Tubulointerstitial nephritis complicating IVIG therapy for X-linked agammaglobulinemia

BACKGROUND: Patients with X-linked agammaglobulinemia (XLA) develop immune-complex induced diseases such as nephropathy only rarely, presumably because their immunoglobulin (Ig) G concentration is low. We encountered a patient with XLA who developed tubulointerstitial nephritis during treatment with intravenous immunoglobulin (IVIG). CASE PRESENTATION: A 20-year-old man was diagnosed with XLA 3 months after birth and subsequently received periodic γ-globulin replacement therapy. Renal dysfunction developed at 19 years of age in association with high urinary β2-microglobulin (MG) concentrations. A renal biopsy specimen showed dense CD3-positive lymphocytic infiltration in the tubulointerstitium and tubular atrophy, while no IgG4-bearing cell infiltration was found. Fibrosclerosis and crescent formation were evident in some glomeruli. Fluorescent antibody staining demonstrated deposition of IgG and complement component C3 in tubular basement membranes. After pulse steroid therapy was initiated, urinary β2-MG and serum creatinine concentrations improved. CONCLUSION: Neither drug reactions nor collagen disease were likely causes of tubular interstitial disorder in this patient. Although BK virus was ruled out, IgG in the γ-globulin preparation might have reacted with a pathogen present in the patient to form low-molecular-weight immune complexes that were deposited in the tubular basement membrane

Development of an adiabatic demagnetization refrigerator for X-ray microcalorimeter operations

金沢大学理工研究域数物科学系An X-ray microcalorimeter is a non-dispersive spectrometer that measures the energy of an incident X-ray photon as a temperature rise. Operated at < 0.1 K, it achieves very high resolving power. We are developing X-ray microcalorimeters for future γ-ray burst observations, and are now setting up a compact adiabatic demagnetization refrigerator (ADR) for X-ray microcalorimeter operations. We fabricated a paramagnetic salt pill, and integrated it with a superconducting magnet and a heat-switch in a dedicated He cryostat. By applying a magnetic field of 2.6 T at the bath temperature of 1.8 K, it achieved 0.1 K. The attainable temperature and the hold time were, however, limited due to unexpected heat load. We also successfully measured a resistance-temperature characteristics of a superconducting transition edge. © 2010 American Institute of Physics

Fall Risk Notification System using LiDAR Sensor for the Visually Impaired People

We have developed the fall risk notification system using LiDAR sensors to reduce number of fall accidents on platform involving visually impaired people. In this paper, we report the experiment results of the environment recognition algorithm for the fall risk notification system. In this algorithm, height grid map is generated from the depth image from LiDAR sensor and the posture of iPhone. In the experiment, we evaluated the accuracy and responsivity when approaching risky area of falling, such as stairs.The 2022 International Conference on Artificial Life and Robotics (ICAROB 2022), January 20-23, 2022, on line, Oita, Japa

Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms

Validity of the Short Nutritional Assessment Questionnaire for Japanese Patients with Cancer Undergoing Outpatient Chemotherapy

Purpose : To investigate the utility of the Short Nutritional Assessment Questionnaire (SNAQ) in the nutritional evaluation of patients with cancer undergoing outpatient chemotherapy. Methods :We included 229 patients with cancer who were undergoing outpatient chemotherapy between October 2015 and April 2016. The SNAQ and the revised SNAQ (addition of age and body mass index) were implemented, and their relationships with Controlling Nutritional Status (CONUT), an indicator of bionutritional assessment, were examined. Results : The cutoff value of the SNAQ score corresponding to moderate-to-severe undernourishment in CONUT values was 0.5, with a sensitivity of 87.5% and a specificity of 65.9%, and the corresponding values for the revised SNAQ score were 2.5, 91.7%, and 62.9%, respectively. This cutoff value and the corresponding positive prediction value for the revised SNAQ were superior to those of SNAQ. Binary logistic regression analysis with the revised SNAQ and sex as independent variables and the CONUT value as the dependent variable revealed that the higher the SNAQ score, the more likely it was that CONUT moderate-to-severe undernourishment would be identified (odds ratio, 1.48 ; , 1.34-1.96) . Conclusion : Nutritional evaluation with the revised SNAQ can predict moderateto- severe undernourishment according to CONUT in patients with cancer undergoing outpatient chemotherapy

〈Cases Reports〉Recurrent focal intestinal perforation in extremely-low-birth-weight infant

[Abstract] In recent years, the incidence of focal intestinal perforation (FIP) has been increasing, as the survival rate of extremely-low-birth-weight(ELBW) infants has been rising. We present a case of an ELBW infant who suffered three recurrences of FIP in a very short period of time. The patient was a female infant who was born at 24 weeks and 2 days of gestation, with a birth weight of 579 g. On her 22^nd day of life, abdominal X-rays revealed free air, which suggested intestinal perforation, and an intraperitoneal drainage tube was placed. Intraperitoneal lavage was performed on day 28 of life,and the drained fluid was turbid with feces, suggesting a recurrence of perforation. On day 30 of life, laparotomy revealed a perforation of approximately 1cm in diameter located at 6 cm from the ileocecum on the oral side. The X-ray taken on day 34 again revealed free air, and, through another laparotomy, a new perforation was found at about 15 cm from the stoma on the oral side. This case provides suggestions that may shed light on our approach to determine the pathogenesis of FIP, especially since no other case of FIP recurring three times has ever been reported

A novel lophine-based fluorescence probe and its binding to human serum albumin

The binding of a lophine-based fluorescence probe, 4-[4-(4-dimethylaminophenyl)-5-phenyl-1H-imidazol-2-yl]benzoic acid methyl ester (DAPIM) with human serum albumin (HSA) was investigated by fluorescence spectroscopy under physiological conditions. While DAPIM shows extreme low fluorescence in aqueous solution, DAPIM binding with HSA emits strong fluorescence at 510nm. The binding constant and binding number determined by Scatchard plot was 3.65×106M-1 and 1.07, respectively. Competitive binding between DAPIM and other ligands such as warfarin, valproic acid, diazepam and oleic acid, were also studied fluorometrically. The results indicated that the primary binding site of DAPIM to HSA is site II at subdomain IIIA. DAPIM can be a useful fluorescence probe for the characterization of drug-binding sites. In addition to the interaction study, because the fluorescence intensity of DAPIM increased in proportion to HSA concentration, its potential in HSA assay for serum sample was also evaluated

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

ショウガク 1ネンセイ ニオケル ヨウチエン シュッシンシャ ト ホイクショ シュッシンシャ ノ エイヨウ セッシュ ジョウキョウ ノ ヒカク

京都市内の一小学校の1年生120名を対象者に, 6月の休日および平日各1日に摂取した全食品の摂食量の記録を保護者に依頼し, 回答のあった男子41名, 女子47名, 計88名(73.3%)の栄養素および食品群別摂取量を出身別に比較検討した。その結果, 幼稚園出身者が保育所出身者より有意に高値を示したのは, 男子の果実類摂取量, 女子の脂質摂取量, 脂肪エネルギー比率であった。その他の項目では出身別に有意な差は認めなかった。全体において, 推定平均必要量以下の者の割合は, カルシウムは男子56.1%, 女子55.3%, 鉄は男子29.3%, 女子27.7%, ビタミンCは男子34.1%, 女子31.9%, 脂肪エネルギー比率が30%以上の割合は男子61.0%, 女子63.8%, 食塩6g以上の割合は男子78.0%, 女子68.1%と高かった。これより, 小学1年生において出身別の差は少ないこと, カルシウム, 鉄の不足者割合が高く, 脂質及び食塩の摂取量が目標量を超える者の割合が多い可能性が示唆された