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51.
Kun Yang Jie Han Mayumi Asada Jennifer G. Gill Jason Y. Park Meghana N. Sathe Jyothsna Gattineni Tracey Wright Christian A. Wysocki M. Teresa de la Morena Luis A. Garza Nan Yan 《The Journal of clinical investigation》2022,132(2)
Inborn errors of nucleic acid metabolism often cause aberrant activation of nucleic acid sensing pathways, leading to autoimmune or autoinflammatory diseases. The SKIV2L RNA exosome is cytoplasmic RNA degradation machinery that was thought to be essential for preventing the self-RNA–mediated interferon (IFN) response. Here, we demonstrate the physiological function of SKIV2L in mammals. We found that Skiv2l deficiency in mice disrupted epidermal and T cell homeostasis in a cell-intrinsic manner independently of IFN. Skiv2l-deficient mice developed skin inflammation and hair abnormality, which were also observed in a SKIV2L-deficient patient. Epidermis-specific deletion of Skiv2l caused hyperproliferation of keratinocytes and disrupted epidermal stratification, leading to impaired skin barrier with no appreciable IFN activation. Moreover, Skiv2l-deficient T cells were chronically hyperactivated and these T cells attacked lesional skin as well as hair follicles. Mechanistically, SKIV2L loss activated the mTORC1 pathway in both keratinocytes and T cells. Both systemic and topical rapamycin treatment of Skiv2l-deficient mice ameliorated epidermal hyperplasia and skin inflammation. Together, we demonstrate that mTORC1, a classical nutrient sensor, also senses cytoplasmic RNA quality control failure and drives autoinflammatory disease. We also propose SKIV2L-associated trichohepatoenteric syndrome (THES) as a new mTORopathy for which sirolimus may be a promising therapy. 相似文献
52.
Mayumi Ishida Hideki Onishi Tatsuya Morita Yosuke Uchitomi Megumi Shimizu Satoru Tsuneto Yasuo Shima Mitsunori Miyashita 《Journal of pain and symptom management》2018,55(4):1061-1067.e1
Context
The importance of communication between the cancer bereaved and others has been emphasized, but little is known about the more problematic aspects of this communication such as “unhelpful communication.”Objectives
The aim of this study was to establish which types of communication are perceived by the bereaved to be unhelpful.Methods
We conducted a cross-sectional, anonymous, nationwide survey at 103 certified hospice facilities/palliative care units in Japan.Results
A total of 630 (63%) bereaved responded. Over 60% of the bereaved experiencing such communication considered it to be unhelpful, with the most unhelpful communication being “They emphasized the positive aspects of death.” Thirteen items related to communication were separated into two factors (“advice for recovery” and “comments on cancer”) by factor analysis. “Comments on cancer” were more unhelpful to them and were more often provided by those around them. With regard to “advice for recovery,” losing a spouse was a stronger predictor with a higher odds ratio for communication distress than losing a parent (odds ratio, 5.34; 95% CI, 1.63–17.57).Conclusion
A number of the bereaved have experienced unhelpful communication regarding advice on dealing with bereavement and cancer. To prevent putting an unnecessary burden on the bereaved with such unhelpful communication, it is essential to understand problematic aspects. Even when people have no intention of hurting the bereaved, some communication may do so. Communication with the bereaved is also a core clinical skill required by health professionals, and further efforts are required to support the grieving process. 相似文献53.
Shigeki Kushimoto Satoshi Gando Daizoh Saitoh Toshihiko Mayumi Hiroshi Ogura Seitaro Fujishima Tsunetoshi Araki Hiroto Ikeda Joji Kotani Yasuo Miki Shin-ichiro Shiraishi Koichiro Suzuki Yasushi Suzuki Naoshi Takeyama Kiyotsugu Takuma Ryosuke Tsuruta Yoshihiro Yamaguchi Norio Yamashita Naoki Aikawa 《Critical care (London, England)》2013,17(6):R271
Introduction
Abnormal body temperatures (Tb) are frequently seen in patients with severe sepsis. However, the relationship between Tb abnormalities and the severity of disease is not clear. This study investigated the impact of Tb on disease severity and outcomes in patients with severe sepsis.Methods
We enrolled 624 patients with severe sepsis and grouped them into 6 categories according to their Tb at the time of enrollment. The temperature categories (≤35.5°C, 35.6–36.5°C, 36.6–37.5°C, 37.6–38.5°C, 38.6–39.5°C, ≥39.6°C) were based on the temperature data of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring. We compared patient characteristics, physiological data, and mortality between groups.Results
Patients with Tb of ≤36.5°C had significantly worse sequential organ failure assessment (SOFA) scores when compared with patients with Tb >37.5°C on the day of enrollment. Scores for APACHE II were also higher in patients with Tb ≤35.5°C when compared with patients with Tb >36.5°C. The 28-day and hospital mortality was significantly higher in patients with Tb ≤36.5°C. The difference in mortality rate was especially noticeable when patients with Tb ≤35.5°C were compared with patients who had Tb of >36.5°C. Although mortality did not relate to Tb ranges of ≥37.6°C as compared to reference range of 36.6–37.5°C, relative risk for 28-day mortality was significantly greater in patients with 35.6–36.5°C and ≤35.5°C (odds ratio; 2.032, 3.096, respectively). When patients were divided into groups based on the presence (≤36.5°C, n = 160) or absence (>36.5°C, n = 464) of hypothermia, disseminated intravascular coagulation (DIC) as well as SOFA and APACHE II scores were significantly higher in patients with hypothermia. Patients with hypothermia had significantly higher 28-day and hospital mortality rates than those without hypothermia (38.1% vs. 17.9% and 49.4% vs. 22.6%, respectively). The presence of hypothermia was an independent predictor of 28-day mortality, and the differences between patients with and without hypothermia were observed irrespective of the presence of septic shock.Conclusions
In patients with severe sepsis, hypothermia (Tb ≤36.5°C) was associated with increased mortality and organ failure, irrespective of the presence of septic shock.Trial registration
UMIN-CTR ID UMIN000008195 相似文献54.
55.
This study assessed the antimalarial activity of dipyridamole, a well-known vasodilator and inhibitor of platelet aggregation. Dipyridamole was effective against all of the erythrocytic stages such as rings, trophozoites and schizonts, and induced ultrastructural changes during the transition from trophozoite to schizont in vitro. Merozoites were also inhibited from invading dipyridamole-treated erythrocytes. It seems that dipyridamole binds to the erythrocyte membrane blocking the receptors for the merozoite. The 50% inhibitory concentration (IC(50)) of dipyridamole against Plasmodium falciparum infection was 30 nM. The IC(50) of chloroquine decreased from 97.0 nM to 13.7 nM when combined with dipyridamole (0.1 nM). Therefore, we suggest that dipyridamole has antiplasmodial activity due to its ability to arrest parasite development and by inhibiting merozoite invasion of the erythrocytes. Chloroquine activity against P. falciparum is also enhanced by the addition of dipyridamole. Treatment with a combination of chloroquine and dipyridamole may lead to a more effective treatment for chloroquine-resistant strains of P. falciparum. 相似文献
56.
Dennis M. de Graaf Martin Jaeger Inge C. L. van den Munckhof Rob ter Horst Kiki Schraa Jelle Zwaag Matthijs Kox Mayumi Fujita Takeshi Yamauchi Laura Mercurio Stefania Madonna Joost H.W. Rutten Jacqueline de Graaf Niels P. Riksen Frank L. van de Veerdonk Mihai G. Netea Leo A.B. Joosten Charles A. Dinarello 《European journal of immunology》2021,51(3):662-671
The IL-1 family member IL-38 (IL1F10) suppresses inflammatory and autoimmune conditions. Here, we report that plasma concentrations of IL-38 in 288 healthy Europeans correlate positively with circulating memory B cells and plasmablasts. IL-38 correlated negatively with age (p = 0.02) and was stable in 48 subjects for 1 year. In comparison with primary keratinocytes, IL1F10 expression in CD19+ B cells from PBMC was lower, whereas cell-associated IL-38 expression was comparable. In vitro, IL-38 is released from CD19+ B cells after stimulation with rituximab. Intravenous LPS in humans failed to induce circulating IL-38, compared to 100-fold induction of IL-6 and IL-1 receptor antagonist. In a cohort of 296 subjects with body mass index > 27 at high risk for cardiovascular disease, IL-38 plasma concentrations were significantly lower than in healthy subjects (p < 0.0001), and lowest in those with metabolic syndrome (p < 0.05). IL-38 also correlated inversely with high sensitivity C-reactive protein (p < 0.01), IL-6, IL-1Ra, and leptin (p < 0.05). We conclude that a relative deficiency of the B cell product IL-38 is associated with increased systemic inflammation in aging, cardiovascular and metabolic disease, and is consistent with IL-38 as an anti-inflammatory cytokine. 相似文献
57.
Unexpected mitochondrial matrix localization of Parkinson's disease‐related DJ‐1 mutants but not wild‐type DJ‐1 下载免费PDF全文
Waka Kojima Yuki Kujuro Kei Okatsu Queliconi Bruno Fumika Koyano Mayumi Kimura Koji Yamano Keiji Tanaka Noriyuki Matsuda 《Genes to cells : devoted to molecular & cellular mechanisms》2016,21(7):772-788
DJ‐1 has been identified as a gene responsible for recessive familial Parkinson's disease (familial Parkinsonism), which is caused by a mutation in the PARK7 locus. Consistent with the inferred correlation between Parkinson's disease and mitochondrial impairment, mitochondrial localization of DJ‐1 and its implied role in mitochondrial quality control have been reported. However, the mechanism by which DJ‐1 affects mitochondrial function remains poorly defined, and the mitochondrial localization of DJ‐1 is still controversial. Here, we show the mitochondrial matrix localization of various pathogenic and artificial DJ‐1 mutants by multiple independent experimental approaches including cellular fractionation, proteinase K protection assays, and specific immunocytochemistry. Localization of various DJ‐1 mutants to the matrix is dependent on the membrane potential and translocase activity in both the outer and the inner membranes. Nevertheless, DJ‐1 possesses neither an amino‐terminal alpha‐helix nor a predictable matrix‐targeting signal, and a post‐translocation processing‐derived molecular weight change is not observed. In fact, wild‐type DJ‐1 does not show any evidence of mitochondrial localization at all. Such a mode of matrix localization of DJ‐1 is difficult to explain by conventional mechanisms and implies a unique matrix import mechanism for DJ‐1 mutants. 相似文献
58.
59.
Hitoshi Otsuki Osamu Kaneko Amporn Thongkukiatkul Mayumi Tachibana Hideyuki Iriko Satoru Takeo Takafumi Tsuboi Motomi Torii 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(17):7167-7172
The major virulence determinant of the rodent malaria parasite, Plasmodium yoelii, has remained unresolved since the discovery of the lethal line in the 1970s. Because virulence in this parasite correlates with the ability to invade different types of erythrocytes, we evaluated the potential role of the parasite erythrocyte binding ligand, PyEBL. We found 1 amino acid substitution in a domain responsible for intracellular trafficking between the lethal and nonlethal parasite lines and, furthermore, that the intracellular localization of PyEBL was distinct between these lines. Genetic modification showed that this substitution was responsible not only for PyEBL localization but also the erythrocyte-type invasion preference of the parasite and subsequently its virulence in mice. This previously unrecognized mechanism for altering an invasion phenotype indicates that subtle alterations of a malaria parasite ligand can dramatically affect host–pathogen interactions and malaria virulence. 相似文献
60.
We report a case of congenital cystic adenomatoid malformation (CCAM) complicated by an esophageal duplication cyst in a 6-month-old girl. The patient presented with recurrent pneumonia. Magnetic resonance imaging revealed two cystic lesions in the upper and lower lobes of the right lung. After cystectomy, histopathological investigation revealed that the lower cyst was a CCAM Type I, and the upper cyst was an esophageal duplication cyst. The coexistence of these complex anomalies supports the concept that the esophageal duplication cyst is one entity of a broad spectrum of developmental abnormalities caused by abnormal budding of the primitive foregut. 相似文献