the field, identifying six additional LAEs. We find that the Ly Alpha luminosity function derived from the photometric sample is reproduced well by a Schechter function with L* = (7.9+3.0-2.2) x 10^42 erg/s and phi* = (6.3+3.0-2.0) x 10^-4 Mpc^-3 for alpha = -1.5 (fixed) over the whole luminosity range of L ~= 3x10^42 - 3x10^43 erg/s. We then measure rest-frame Ly Alpha equivalent widths (EWs) for the confirmed LAEs, to find that the median among the 28 objects satisfying the photometric selection criteria is W_0^i = 233 A. We infer that 30% - 40% of LAEs at z=5.7 exceed W_0^i = 240 A. These large-EW objects probably cannot be accounted for by ordinary star-forming populations with a Salpeter IMF. We also find that LAEs with fainter far-UV luminosities have larger EWs. Finally, we derive the far-UV luminosity function of LAEs down to M_UV ~= -19.6 using the photometric sample, and compare it with that of Lyman-break galaxies (LBGs). We find that as high as about 80% of LBGs at z ~ 6 have W_0^i &gt;= 100 A, in sharp contrast to lower-z counterparts