99 research outputs found

    Subocclusive thrombus at the origin of LSA

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    Optimal treatment of patients with intracranial subocclusive thrombus remains unclear. Such a rare case successfully managed with endovascular mechanical thrombectomy is presented. A 71-year-old man experienced a sudden onset of dysarthria and motor deficits. At the time of admission his National Institutes of Health Stroke Scale (NIHSS) score was 4. DWI demonstrated incomplete infarction within the left lenticulostriate artery (LSA) territory, MRA showed partial flow defect in the distal left M1 segment and non-visualization of the LSA, and ECG revealed atrial fibrillation, thus ischemic stroke caused by cardiogenic embolism was diagnosed. Tissue plasminogen activator was administered, but symptoms progressed and NIHSS score increased up to 8. Diagnostic angiogrpahy confirmed presence of the subocclusive thrombus within the distal left M1 segment and complete occlusion of LSA at its origin. Since conservative therapy was ineffective, mechanical thrombectomy utilizing ADAPT (a direct aspiration first-pass thrombectomy) technique was performed resulting in compete recanalization of the LSA accompanied by the prompt regress of neurological symptoms. Eventally, the patient demonstrated nearly full recovery (modified Rankin Scale score 1). Thus, mechanical thrombectomy should be considered as a reasonable option in cases of acute cerebral stroke caused by subocclusive thrombus and progressive neurological deficits despite standard conservative therapy

    Memory impairment caused by cerebral hematoma in the left medial temporal lobe due to ruptured posterior cerebral artery aneurysm

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    BACKGROUND: Cognitive disorders, such as memory disturbances, are often observed following a subarachnoid hemorrhage. We present a very rare case where rupture of a posterior cerebral artery aneurysm caused restricted damage to the hippocampus unilaterally, and caused memory disturbances. CASE PRESENTATION: A 56-year-old, right-handed man, with a formal education history of 16 years and company employees was admitted to our hospital because of a consciousness disturbance. He was diagnosed as having a subarachnoid hemorrhage due to a left posterior cerebral artery dissecting aneurysm, and coil embolization was performed. Subsequently, he had neither motor paresis nor sensory disturbances, but he showed disorientation, and both retrograde and anterograde amnesia. Although immediate recall and remote memory were almost intact, his recent memory was moderately impaired. Both verbal and non-verbal memories were impaired. Brain computed tomography (CT) and magnetic resonance imaging (MRI) revealed a cerebral hematoma in the left temporal lobe involving the hippocampus and parahippocampal gyrus, and single-photon emission computed tomography (SPECT) demonstrated low perfusion areas in the left medial temporal lobe. CONCLUSIONS: We suggest that the memory impairment was caused by local tissue destruction of Papez’s circuit in the dominant hemisphere due to the cerebral hematoma

    Specific Expression of Human Intelectin-1 in Malignant Pleural Mesothelioma and Gastrointestinal Goblet Cells

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    Malignant pleural mesothelioma (MPM) is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM

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

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    「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

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    「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

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    Search for single production of vector-like quarks decaying into Wb in pp collisions at s=8\sqrt{s} = 8 TeV with the ATLAS detector

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