Discovery of Year-scale Time Variability from Thermal X-Ray Emission in Tycho’s Supernova Remnant

ティコの超新星残骸で増光する構造を発見 --加熱過程をリアルタイムで捉える--. 京都大学プレスリリース. 2022-11-29.Mechanisms of particle heating are crucial to understanding the shock physics in supernova remnants (SNRs). However, there has been little information on time variabilities of thermalized particles so far. Here, we present a discovery of a gradually brightening thermal X-ray emission found in the Chandra data of Tycho's SNR obtained during 2000–2015. The emission exhibits a knot-like feature (Knot1) with a diameter of ≃0.04 pc located in the northwestern limb, where we also find localized Hα filaments in an optical image taken with the Hubble Space Telescope in 2008. The model with the solar abundance reproduces the spectra of Knot1, suggesting that Knot1 originates from the interstellar medium; this is the first detection of thermal X-ray emission from swept-up gas found in Tycho's SNR. Our spectral analysis indicates that the electron temperature of Knot1 has increased from ∼0.30 to ∼0.69 keV within the period between 2000 and 2015. These results lead us to ascribe the time-variable emission to a small dense clump recently heated by the forward shock at the location of Knot1. The electron-to-proton temperature ratio immediately downstream of the shock (β₀ ≡ Te/Tp) is constrained to be me/mp ≤ β₀ ≤ 0.15 to reproduce the data, indicating the collisionless electron heating with efficiency is consistent with previous Hα observations of Tycho and other SNRs with high shock velocities

Early and Definitive Diagnosis of Toxic Shock Syndrome by Detection of Marked Expansion of T-Cell-Receptor Vβ2-Positive T Cells

We describe two cases of early toxic shock syndrome, caused by the superantigen produced from methicillin-resistant Staphylococcus aureus and diagnosed on the basis of an expansion of T-cell-receptor Vβ2-positive T cells. One case-patient showed atypical symptoms. Our results indicate that diagnostic systems incorporating laboratory techniques are essential for rapid, definitive diagnosis of toxic shock syndrome

A case of isolated ACTH deficiency that required 6 months for the diagnosis from onset

A 53-year-old man noticed anorexia, nausea, and arthralgia of the upper limbs in April, 201X. Since these symptoms persisted, he visited general hospital and clinic and was examined for blood chemistry, ECG, echocardiography and so on. However, he did not get a definitive diagnosis and was followed up with drip infusion of saline. The symptoms did not subside and fatigue and syncope with hypotension developed. Furthermore, he also suffered weight loss of 10 kg in few months and was referred to our hospital for more detailed examinations in October, 201X. Upon the initial examination, all his symptoms matched those of adrenal insufficiency and notable decreases of both plasma ACTH and serum cortisol level were observed. Prompt glucocorticoid supplementation improved his symptoms and the abnormal laboratory data immediately. He was diagnosed adrenal insufficiency due to isolated ACTH deficiency from the results of CRH loading test and insulin tolerance test. Since most of the symptoms and laboratory findings are non-specific, diagnosis of adrenal insufficiency is often delayed. However, adrenal insufficiency could worsen when the patient is under stress (e.g. infection) and often be life-threatening. Glucocorticoid replacement therapy should be initiated as soon as the diagnosis is confirmed. Furthermore, educating patients and his families plays a very important role in the management of chronic adrenal insufficiency, in particular to the prevention of adrenal crisis

Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer

<p>Abstract</p> <p>Background</p> <p>T-cell based immunotherapy for lung cancer (LC) could be a promising and novel therapeutic approach. Six-transmembrane epithelial antigen of the prostate (STEAP) and the polycomb group protein enhancer of zeste homolog 2 (EZH2) are highly expressed in LC and since the expression of molecules in normal tissue is significantly lower as compared to tumor cells, these proteins are considered as potential tumor-associated antigens (TAAs) for developing T-cell based immunotherapy.</p> <p>Methods</p> <p>We assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines.</p> <p>Results</p> <p>Out of several predicted epitopes, two synthetic peptides, STEAP_281-296and EZH2_95-109, were effective in inducing CD4 T-cell responses that were restricted by HLA-DR1, DR15, or DR53 molecules, indicating that the peptides function as promiscuous T-cell epitopes. Moreover, STEAP_281-296and EZH2_95-109-reactive T-cells could directly recognize STEAP or EZH2 expressing LC cells in an HLA-DR restricted manner. In addition, some STEAP-reactive T-cells responded to STEAP+ tumor cell lysates presented by autologous dendric cells. Most significantly, both of these peptides were capable of stimulating <it>in vitro </it>T-cell responses in patients with LC.</p> <p>Conclusions</p> <p>Peptides STEAP_281-296and EZH2_95-109function as strong CD4 T-cell epitopes that can elicit effective anti-tumor T-cell responses against STEAP or EZH2 expressing LC. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of LC.</p

Utility of Shear Wave Elastography for Diagnosing Chronic Autoimmune Thyroiditis

The aims of this study were to evaluate the utility of shear wave elastography (SWE) using acoustic radiation force impulse (ARFI) for diagnosing chronic autoimmune thyroiditis (CAT) and to verify the effect of fibrotic thyroid tissue on shear wave velocity (SWV). The subjects were 229 patients with 253 normal thyroid lobes (controls) and 150 CAT lobes. The SWV for CAT (2.47 ± 0.57 m/s) was significantly higher than that for controls (1.59 ± 0.41 m/s) (P<0.001). The area under the receiver operating characteristics (ROC) curve for CAT was 0.899, and the SWV cut-off value was 1.96 m/s. The sensitivity, specificity, and diagnostic accuracy were 87.4%, 78.7%, and 85.1%, respectively. Levels of anti-thyroperoxidase antibodies and thyroid isthmus thickness were correlated with tissue stiffness in CAT. However, there was no correlation between levels of anti-thyroglobulin antibodies and tissue stiffness. Quantitative SWE is useful for diagnosing CAT, and it is possible that SWE can be used to evaluate the degree of fibrosis in patients with CAT

The mechanism of Tyk2 deficiency-induced immunosuppression in mice involves robust IL-10 production in macrophages

Macrophages are highly plastic in their pro-inflammatory/anti-inflammatory roles. Type I and II interferons (IFNs) are known to modulate macrophage activation. Tyrosine kinase 2 (Tyk2) has an intimate relationship with type I and II IFN signaling. Animal studies have shown that Tyk2 knock-out (KO) in mice is associated with reduced inflammatory responses in various mouse models of diseases. To investigate the role of Tyk2 in inflammation in more detail, we intraperitoneally injected heat-killed Propionibacterium acnes (P. acnes) to Tyk2 KO mice. P. acnes-induced acute peritoneal inflammation, assessed by neutrophil infiltration, was reduced in Tyk2 KO mice. The reduction was accompanied with diminished productions of inflammatory cytokines and an enhanced production of anti-inflammatory IL-10. Unexpectedly, pre-treatment of wild-type mice with the neutralizing antibodies for IFNs did not affect P. acnes-induced neutrophil infiltration. A neutralizing antibody for the IL-10 receptor in Tyk2 KO mice restored P. acnes-induced peritoneal inflammation. Enhanced production of IL-10 from Tyk2 KO peritoneal cells was suppressed by either the cyclooxygenase inhibitor diclofenac or protein kinase A inhibitor H-89. The level of prostaglandin E-2 (PGE(2)) in the steady-state peritoneal cavity in Tyk2 KO mice was higher than that in wild-type mice. Tyk2 KO macrophages showed an enhanced CREB phosphorylation induced by P. acnes plus PGE(2). Taken together, these results showed that Tyk2 deficiency potentiates the PGE(2)-protein kinase A-IL-10 pathway in macrophages, and thereby contributes to potentiation of the immunosuppressive phenotype