Nivolumab-induced IgA nephropathy in a patient with advanced gastric cancer A case report

Introduction: Immune checkpoint inhibitors including nivolumab, an antibody against programmed death-1, have been increasingly introduced in various cancer treatment regimens, and are reported to be associated with immune-related adverse events. Nivolumab-induced renal injury is generally caused by acute interstitial nephritis and is managed by drug discontinuation and steroid therapy. Although this agent can infrequently induce glomerulonephritis, the pathogenesis and therapeutic strategy remain undetermined. Patient concerns: A 78-year-old man was diagnosed with advanced gastric cancer with portal thrombosis. First- and second-line chemotherapies were ineffective; thus, nivolumab monotherapy was initiated. Although it effectively prevented tumor growth, proteinuria and microhematuria appeared 2 months later. Despite drug discontinuation, serum creatinine progressively increased from 0.72 to 1.45 mg/dL. Renal biopsy revealed mesangial IgA and C3 deposition in immunofluorescence analysis and mesangial proliferation with crescent formation in light microscopy. Diagnosis: The patient was diagnosed with IgA nephropathy. Based on the temporal relationship between the nivolumab therapy and abnormal urinalysis, IgA nephropathy was considered to have been induced by nivolumab. Interventions: A moderate dose (0.6 mg/kg/day) of prednisolone was orally administrated, with tapering biweekly. Outcomes: Steroid therapy stabilized his serum creatinine levels and markedly reduced proteinuria. However, bacterial pneumonia substantially impaired his performance status; thus, nivolumab could not be restarted despite tumor regrowth. Lessons: IgA nephropathy should be recognized as an uncommon renal adverse event during nivolumab therapy. After drug discontinuation, nivolumab-induced IgA nephropathy is likely to respond to moderate doses of steroid therapy with early tapering. However, more evidence is needed to determine whether nivolumab can be safely restarted during or after steroid therapy

AKARI/FIS Mapping of the ISM-Wind Bow Shock around Alpha Ori

We present 10' x 50' scan maps around an M supergiant Alpha Ori at 65, 90, 140 and 160 microns obtained with the AKARI Infrared Astronomy Satellite. Higher spatial resolution data with the exact analytic solution permit us to fit the de-projected shape of the stellar wind bow shock around Alpha Ori to have the stand-off distance of 4.8', position angle of 55 degrees and inclination angle of 56 degrees. The shape of the bow shock suggests that the peculiar velocity of Alpha Ori with respect to the local medium is v_* = 40 (n_H)^(-1/2), where n_H is the hydrogen nucleus density at Alpha Ori. We find that the local medium is of n_H = 1.5 to 1.9 cm^(-3) and the velocity of the local flow is at 11 km s^(-1) by using the most recent astrometric solutions for Alpha Ori under the assumption that the local medium is moving away from the Orion OB 1 association. AKARI images may also reveal a vortex ring due to instabilities on the surface of the bow shock as demonstrated by numerical models. This research exemplifies the potential of AKARI All-Sky data as well as follow-up observations with Herschel Space Telescope and Stratospheric Observatory for Infrared Astronomy for this avenue of research in revealing the nature of interaction between the stellar wind and interstellar medium.Comment: 8 pages, 2 figures, to be published in PASJ Vol. 60 Special Issue on Recent Results from AKAR

Long-term monitoring of the short period SU UMa-type dwarf nova, V844 Herculis

We report on time-resolved CCD photometry of four outbursts of a short-period SU UMa-type dwarf nova, V844 Herculis. We successfully determined the mean superhump periods to be 0.05584(64) days, and 0.055883(3) for the 2002 May superoutburst, and the 2006 April-May superoutburst, respectively. During the 2002 October observations, we confirmed that the outburst is a normal outburst, which is the first recorded normal outburst in V844 Her. We also examined superhump period changes during 2002 May and 2006 April-May superoutbursts, both of which showed increasing superhump period over the course of the plateau stage. In order to examine the long-term behavior of V844 Her, we analyzed archival data over the past ten years since the discovery of this binary. Although photometry is not satisfactory in some superoutbursts, we found that V844 Her showed no precursors and rebrightenings. Based on the long-term light curve, we further confirmed V844 Her has shown almost no normal outbursts despite the fact that the supercycle of the system is estimated to be about 300 days. In order to explain the long-term light curves of V844 Her, evaporation in the accretion disk may play a role in the avoidance of several normal outbursts, which does not contradict with the relatively large X-ray luminosity of V844 Her.Comment: 10 pages, 11 figures, accepted for PAS

Regulation of functional KCNQ1OT1 lncRNA by β-catenin.

Long noncoding RNAs (lncRNAs) have been implicated in many biological processes through epigenetic mechanisms. We previously reported that KCNQ1OT1, an imprinted antisense lncRNA in the human KCNQ1 locus on chromosome 11p15.5, is involved in cis-limited silencing within an imprinted KCNQ1 cluster. Furthermore, aberration of KCNQ1OT1 transcription was observed with a high frequency in colorectal cancers. However, the molecular mechanism of the transcriptional regulation and the functional role of KCNQ1OT1 in colorectal cancer remain unclear. Here, we show that the KCNQ1OT1 transcriptional level was significantly increased in human colorectal cancer cells in which β-catenin was excessively accumulated in the nucleus. Additionally, overexpression of β-catenin resulted in an increase in KCNQ1OT1 lncRNA-coated territory. On the other hand, knockdown of β-catenin resulted in significant decrease of KCNQ1OT1 lncRNA-coated territory and an increase in the mRNA expression of the SLC22A18 and PHLDA2 genes that are regulated by KCNQ1OT1. We showed that β-catenin can promote KCNQ1OT1 transcription through direct binding to the KCNQ1OT1 promoter. Our evidence indicates that β-catenin signaling may contribute to development of colorectal cancer by functioning as a novel lncRNA regulatory factor via direct targeting of KCNQ1OT1

Activation of protein phosphatase 2A by cAMP-dependent protein kinase-catalyzed phosphorylation of the 74-kDa B″ (δ) regulatory subunit in vitro and identification of the phosphorylation sites

AbstractHuman erythrocyte protein phosphatase 2A, which comprises a 34-kDa catalytic C subunit, a 63-kDa regulatory A subunit and a 74-kDa regulatory B″ (δ) subunit, was phosphorylated at serine residues of B″ in vitro by cAMP-dependent protein kinase (A-kinase). In the presence and absence of 0.5 μM okadaic acid (OA), A-kinase gave maximal incorporation of 1.7 and 1.0 mol of phosphate per mol of B″, respectively. The Km value of A-kinase for CAB″ was 0.17±0.01 μM in the presence of OA. The major in vitro phosphorylation sites of B″ were identified as Ser-60, -75 and -573 in the presence of OA, and Ser-75 and -573 in the absence of OA. Phosphorylation of B″ did not dissociate B″ from CA, and stimulated the molecular activity of CAB″ toward phosphorylated H1 and H2B histones, 3.8- and 1.4-fold, respectively, but not toward phosphorylase a

The Heterochromatin Block That Functions as a Rod Cell Microlens in Owl Monkeys Formed within a 15-Myr Time Span

In rod cells of many nocturnal mammals, heterochromatin localizes to the central region of the nucleus and serves as a lens to send light efficiently to the photoreceptor region. The genus Aotus (owl monkeys) is commonly considered to have undergone a shift from diurnal to nocturnal lifestyle. We recently demonstrated that rod cells of the Aotus species Aotus azarae possess a heterochromatin block at the center of its nucleus. The purpose of the present study was to estimate the time span in which the formation of the heterochromatin block took place. We performed three-dimensional hybridization analysis of the rod cell of another species, Aotus lemurinus. This analysis revealed the presence of a heterochromatin block that consisted of the same DNA components as those in A. azarae. These results indicate that the formation was complete at or before the separation of the two species. Based on the commonly accepted evolutionary history of New World monkeys and specifically of owl monkeys, the time span for the entire formation process was estimated to be 15 Myr at most