tbuckley/cabot-search huggingface dataset:
Inhibition of NF-κB activation in macrophages increases atherosclerosis in LDL receptor–deficient mice
Authors: Edwin Kanters, Manolis Pasparakis, Marion J.J. Gijbels, Monique N. Vergouwe, Iris Partouns-Hendriks, Remond J.A. Fijneman, Björn E. Clausen, Irmgard Förster, Mark M. Kockx, Klaus Rajewsky, Georg Kraal, Marten H. Hofker, Menno P.J. de Winther
Journal: Journal of Clinical Investigation (2003)

Atherosclerosis is now generally accepted as a chronic inflammatory condition. The transcription factor NF-κB is a key regulator of inflammation, immune responses, cell survival, and cell proliferation. To investigate the role of NF-κB activation in macrophages during atherogenesis, we used LDL receptor–deficient mice with a macrophage-restricted deletion of IκB kinase 2 (IKK2), which is essential for NF-κB activation by proinflammatory signals. These mice showed increased atherosclerosis as quantified by lesion area measurements. In addition, the lesions were more advanced and showed more necrosis and increased cell number in early lesions. Southern blotting revealed that deletion of IKK2 was approximately 65% in macrophages, coinciding with a reduction of 50% in NF-κB activation, as compared with controls. In both groups, the expression of differentiation markers, uptake of bacteria, and endocytosis of modified LDL was similar. Upon stimulation with LPS, production of TNF was reduced by approximately 50% in IKK2-deleted macrophages. Interestingly, we also found a major reduction in the anti-inflammatory cytokine IL-10. Our data show that inhibition of the NF-κB pathway in macrophages leads to more severe atherosclerosis in mice, possibly by affecting the pro- and anti-inflammatory balance that controls the development of atherosclerosis.
SICKLE CELL ANEMIA AND THE EYE
Journal: JAMA (1963)

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
Abstract 19824: Molecular Regulation of Novel Pro-survival Bnip3 Spliced Variant Niplet in Cardiac Myocytes Functionally Couples Er and Mitochondria
Authors: Junjun Lin, Hongying Gang, Rimpy Dhingra, Lorrie A. Kirshenbaum
Journal: Circulation (2015)

Alternative splicing provides a versatile mechanism by which cells generate proteins with different or even antagonistic properties. Herein we describe a novel splice variant of the hypoxia-inducible death gene Bnip3. Sequence analysis of the new Bnip3 protein revealed an N-terminus that was identical to Bnip3 but contained an ER retention motif within the C-terminus, therefore we designated the new Bnip3 isoform NIPLET for ( N ip- L ike E R T arget). While Bnip3 was predominately localized to mitochondria and promoted mitochondrial perturbations and necrosis, NIPLET was preferentially localized to the ER and opposed the cytotoxic actions of Bnip3. Interestingly, NIPLET suppressed inter-organelle calcium transfer between ER and mitochondria and mitochondrial permeability transition pore opening by a mechanism dependent upon the dynamin motor protein Mitofusin-2 (MFN2). Notably, NIPLET mutations within in the critical ER retention motif rendered NIPLET defective for interacting with MFN2 and suppression of necrosis induced by Bnip3 or hypoxia. Hence, our findings reveal a novel signaling pathway that functionally couples ER and mitochondria for cell survival to a mechanism that is mutually dependent and obligatorily linked to a novel BNIP3 protein in cardiac myocytes.
Three Lectures on Tubercular Joint-Disease and its Treatment by Operation
Authors: A. E. J. Barker
Journal: BMJ (1888)

without the itching and the sensations of "pins and needles."louse dust will bring on an attack, bedroom dust and the (lust from shaking a bed being most potent.The dust of the street, curiously enough, does not affect her; indeed, she often expe- riences relief during a paroxysm from going out of doors.Flowers do not bring on the attacks, which cannot be due to hay, for she resides in a large city; they occur at all times of the y-ear.Sunlighlt will not excite the attack, although she complains that it hurts her eyes.She obtains some relief from taking food, hot tea, or port wine.Iler mother has been a sneezer all her life.A middle-aged man, an ironmonger, has suffered( from paroxysmal coryza and asthlma for two years, the attacks being induced only by the dust of his shop.Other kinds of dust, for example that of a road, fail to affect him, and flowers, grasses, and bright sunlight are innocuous.The case is peculiar in this respect, that wlhilst coryza and asthma are excited only by the dust of his shlop, lie in certain localities suffers at night from simple asthma without coryza.Sneezing may sometimes be indutced by v-iolent exercise.A patient, who has been a sneezer for twelve years, assures us that in his case this is the most powerful exciting cause, and lie always suffers severely if hlie takes a long ride on his bicycle.The sneez- ing generally lasts half an hour or more, and is accompanied by profuse watery nasal discharge.When the exercise takeii is uii- usually violent, the nose swells about thle bridge, and thle conjunctivw become red and irritable.lie does not suffer from itch- ing of the nose or any part of the face.The attacks are never excited by dust, and hlie is not affected in any way by smoke, hay, or the smell of flowers.lie has occasionally had an attack in tlhe middle of the nighlt, for which he can assign no cause.These night attacks, however, have ceased since he has worn a nigh1tcap.Two years ago he became the subject of peptic asthma, and more recently caughlt cold, which brought on an attack of hroncllitic asthma.The asthmatic attacks usually commence about two or three o'clock in the morning, and terminate withl a sharp paroxysm of sneezing.IIis father was asthmatic, but has outgrown it.Food is sometimes assigned as the exciting cause of attacks of sneezing.A nervous man subject to attacks of neuralgia stated
Feasibility and clinical utility of EUS guided biopsy of pancreatic cancer for next-generation genomic sequencing.
Authors: Stephan Dreyer, Nigel Jamieson, Lisa Evers, Marc Jones, Sancha Martin, Fraser Duthie, Liz Musgrove, Susie Cooke, Peter Bailey, Colin J McKay, David Kuang-Fu Chang, Andrew Biankin
Journal: Journal of Clinical Oncology (2017)

e15755 Background: Next-generation sequencing (NGS) has made genomic profiling to guide therapy a reality for many cancer types. The aim of this study is to investigate the feasibility of genomic profiling using standard clinical endoscopic ultrasound (EUS) core biopsy samples of Pancreatic Cancer (PC) to allow personalised cancer care. Methods:Patients undergoing EUS and biopsy for suspicion of PC underwent additional biopsies which was snap frozen. En-face frozen section enabled targeted macro-dissection prior to DNA extraction, quantification and targeted sequencing using a commercially available 151 gene ClearSeq Comprehensive Cancer Panel. Matching formalin-fixed (FFPE) diagnostic EUS biopsy and fresh frozen surgical resection specimens underwent genomic profiling for comparison. Whole genome sequencing (WGS) was performed in 2 patients. RNA sequencing was performed in samples with sufficient RNA yield. Results: Known PC genes ( KRAS, GNAS, TP53, CDKN2A, SMAD4) were identified in 27 out of 30 (90%) patients with histological diagnosis of PC. Potentially actionable somatic mutations (BRCA1, BRCA2, ATM, BRAF, JAK3) were found in 6 (20%) patients. In the 2 samples selected, WGS of the EUS samples confirmed point mutations identified on panel sequencing and revealed relevant mutational signatures and structural variation patterns. Targeted panel sequencing was successful in all FFPE samples. In 1 chemotherapy naïve patient, sequencing of a matching trio of fresh frozen and FFPE EUS biopsies, and resection sample revealed evidence of spatial intra-tumoral heterogeneity. In another patient, pre-treatment biopsy revealed a somatic BRCA1 mutation, and patient had a near complete pathological response to platinum containing neoadjuvant therapy in the resected specimen. RNA sequencing segregated patients into key clinically relevant molecular PC subtypes based on transcriptome as recently described. Conclusions: We demonstrate here novel multi-omic analysis of pancreatic cancer using standard clinical EUS guided fine needle biopsies. Multi-omic analysis of EUS biopsies offers potential clinical utility to guide personalized therapy of PC in the neoadjuvant and advanced settings.
Weather and Disease
Journal: JAMA (2019)

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
5α-reductase from radical prostatectomy tissue utilizes both testosterone and androstenedione to produce DHT: a dual isotope method and preliminary results.
Authors: Evan Kovac, Kai-Hsiung Chang, Eric A. Klein, Nima Sharifi
Journal: Journal of Clinical Oncology (2015)

e16018 Background: Previous work has shown that 5α-reductase prefers androstenedione (AD) in favor of testosterone (T) for dihydrotestosterone (DHT) synthesis in castration-resistant prostate cancer. Yet, 5α-reductase substrate preference in the setting of localized prostate tissue has yet to be fully elucidated. We propose a novel ex-vivo method for tracking steroid handling by the prostate and report our preliminary findings. Methods: Prostate tissue from the peripheral and transitional zones of patients who underwent radical prostatectomy (RP) for localized prostate cancer were incubated in media, along with (3H)-labeled AD and (14C)-labeled T. Media was collected after 7, 24 and 48 hours of incubation, treated with glucuronidaseand high performance liquid chromatography (HPLC) was used to identify steroids tagged with either 3H or 14C . Results: In total, 24 patients were consented for tissue procurement at the time of RP. Qualitatively, both AD and T are utilized by the prostate to produce DHT. Over time, concentrations of tritiated AD decreased over time, while concentrations of tritiated T, 5α-androstanedione and DHT rose. Similarly, concentrations of 14C-T decreased over a 48-hour period, while AD, 5α-androstanedione and DHT increased. Conclusions: We describe a dual isotope method for characterizing androgen handling by prostate tissue from patients with localized prostate cancer, using 2-channel radiolabel detection. Preliminary results show that both AD and T can be utilized by localized prostate tissue. Future work will focus on determining if different phenotypes of androgen handling exist among various patient genotypes and cancer risk types.
Season's Greetings
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1978)

The holiday season is a good time for reflection. Looking back over the year now drawing to a close, the Journal's first entirely under the current editorial management, what new trends can be perceived? In general, very few. We have continued to follow the course charted by our predecessors, maintaining a balance of content and a format designed to appeal to the broadest possible medical readership.Original scientific contributions, published under the headings of "Original Articles" and "Medical Intelligence," are still our primary stock in trade. Some 3000 unsolicited new manuscripts of this kind arrived on our editorial desk . . .
Abstract 5195: Efficacy of histone deacetylase inhibitors in a 3D cell culture model
Authors: Macarena Irigoyen, Gonzalo Castillo
Journal: Cancer Research (2019)

Abstract Epigenetic dysregulation, changes in gene expression not due to changes in the DNA sequence, is the underlying cause of many diseases including cancer. Identification of enzymatic chromatin-complex modulators that can restore chromatin homeostasis is critical to developing better therapeutic agents for both, hematologic and solid tumors. 3D cell culture models have been developed to overcome the limitations of monolayer in vitro assays, to include the complexity of the tumor microenvironment known to modulate epigenetic factors, such as cell-cell interaction and allowing for formations of metabolic gradients, factors known to play a role in epigenetic drug efficacy and resistance. In this study, we evaluated the efficacy of class I and II Inhibitors of histone deacetylases, SAHA and Trichostatin A, in a 3D cell culture in vitro assay across several human tumor carcinoma cell lines. The cell lines were grown in 3D cell cultures, and efficacy of the drugs was evaluated at 72 hours and ten days. All the cell lines grown as spheroids proved to be highly sensitive to SAHA and Trichostation A. AGS, a stomach adenocarcinoma cell line, showed the highest sensitivity to SAHA with an IC50 of 270 nM. Trichostatin A, on the other hand, displayed higher sensitivity to the ovarian carcinoma cell line, SKOV3, with an IC50 of 190 nM. In all cases, maximum potency was seen at the 10-day incubations with IC50s below 1 µM for all the cell lines in the panel. Drug-drug combinations with the epigenetic drugs were also studied, the results are discussed. Citation Format: Macarena Irigoyen, Gonzalo Castillo. Efficacy of histone deacetylase inhibitors in a 3D cell culture model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5195.
COUNCIL ON NATIONAL SECURITY
Journal: JAMA (1961)

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
Failing to address the burden of alcohol
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2020)

Excessive alcohol consumption is a leading cause of disease and premature mortality worldwide. Harmful alcohol use costs 3 million lives a year globally, is the seventh most important risk factor for mortality overall, and the number one risk factor for people aged 15–49 years. Excessive alcohol consumption increases the risk of a wide range of diseases, including cardiovascular diseases, liver disease, and cancers, and it can severely impact mental health and become a source of addiction. Despite the evident harms, it remains a major public health issue.
Uncomfortable truths
Authors: Graham Easton
Journal: BMJ (2005)

In neurons, local protein synthesis in synaptodendritic microdomains has been implicated in the growth and plasticity of synapses. Prerequisites for local translation are the targeted transport of RNAs to distal sites of synthesis in dendrites and translational control mechanisms to limit synthesis to times of demand. Here we identify dendritic BC1 RNA as a specific repressor of translation. Experimental use of internal ribosome entry mechanisms and sucrose density gradient centrifugation showed that BC1-mediated repression targets translation at the level of initiation. Specifically, BC1 RNA inhibited formation of the 48S preinitiation complex, i.e., recruitment of the small ribosomal subunit to the messenger RNA (mRNA). However, 48S complex formation that is independent of the eukaryotic initiation factor 4 (eIF4) family of initiation factors was found to be refractory to inhibition by BC1 RNA, a result that implicates at least one of these factors in the BC1 repression pathway. Biochemical experiments indicated a specific interaction of BC1 RNA with eIF4A, an RNA unwinding factor, and with poly(A)-binding protein. Both proteins were found enriched in synaptodendritic microdomains. Significantly, BC1-mediated repression was shown to be effective not only in cap-dependent translation initiation but also in eIF4-dependent internal initiation. The results suggest a functional role of BC1 RNA as a mediator of translational control in local protein synthesis in nerve cells.
Neglected Hip Fusion Surgery Renewed In Chicago Procedure
Journal: JAMA (1966)

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
Obituaries
Authors: Emanuel M. Steindler
Journal: JAMA (1989)

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
Howard W. 'Pete' Doan, MD, military, civilian leader, dies
Journal: JAMA (1980)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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