Immunohistochemical findings in the pancreatic islets of a patient with transfusional iron overload and diabetes : case report

Excessive iron storage sometimes causes diabetes in patients with hemochromatosis, a disease caused by iron overloading. We performed an immunohistochemical analysis to study an autopsy case of aplastic anemia and diabetic hemochromatosis caused by frequent blood transfusions, and extensive hemosiderin deposition was observed in the liver and pancreas. The pancreatic islets of the patient and a control subject were stained to detect glucagon, insulin, and proinsulin. Significantly lower levels of immunoreactivity with both insulin antibodies and proinsulin antibodies, but not with glucagon antibodies, was observed in the islet cells in the patient’s tissue than in the islet cells of the control. Hemosiderin deposition in the islets is known to be exclusively distributed in the β-cells, thus, selective iron-induced damage to the β-cells may have affected insulin synthesis and secretion and led to glucose intolerance in the patient

Amino Acid Synthesis in a Supercritical Carbon Dioxide - Water System

Mars is a CO2-abundant planet, whereas early Earth is thought to be also CO2-abundant. In addition, water was also discovered on Mars in 2008. From the facts and theory, we assumed that soda fountains were present on both planets, and this affected amino acid synthesis. Here, using a supercritical CO2/liquid H2O (10:1) system which mimicked crust soda fountains, we demonstrate production of amino acids from hydroxylamine (nitrogen source) and keto acids (oxylic acid sources). In this research, several amino acids were detected with an amino acid analyzer. Moreover, alanine polymers were detected with LC-MS. Our research lights up a new pathway in the study of life’s origin

Case of relapsed AIDS-related plasmablastic lymphoma treated with autologous stem cell transplantation and highly active antiretroviral therapy

Plasmablastic lymphoma is a rare and aggressive malignancy strongly associated with HIV infection. The refractory/relapsed disease rate is high, and the survival rate is characteristically poor. There are no satisfactory salvage regimens for relapsed cases. We successfully performed autologous stem cell transplantation using a regimen consisting of MCNU (ranimustine), etoposide, cytarabine, and melphalan in a Japanese patient with relapsed AIDS-related plasmablastic lymphoma of the oral cavity. Highly active antiretroviral therapy continued during the therapy. Therapy-related toxicity was tolerable, and a total of 40 Gy of irradiation was administered after autologous stem cell transplantation. The patient has remained in complete remission for 16 months since transplantation

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

Autopsy analysis may contribute to establish actual incidence of second primary malignancies in myeloma

Second primary malignancies (SPMs) are issues for patients with multiple myeloma (MM). There may have been some limitations in prior studies, such as difficulties in a longer follow-up and absence of established screening methods. Therefore, we studied autopsied cases to overcome these limitations. This study aimed to examine SPMs using autopsy reports. Ninety-one cases of MM autopsied at our institution from 1979 to 2013 were analyzed. Median age of autopsied patients was 64.1 years, and proportion of male/female was 59/32. Autopsy was performed in 35.3% of patients died of MM. There were five cases of SPMs with a median confirmation time of 38 (12-132) months from the diagnosis of MM. In three of the five patients, the diagnosis of SPMs was established at autopsy. One case was of myelodysplastic syndrome, and the others were of non-hematological malignancies. The annual risk of SPM estimated using the Kaplan-Meier method was approximately 1%. Three of five SPM cases were detected at autopsy. Analysis of autopsy may contribute to estimate the actual risk of SPMs in MM

A Longitudinal Study of Subjective Daytime Sleepiness Changes in Elementary School Children Following a Temporary School Closure Due to COVID-19

Excessive daytime sleepiness is increasingly being recognized as a major global health concern. However, there have been few studies related to sleepiness and its associated factors in elementary school children. In Japan, all schools were closed from February to May 2020 to prevent coronavirus disease 2019 (COVID-19) outbreaks. The aim of this study was to identify changes in the subjective sleepiness of pupils during the 1.5-year period and to elucidate factors associated with changes in sleepiness. Questionnaire surveys about pupils’ sleep habits and the Japanese version of the Pediatric Daytime Sleepiness Scale (PDSS-J) were conducted longitudinally at one elementary school in June 2019, January 2020, and June 2020. The average ∆PDSS score was 0.94 ± 5.51 (mean ± standard deviation) from June 2019 to January 2020 and −1.65 ± 5.71 (t[498] = 6.13, p p = 0.02) during the school closure. A less restrictive school schedule secondary to a COVID-19-related school closure decreased sleepiness in children and was associated with decreasing social jetlag