Time Variability of Nonthermal X-ray Stripes in Tycho's Supernova Remnant with Chandra

Analyzing Chandra data of Tycho's supernova remnant (SNR) taken in 2000, 2003, 2007, 2009, and 2015, we search for time variable features of synchrotron X-rays in the southwestern part of the SNR, where stripe structures of hard X-ray emission were previous found. By comparing X-ray images obtained at each epoch, we discover a knot-like structure in the northernmost part of the stripe region became brighter particularly in 2015. We also find a bright filamentary structure gradually became fainter and narrower as it moved outward. Our spectral analysis reveal that not only the nonthermal X-ray flux but also the photon indices of the knot-like structure change from year to year. During the period from 2000 to 2015, the small knot shows brightening of $\sim 70\%$ and hardening of $\Delta \Gamma \sim 0.45$. The time variability can be explained if the magnetic field is amplified to $\sim 100~\mathrm{\mu G}$ and/or if magnetic turbulence significantly changes with time.Comment: 8 pages, 3 figures, 2 tables, accepted for publication in Ap

Very-Low-Dose Pegylated Interferon a2a Plus Ribavirin Therapy for Advanced Liver Cirrhosis Type C: A Possible Therapeutic Alternative without Splenic Intervention

Despite the recent progress in interferon (IFN) therapies for chronic hepatitis C, liver cirrhosis remains refractory. One of the major obstacles to successful IFN therapy is low platelet count. Currently, splenic interventions, such as partial splenic embolization (PSE) or surgical splenectomy, have been applied effectively and make standard IFN therapy possible. However, there may be a group of patients with low platelet counts who can be treated without splenic intervention. We here report two patients with advanced type C liver cirrhosis who were successfully treated using very-low-dose pegylated interferon a2a plus ribavirin. One patient had a very low platelet count (2.5 × 104/μl) due to splenomegaly before treatment. However, pretreatment serum HCV titers were low in both patients and early viral responses were obtained in both. Because PSE or splenectomy may still have some safety concerns, this attenuated IFN treatment protocol can be an alternative therapeutic option for patients with advanced type C liver disease, but good virological factors for sustained virological response

cis interaction of CD153 with TCR/CD3 is crucial for the pathogenic activation of senescence-associated T cells

老化T細胞が自己免疫病や慢性炎症疾患を引き起こすメカニズムを解明 --老化関連疾患克服への新しいアプローチ--. 京都大学プレスリリース. 2022-09-22.With age, senescence-associated (SA) CD4+ T cells that are refractory to T cell receptor (TCR) stimulation are increased along with spontaneous germinal center (Spt-GC) development prone to autoantibody production. We demonstrate that CD153 and its receptor CD30 are expressed in SA-T and Spt-GC B cells, respectively, and deficiency of either CD153 or CD30 results in the compromised increase of both cell types. CD153 engagement on SA-T cells upon TCR stimulation causes association of CD153 with the TCR/CD3 complex and restores TCR signaling, whereas CD30 engagement on GC B cells induces their expansion. Administration of an anti-CD153 antibody blocking the interaction with CD30 suppresses the increase in both SA-T and Spt-GC B cells with age and ameliorates lupus in lupus-prone mice. These results suggest that the molecular interaction of CD153 and CD30 plays a central role in the reciprocal activation of SA-T and Spt-GC B cells, leading to immunosenescent phenotypes and autoimmunity

Successful Treatment in a Case of Massive Hepatocellular Carcinoma with Paraneoplastic Syndrome

Paraneoplastic syndromes of hepatocellular carcinoma (HCC) are not uncommon. However, the prognosis is poor and follow-up and improvement of paraneoplastic syndromes with treatment have been reported rarely. We report a successful case in an aged man of a massive HCC with paraneoplastic syndrome, treated by combined intraarterial chemotherapy and hepatic resection. Paraneoplastic syndrome (erythrocytosis and hyperlipidemia) was monitored throughout the treatment and erythropoietin (EPO) mRNA also was analyzed in the resected liver. The hemoglobin level and serum levels of EPO and total cholesterol (T-cho) decreased dramatically with treatment, along with a decrease in serum levels of α-fetoprotein and protein induced by vitamin vitamin K absence II (PIVKA-II). Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) revealed that the residual cancer expressed EPO RNA but the nontumor tissue did not. This was a rare case of paraneoplastic syndrome of HCC that was treated successfully. This case indicates that paraneoplastic syndrome reflected tumor progression and that serum levels of both EPO and T-cho might be used as tumor markers

DNA Damage Sensor γ

Background. Phosphorylated histone H2AX (γ-H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ-H2AX in hepatocellular carcinoma (HCC), we measured the level of γ-H2AX in HCC, dysplastic nodule, and nontumorous liver diseases. Methods. The level of γ-H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules. Appropriate cases were also examined by fluorescence analysis and western blotting. Results. All cases with chronic liver disease showed increased levels of γ-H2AX expression. In 40 (69.9%) of 58 cases with HCC, the labeling index (LI) of γ-H2AX was above 50% and was inversely correlated with the histological grade. Mean γ-H2AX LI was the highest in dysplastic nodule (74.1±22.1%), which was significantly higher than HCC (P<0.005). Moreover, γ-H2AX was significantly increased in nontumorous tissues of HCC as compared with liver cirrhosis without HCC (62.5±24.7%, from 5.1 to 96.0%, P<0.005). Conclusions. γ-H2AX was increased in the preneoplastic lesions of HCC and might be a useful biomarker for predicting the risk of HCC

Free surface flows emerging from beneath a semi-infinite plate with constant vorticity

The free surface flow past a semi-infinite horizontal plate in a finite-depth fluid is considered. It is assumed that the fluid is incompressible and inviscid and that the flow approaches a uniform shear flow downstream. Exact relations are derived using conservation of mass and momentum for the case where the downstream free surface is flat. The complete nonlinear problem is solved numerically using a boundary integral method and these waveless solutions are shown to exist only when the height of the plate above the bottom is greater than the height of the uniform shear flow. Interesting results are found for various values of the constant vorticity. Solutions with downstream surface waves are also considered, and nonlinear results of this type are compared with linear results found previously. These solutions can be used to model the flow near the stern of a (two-dimensional) ship

Molecular mechanism underlying the functional loss of cyclindependent kinase inhibitors p16 and p27 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common human cancers, and its incidence is still increasing in many countries. The prognosis of HCC patients remains poor, and identification of useful molecular prognostic markers is required. Many recent studies have shown that functional alterations of cell-cycle regulators can be observed in HCC. Among the various types of cell-cycle regulators, p16 and p27 are frequently inactivated in HCC and are considered to be potent tumor suppressors. p16, a G1-specific cell-cycle inhibitor that prevents the association of cyclindependent kinase (CDK) 4 and CDK6 with cyclin D1, is frequently inactivated in HCC via CpG methylation of its promoter region. p16 may be involved in the early steps of hepatocarcinogenesis, since p16 gene methylation has been detected in subsets of pre-neoplastic liver cirrhosis patients. p27, a negative regulator of the G1-S phase transition through inhibition of the kinase activities of Cdk2/cyclin A and Cdk2/cyclin E complexes, is now considered to be an adverse prognostic factor in HCC. In some cases of HCC with increased cell proliferation, p27 is overexpressed but inactivated by sequestration into cyclin D1-CDK4-containing complexes. Since loss of p16 is closely related to functional inactivation of p27 in HCC, investigating both p16 and p27 may be useful for precise prognostic predictions in individuals with HCC