tbuckley/cabot-search huggingface dataset:
OP0076 Kidneys of autoimmune nzb/w mice contain long-lived pc
Authors: AH Radbruch, G Cassese, S Lindenau, B De Boer, S Arce, A Hauser, G Riemekasten, C Berek, F Hiepe, RA Manz
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> NZB/W mice develop a disease similar to human systemic lupus erythematosus (SLE), including autoantibody production, hypergammaglobulinaemia and inflammation of the kidneys. Large numbers of lymphocytes infiltrate the kidneys of these mice but the role of this organ for the production of antibodies is not clear. <h3>Objectives</h3> Here, we compare the role of bone marrow, spleen and inflamed kidneys of NZB/W mice for the activation of B cells and for the persistence of antibody secreting cells (ASC). <h3>Methods</h3> NZB/W mice were immunised i.p.i with Ovalbumin and then boosted 1 month later. The number of antigen-specific PC present in spleen, bone marrow and kidneys was determined by Elispot. The frequency of different cell types was determined by flow-cytometry. The distribution of PC in the different organs was investigated by microscopy. <h3>Results</h3> ASC are present in the kidneys of mice with full blown disease, as many as in the spleen and bone marrow, and 50 times more than in the kidneys of normal mice. In the kidneys, ASC are located mainly in the outer medulla, close to B- and T cell infiltrates. The specificity of the ASC in the inflamed kidneys is not restricted to self-antigens. After immunisation of NZB/W mice with Ovalbumin (OVA), the antigen-specific ASC are found initially exclusively in the spleen. Weeks later, during a period of at least 3 month, OVA-specific ASC are found in stable and high numbers within the bone marrow and the kidneys of these mice, but no longer in the spleen. As determined by FACS, B cells with a germinal centre phenotype (B220+/PNA+) are found only in very low numbers in the kidneys, but in high numbers in the spleen of NZB/W mice. Germinal centres could not be detected in the kidneys, but in the spleen. The lack of B cell activation and the kinetics of the appearance of OVA-specific ASC in the kidneys suggest that in autoimmune NZB/W mice, plasma cells generated during an immune reaction in secondary lymphoid organs, later accumulate and persist in the inflamed kidneys, like in bone marrow. <h3>Conclusion</h3> These experiments identify the inflamed kidneys of NZB/W mice as site of prime relevance for the homeostasis of plasma cells, irrespective of their specificity.
Double-hit Signature with <i>TP53</i> Abnormalities Predicts Poor Survival in Patients with Germinal Center Type Diffuse Large B-cell Lymphoma Treated with R-CHOP
Authors: Joo Y. Song, Anamarija M. Perry, Alex F. Herrera, Lu Chen, Pamela Skrabek, Michel R. Nasr, Rebecca A. Ottesen, Janet Nikowitz, Victoria Bedell, Joyce Murata-Collins, Yuping Li, Christine McCarthy, Raju Pillai, Jinhui Wang, Xiwei Wu, Jasmine Zain, Leslie Popplewell, Larry W. Kwak, Auayporn P. Nademanee, Joyce C. Niland, David W. Scott, Qiang Gong, Wing C. Chan, Dennis D. Weisenburger
Journal: Clinical Cancer Research (2021)

Abstract Purpose: We performed detailed genomic analysis on 87 cases of de novo diffuse large B-cell lymphoma of germinal center type (GCB DLBCL) to identify characteristics that are associated with survival in those treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Experimental Design: The cases were extensively characterized by combining the results of IHC, cell-of-origin gene expression profiling (GEP; NanoString), double-hit GEP (DLBCL90), FISH cytogenetic analysis for double/triple-hit lymphoma, copy-number analysis, and targeted deep sequencing using a custom mutation panel of 334 genes. Results: We identified four distinct biologic subgroups with different survivals, and with similarities to the genomic classifications from two large retrospective studies of DLBCL. Patients with the double-hit signature, but no abnormalities of TP53, and those lacking EZH2 mutation and/or BCL2 translocation, had an excellent prognosis. However, patients with an EZB-like profile had an intermediate prognosis, whereas those with TP53 inactivation combined with the double-hit signature had an extremely poor prognosis. This latter finding was validated using two independent cohorts. Conclusions: We propose a practical schema to use genomic variables to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies.
Adverse events of interest following influenza vaccination, a comparison of cell culture-based with egg-based alternatives: English sentinel network annual report paper 2019/20
Authors: Simon de Lusignan, Ruby S.M. Tsang, Gayatri Amirthalingam, Oluwafunmi Akinyemi, Julian Sherlock, Manasa Tripathy, Alexandra Deeks, Filipa Ferreira, Gary Howsam, F.D.Richard Hobbs, Mark Joy
Journal: The Lancet Regional Health - Europe (2021)

The cell-based quadrivalent influenza vaccine (QIVc) is now offered as an alternative to egg-based quadrivalent (QIVe) and adjuvanted trivalent (aTIV) influenza vaccines in the UK. While post-licensure studies show non-inferiority of cell-based vaccines, it is not known how its safety profile compares to other types of vaccines in real-world use.We conducted a retrospective cohort study using computerised medical records from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network database. We used a self-controlled case series design and calculated the relative incidence (RI) of adverse events of interest (AEIs) over different risk periods. We then compared the RIs of AEIs within seven days of vaccination overall and between QIVc and QIVe in the 18-64 years age group, and between QIVc and aTIV in the ≥65 years age group.The majority of AEIs occurred within seven days of vaccination, and a seasonal effect was observed. Using QIVc as the reference group, QIVe showed similar incidence of AEIs whereas live attenuated influenza vaccine (LAIV) and aTIV had lower incidence of AEIs. In the stratified analyses, QIVe and aTIV were associated with a 16% lower incidence of AEIs in the seven days post-vaccination in both the 18-64 years and ≥65 years age groups.Routine sentinel network data allow comparisons of safety profiles of equally suitable seasonal influenza vaccines. The higher incidence of AEIs associated with QIVc suggest monitoring of several seasons would allow robust comparisons to be made.Public Health England.
Alda-1 treatment promotes the therapeutic effect of mitochondrial transplantation for myocardial ischemia-reperfusion injury
Authors: Xiaolei Sun, Rifeng Gao, Wenjia Li, Yongchao Zhao, Heng Yang, Hang Chen, Hao Jiang, Zhen Dong, Jingjing Hu, Jin Liu, Yunzeng Zou, Aijun Sun, Junbo Ge
Journal: Bioactive Materials (2021)

Mitochondrial damage is a critical driver in myocardial ischemia-reperfusion (I/R) injury and can be alleviated via the mitochondrial transplantation. The efficiency of mitochondrial transplantation is determined by mitochondrial vitality. Because aldehyde dehydrogenase 2 (ALDH2) has a key role in regulating mitochondrial homeostasis, we aimed to investigate its potential therapeutic effects on mitochondrial transplantation via the use of ALDH2 activator, Alda-1. Our present study demonstrated that time-dependent internalization of exogenous mitochondria by cardiomyocytes along with ATP production were significantly increased in response to mitochondrial transplantation. Furthermore, Alda-1 treatment remarkably promoted the oxygen consumption rate and baseline mechanical function of cardiomyocytes caused by mitochondrial transplantation. Mitochondrial transplantation inhibited cardiomyocyte apoptosis induced by the hypoxia-reoxygenation exposure, independent of Alda-1 treatment. However, promotion of the mechanical function of cardiomyocytes exposed to hypoxia-reoxygenation treatment was only observed after mitochondrial Alda-1 treatment and transplantation. By using a myocardial I/R mouse model, our results revealed that transplantation of Alda-1-treated mitochondria into mouse myocardial tissues limited the infarction size after I/R injury, which was at least in part due to increased mitochondrial potential-mediated fusion. In conclusion, ALDH2 activation in mitochondrial transplantation shows great potential for the treatment of myocardial I/R injury.
Histone demethylase JMJD3 protects against renal fibrosis by suppressing TGFβ and Notch signaling and preserving PTEN expression
Authors: Chao Yu, Chongxiang Xiong, Jinhua Tang, Xiying Hou, Na Liu, George Bayliss, Shougang Zhuang
Journal: Theranostics (2021)

Rationale: The Jumonji domain containing-3 (JMJD3), a specific histone demethylase for trimethylation on histone H3 lysine 27 (H3K27me3), is associated with the pathogenesis of many diseases, but its role in renal fibrosis remains unexplored. Here we examined the role of JMJD3 and mechanisms involved in the activation of renal fibroblasts and development of renal fibrosis. Methods: Murine models of 5/6 surgical nephrectomy (SNx) and ureteral unilateral obstruction (UUO) were used to assess the effect of a specific JMJD3 inhibitor, GSKJ4, and genetic deletion of JMJD3 from FOXD1 stroma-derived renal interstitial cells on the development of renal fibrosis and activation of renal interstitial fibroblasts. Cultured rat renal interstitial fibroblasts (NRK-49F) and mouse renal tubular epithelial cells (mTECs) were also used to examine JMJD3-mediated activation of profibrotic signaling. Results: JMJD3 and H3K27me3 expression levels were upregulated in the kidney of mice subjected to SNx 5/6 and UUO. Pharmacological inhibition of JMJD3 with GSKJ4 or genetic deletion of JMJD3 led to worsening of renal dysfunction as well as increased deposition of extracellular matrix proteins and activation of renal interstitial fibroblasts in the injured kidney. This was coincident with decreased expression of Smad7 and enhanced expression of H3K27me3, transforming growth factor β1 (TGFβ1), Smad3, Notch1, Notch3 and Jagged1. Inhibition of JMJD3 by GSK J4 or its specific siRNA also resulted in the similar responses in cultured NRK-49F and mTECs exposed to serum or TGFβ1. Moreover, JMJD3 inhibition augmented phosphorylation of AKT and ERK1/2 in vivo and in vitro. Conclusion: These results indicate that JMJD3 confers anti-fibrotic effects by limiting activation of multiple profibrotic signaling pathways and suggest that JMJD3 modulation may have therapeutic effects for chronic kidney disease.
A Spatial and Functional Interaction of a Heterotetramer Survivin–DNA-PKcs Complex in DNA Damage Response
Authors: Ömer Güllülü, Stephanie Hehlgans, Benjamin E. Mayer, Ines Gößner, Chrysi Petraki, Melanie Hoffmann, Maximilian J. Dombrowsky, Patrick Kunzmann, Kay Hamacher, Klaus Strebhardt, Emmanouil Fokas, Claus Rödel, Christian Münch, Franz Rödel
Journal: Cancer Research (2021)

Abstract Substantial evidence has shown that overexpression of the inhibitor of apoptosis protein (IAP) survivin in human tumors correlates significantly with treatment resistance and poor patient prognosis. Survivin serves as a radiation resistance factor that impacts the DNA damage response by interacting with DNA-dependent protein kinase (DNA-PKcs). However, the complexity, molecular determinants, and functional consequences of this interrelationship remain largely unknown. By applying coimmunoprecipitation and flow cytometry-based Förster resonance energy transfer assays, we demonstrated a direct involvement of the survivin baculovirus IAP repeat domain in the regulation of radiation survival and DNA repair. This survivin-mediated activity required an interaction of residues S20 and W67 with the phosphoinositide 3-kinase (PI3K) domain of DNA-PKcs. In silico molecular docking and dynamics simulation analyses, in vitro kinase assays, and large-scale mass spectrometry suggested a heterotetrameric survivin–DNA-PKcs complex that results in a conformational change within the DNA-PKcs PI3K domain. Overexpression of survivin resulted in enhanced PI3K enzymatic activity and detection of differentially abundant phosphopeptides and proteins implicated in the DNA damage response. The survivin–DNA-PKcs interaction altered the S/T-hydrophobic motif substrate specificity of DNA-PKcs with a predominant usage of S/T-P phosphorylation sites and an increase of DNA-PKcs substrates including Foxo3. These data demonstrate that survivin differentially regulates DNA-PKcs-dependent radiation survival and DNA double-strand break repair via formation of a survivin–DNA-PKcs heterotetrameric complex. Significance: These findings provide insight into survivin-mediated regulation of DNA-PKcs kinase and broaden our knowledge of the impact of survivin in modulating the cellular radiation response. See related commentary by Iliakis, p. 2270
Combined SHPments: An Effective Therapeutic Strategy for MPNST
Authors: Andrew E. Aplin, Claudia Capparelli
Journal: Cancer Research (2021)

Abstract Targeted therapies have provided the foundation for many advances in the treatment options for patients with late-stage cancer, however, adaptive and compensatory responses frequently limit their efficacy. Rational combinations of targeted inhibitors are being actively tested in preclinical models to form the basis for more durable responses in patients. In a previous issue, Wang and colleagues provide evidence that phosphorylated SHP2 is adaptively upregulated in response to MEK inhibitors in malignant peripheral nerve sheath tumors (MPNST) that have lost NF1 expression. The authors provide evidence that the combination of SHP2 inhibitors with MEK inhibitors has strong efficacy in preclinical MPNST models and propose that this targeted therapy combination should be rapidly translated. See related article by Wang et al.; Cancer Res 80(23):5367–79.
Human ISL1+ Ventricular Progenitors Self-Assemble into an In Vivo Functional Heart Patch and Preserve Cardiac Function Post Infarction
Authors: Kylie S. Foo, Miia L. Lehtinen, Chuen Yan Leung, Xiaojun Lian, Jiejia Xu, Wendy Keung, Lin Geng, Terje R.S. Kolstad, Sebastian Thams, Andy On-tik Wong, Nicodemus Wong, Kristine Bylund, Chikai Zhou, Xiaobing He, Shao-Bo Jin, Jonathan Clarke, Urban Lendahl, Ronald A. Li, William E. Louch, Kenneth R. Chien
Journal: Molecular Therapy (2020)

(Mol Ther. 26, 1644–1659; July 5, 2018) In the originally published version of this article, the authors overlooked including a funding source in the Acknowledgements section. This work was also supported by a grant to K.R.C from the European Research Council Advanced Research Grant Award (AdG743225) The authors regret this error. Human ISL1+ Ventricular Progenitors Self-Assemble into an In Vivo Functional Heart Patch and Preserve Cardiac Function Post InfarctionFoo et al.Molecular TherapyFebruary 17, 2018In BriefThe authors identified a human ventricular progenitor (HVP) population that can expand, differentiate, self-assemble, and mature into a 3D functional ventricular patch in vivo. They demonstrate that transplantation of HVPs under the kidney capsule generated a 7 mm × 3 mm × 4 mm myocardial patch while transplantation following myocardial infarction can largely preserve myocardial contractile function. Full-Text PDF Open Access
STIM1 Mediates Calcium-Dependent Epigenetic Reprogramming in Pancreatic Cancer
Authors: Ana P. Kutschat, Feda H. Hamdan, Xin Wang, Alexander Q. Wixom, Zeynab Najafova, Christine S. Gibhardt, Waltraut Kopp, Jochen Gaedcke, Philipp Ströbel, Volker Ellenrieder, Ivan Bogeski, Elisabeth Hessmann, Steven A. Johnsen
Journal: Cancer Research (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) displays a dismal prognosis due to late diagnosis and high chemoresistance incidence. For advanced disease stages or patients with comorbidities, treatment options are limited to gemcitabine alone or in combination with other drugs. While gemcitabine resistance has been widely attributed to the levels of one of its targets, RRM1, the molecular consequences of gemcitabine resistance in PDAC remain largely elusive. Here we sought to identify genomic, epigenomic, and transcriptomic events associated with gemcitabine resistance in PDAC and their potential clinical relevance. We found that gemcitabine-resistant cells displayed a coamplification of the adjacent RRM1 and STIM1 genes. Interestingly, RRM1, but not STIM1, was required for gemcitabine resistance, while high STIM1 levels caused an increase in cytosolic calcium concentration. Higher STIM1-dependent calcium influx led to an impaired endoplasmic reticulum stress response and a heightened nuclear factor of activated T-cell activity. Importantly, these findings were confirmed in patient and patient-derived xenograft samples. Taken together, our study uncovers previously unknown biologically relevant molecular properties of gemcitabine-resistant tumors, revealing an undescribed function of STIM1 as a rheostat directing the effects of calcium signaling and controlling epigenetic cell fate determination. It further reveals the potential benefit of targeting STIM1-controlled calcium signaling and its downstream effectors in PDAC. Significance: Gemcitabine-resistant and some naïve tumors coamplify RRM1 and STIM1, which elicit gemcitabine resistance and induce a calcium signaling shift, promoting ER stress resistance and activation of NFAT signaling.
Lactate Release By Bone Marrow Neutrophils Promotes Their Inflammatory Mobilization Via Endothelial GPR81 Signaling
Authors: Eman Khatib-Massalha, Anju Kumari, Karin Golan, Hassan Massalha, Francesca Avemaria, Shiri Gur-Cohen, Tomer Itkin, Orit Kollet, Abraham Avigdor, Asaf Spiegel, Stefan Offermanns, Ronen Alon, Amiram Ariel, Tsvee Lapidot
Journal: Blood (2017)
Early Interdisciplinary Supportive Care in Patients With Previously Untreated Metastatic Esophagogastric Cancer: A Phase III Randomized Controlled Trial
Authors: Zhihao Lu, Yu Fang, Chang Liu, Xiaotian Zhang, Xiaowei Xin, Yi He, Yanshuo Cao, Xi Jiao, Tianqi Sun, Ying Pang, Yanli Wang, Jun Zhou, Changsong Qi, Jifang Gong, Xicheng Wang, Jian Li, Lili Tang, Lin Shen
Journal: Journal of Clinical Oncology (2021)

Effective interventions to improve prognosis in metastatic esophagogastric cancer (EGC) are urgently needed. We assessed the effect of the early integration of interdisciplinary supportive care for patients with metastatic EGC on overall survival (OS).
Interventions to reduce the public health burden of gambling-related harms: a mapping review
Authors: Lindsay Blank, Susan Baxter, Helen Buckley Woods, Elizabeth Goyder
Journal: The Lancet Public Health (2021)

Recognition is growing that gambling, although highly profitable for corporations and governments, is a source of serious and unevenly distributed harm. This recognition has led to demands for public health strategies at the local, national, and international levels. We aimed to identify review-level evidence for interventions to address or prevent gambling-related harms and explore policy implications, using stakeholder consultation to assess the evidence base, identify gaps, and suggest key research questions. We opted for a systematic mapping review and narrative synthesis for all forms of gambling in any setting. We included participants from the whole population, identified gamblers including self-defined, and specific populations at risk (eg, children and young people). We included all outcome measures relating to prevention or treatment of gambling-related harms that were reported by review authors. After duplication, the searches generated 1080 records. Of 43 potential papers, 13 were excluded at the full paper stage and 30 papers were included in the Review. We identified whole-population preventive interventions, such as demand reduction (n=3) and supply reduction (n=4) interventions, and targeted treatment interventions for individuals addicted to gambling, such as therapeutic (n=12), pharmacological (n=5), and self-help or mutual support (n=4) interventions. We also reviewed studies (n=2) comparing these approaches. Interventions to screen, identify, and support individuals at risk of gambling-related harms and interventions to support ongoing recovery and prevent relapse for individuals with a gambling addiction were not represented in the review-level evidence. A public health approach suggests that there are opportunities to reduce gambling-related harms by intervening across the whole gambling pathway, from regulation of access to gambling to screening for individuals at risk and services for individuals with an identified gambling problem. The dearth of evidence for some interventions means that implementation must be accompanied by robust evaluation.
Abstract 16048: Young Women Post-MI Have Higher Levels of Inflammation Before and After Stress Testing
Authors: Cherie R Rooks, Amit J Shah, Ijeom Ibeanu, Pratik Pimple, Nancy Murrah, Thaddeus Pace, J. Douglas Bremner, Paolo Raggi, Viola Vaccarino
Journal: Circulation (2013)

Objectives: Young women have poorer prognosis after myocardial infarction (MI) compared with similarly aged men. Inflammatory responses to mental and physical stress may help explain these sex diff...
Natural History and Hepatocellular Carcinoma Risk in Untreated Chronic Hepatitis B Patients With Indeterminate Phase
Authors: Daniel Q. Huang, Xiaohe Li, Michael H. Le, An K. Le, Yee Hui Yeo, Huy N. Trinh, Jian Zhang, Jiayi Li, Christopher Wong, Clifford Wong, Ramsey C. Cheung, Hwai-I Yang, Mindie H. Nguyen
Journal: Clinical Gastroenterology and Hepatology (2021)
In severe COVID-19, adding lopinavir–ritonavir to usual care did not improve mortality at 28 days
Authors: Ameeta Singh
Journal: Annals of Internal Medicine (2021)

RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2020;396:1345-52. 33031764.
Acetyl-CoA Synthetase 2: A Critical Linkage in Obesity-Induced Tumorigenesis in Myeloma
Authors: Zongwei Li, Huan Liu, Jin He, Zhiqiang Wang, Zheng Yin, Gichun You, Zhiming Wang, Richard E. Davis, Pei Lin, P. Leif Bergsagel, Elisabet E. Manasanch, Stephen T.C. Wong, Nestor F. Esnaola, Jenny C. Chang, Robert Z. Orlowski, Qing Yi, Jing Yang
Journal: Cell Metabolism (2021)
Abstract 14784: The Structural and Social Determinants of Differences in Non-Adherence to Antihypertensive Medications Between Blacks and Whites
Authors: Macarius M Donneyong, Teng-Jen Chang, Shawnita Sealy-Jefferson, John Jackson, JaNelle Ricks, Paul D uarez, Pamela Salsberry, Robert Otto Valdez, Bo Lu, Wansoo Im, Michael Langston, Darryl B. Hood, Michael Fischer
Journal: Circulation (2019)

Introduction: The sources of black-white differences in nonadherence to antihypertensive medications (AHM) are not well understood. Structural and social determinants of health (SDH) have been link...
Mixed Findings in Pediatric Neuroblastoma CAR-T Therapy Trial
Authors: Jennifer Abbasi
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal