tbuckley/cabot-search huggingface dataset:
Hypoxia Induces Transcriptional and Translational Downregulation of the Type I IFN Pathway in Multiple Cancer Cell Types
Authors: Ana Miar, Esther Arnaiz, Esther Bridges, Shaunna Beedie, Adam P. Cribbs, Damien J. Downes, Robert A. Beagrie, Jan Rehwinkel, Adrian L. Harris
Journal: Cancer Research (2020)

Hypoxia is a common phenomenon in solid tumors and is strongly linked to hallmarks of cancer. Recent evidence has shown that hypoxia promotes local immune suppression. Type I IFN supports cytotoxic T lymphocytes by stimulating the maturation of dendritic cells and enhancing their capacity to process and present antigens. However, little is known about the relationship between hypoxia and the type I IFN pathway, which comprises the sensing of double-stranded RNA and DNA (dsRNA/dsDNA) followed by IFNα/β secretion and transcriptional activation of IFN-stimulated genes (ISG). In this study, we determined the effects of hypoxia on the type I IFN pathway in breast cancer and the mechanisms involved. In cancer cell lines and xenograft models, mRNA and protein expressions of the type I IFN pathway were downregulated under hypoxic conditions. This pathway was suppressed at each level of signaling, from the dsRNA sensors RIG-I and MDA5, the adaptor MAVS, transcription factors IRF3, IRF7, and STAT1, and several ISG including RIG-I, IRF7, STAT1, and ADAR-p150. Importantly, IFN secretion was reduced under hypoxic conditions. HIF1α- and HIF2α-mediated regulation of gene expression did not explain most of the effects. However, ATAC-seq data revealed in hypoxia that peaks with STAT1 and IRF3 motifs had decreased accessibility. Collectively, these results indicate that hypoxia leads to an overall downregulation of the type I IFN pathway due to repressed transcription and lower chromatin accessibility in an HIF1/2α-independent manner, which could contribute to immunosuppression in hypoxic tumors. SIGNIFICANCE: These findings characterize a new mechanism of immunosuppression by hypoxia via downregulation of the type I IFN pathway and its autocrine/paracrine effects on tumor growth.
Influence of Hyaluronan Density on the Behavior of Breast Cancer Cells with Different CD44 Expression (Adv. Healthcare Mater. 4/2022)
Authors: Ana M. Carvalho, Diana Soares da Costa, Rui L. Reis, Iva Pashkuleva
Journal: Advanced Healthcare Materials (2022)

Medical Applications of Glycomaterials In article number 2101309 by Iva Pashkuleva and co-workers, featured in this issue's Medical Applications of Glycomaterials Special Section, hyaluronan gradients are developed by a two-step procedure: i) diffusional deposition of colloidal nanoparticles to obtain a gradient of gold nanoparticles and ii) immobilization of end-on-thiolated hyaluronan on this gradient. These gradients allow high-throughput screening of cells. While CD44 negative cells do not change along the gradient, the response of CD44 positive cells depend on the level of CD44 expression and hyaluronan density.
Risk taking.
Authors: D. Black
Journal: BMJ (1989)

by patients in the correspondence on this topic sent to the British Diabetic Association is that doctors may refuse to acknowledge that a particular patient is having continued problems with human insulin despite adjustments in dose.In some cases changing back to the insulin species with which the diabetes was previously stabilised-either porcine or bovine-has been shown to restore warning symptoms of hypoglycaemia.30Doctors should, therefore, be aware of the risk of altered control, explain this risk to their patients (as well as the reasons for any changeover), and closely monitor the patient in the subsequent weeks.It is particularly necessary to warn patients of the danger of hypoglycaemia while driving and remind them of the need for checking blood glucose concentrations before the journey and at about two hourly intervals during long periods of driving.Doctors should take any adverse effects seriously and even be ready to
Abstract 331: Argon Promotes Vasorelaxation in Rat Pulmonary and Mesenteric Arteries
Authors: Elaine L Shelton, Courtney D Berger, Michele M Salzman, Claudius Balzer, Matthias L Riess
Journal: Circulation (2018)

Introduction: Despite cardiopulmonary resuscitation (CPR), more than 90% of patients having an out-of-hospital cardiac arrest in the US still die or endure severe neurological damage due to ischemia/reperfusion (IR) injury. Ventilation with Argon during CPR improves oxygenation, cardiac output, and survival in a porcine model of cardiac arrest. Similarly, inhalation of the volatile anesthetic, Sevoflurane, during CPR improves hemodynamic outcomes, but its usefulness is limited by its anesthetic effect and potential harm to providers and bystanders. In contrast, non-anesthetic noble gases like Argon can be safely administered outside of the hospital and may serve as a feasible adjuvant to mitigate IR injury following cardiac arrest. We hypothesize that Argon can decrease pulmonary and/or systemic vascular resistance, which may improve hemodynamic outcomes. Methods: Pressure myography assays were performed on isolated rat pulmonary and mesenteric arteries to determine the ability of Argon to promote vasodilation. Vessels were mounted in microvessel perfusion chambers and challenged with oxygenated Krebs buffer balanced with Argon (65%Argon:30%O 2 :5%CO 2 ) or Nitrogen (65%N 2 :30%O 2 :5%CO 2 ). Changes in intra-luminal diameter were recorded. Statistics: one-way ANOVA, p&lt; 0.05. Results: Pulmonary arteries dilated in response to O 2 , while mesenteric arteries constricted. Argon exposure made pulmonary vessels significantly more sensitive to O 2 -induced dilation (mean Argon dilation = 133%, mean N 2 dilation = 99%). Conversely, argon blunted the ability of O 2 to constrict mesenteric arteries (argon mean constriction = 35%, nitrogen mean constriction = 41%). Conclusion: Our results indicate that Argon has vasodilatory effects in both the pulmonary and systemic circulations, making it a potentially useful therapeutic tool for mitigating IR injury following cardiac arrest or other instances of prolonged hypoperfusion. Future studies will address the mechanism underlying the ability of an inert noble gas to affect vasoactive signaling pathways.
RU-486
Authors: Raymond J. Godefroid
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Dr Baulieu surely is deserving of the Albert Lasker Medical Award for his extensive research work on progesterone receptors; however, allowing this gifted researcher the opportunity to try to justify his position on the ethical merits of chemical abortion is ludicrous.<sup>1</sup> Calling the abortion produced by RU-486 "contragestion" does not diminish the fact that a developing human being is being sloughed unnaturally from the uterus. Changing terminology cannot change the facts. The term "fertility control" used by Dr Baulieu is not control, but destruction. Not allowing fertilization to occur illustrates control, but the overt blocking of a natural hormone to bring about miscarriage... that's abortion! Aside from the abortion controversy, the therapeutic merits of RU-486 are dubious at best. A drug that fails when given alone more than 20% of the time and when administered with a prostaglandin pessary that still has a failure rate of
AMERICAN COLLEGE OF PHYSICIANS
Authors: S. MARX WHITE
Journal: Annals of Internal Medicine (1931)

Editorial1 May 1931AMERICAN COLLEGE OF PHYSICIANSS. MARX WHITE, B.S., M.D.S. MARX WHITE, B.S., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-11-1478 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptBorn, 1873; B.S., University of Illinois; M.D., Northwestern University Medical School, 1897; Postgraduate work at the University of Vienna and the University College Hospital of London; Demonstrator, Pathology and Bacteriology, University of Minnesota Medical School, 1898-00; Assistant Professor of Medicine at same institution, 1900-08; Associate Professor of Medicine at same institution, 1908-19; Professor of Medicine at same institution, 1900 to date; Member of Staff, Northwestern Hospital, 1908 to date, St. Mary's Hospital, 1919 to date, Abbott Hospital, 1921 to date; Eitel Hospital, 1926 to date; Member and ex-President of the Minnesota State Board of Health; Member, Nu Sigma Nu, Alpha... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Minneapolis, Minnesota PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1931Volume 4, Issue 11Page: 1478-1479KeywordsBacteriologyHospital medicine ePublished: 1 December 2008 Issue Published: 1 May 1931 PDF downloadLoading ...
Abstract 17308: Effect of HIV Protein-Tat &amp; Cocaine on Hippo-YAP Signaling Axis in Pulmonary Arterial Smooth Muscle Cells
Authors: Aradhana Mohan, Himanshu Sharma, Mahendran Chinnappan, Navneet K Dhillon
Journal: Circulation (2018)

Introduction and hypothesis: Intravenous drug use (IVDU) is considered to be one of the important risk factors in the development of HIV-associated pulmonary arterial hypertension (HPAH). Our previous findings demonstrate that the exposure of cocaine to HIV infected individuals has an additive effect in enhancing the proliferation of pulmonary smooth muscle cells, thus further amplifying the development of pulmonary arteriopathy. Furthermore, various studies suggest the failure of Hippo pathway and increased YAP/TAZ activity in pulmonary hypertension (PH). Based on this, we hypothesized that YAP axis might be having a role in HIV and cocaine mediated smooth muscle hyperplasia. Methods: Primary human pulmonary arterial smooth muscle cells (HPASMCs) were grown and treated with cocaine hydrochloride (1μM) and/or HIV-Tat protein (25ng/mL) for 6h. In addition, primary HPASMC were treated for 24h with extracellular vesicles (EVs) transfected with miR-130a antagomir or scrambled miR followed by treatment of EVs isolated from supernatants of monocyte derived macrophage infected with HIV-Bal (5ng/ml) in the presence or absence of cocaine for 4 days. The expression of Hippo proteins was determined using western blot. Results: Combined treatment of HPASMCs with HIV-Tat and cocaine for 6h showed no change in the expression of MST proteins, however reduced expression of phosphorylated LATS1 relative to total LATS1 was observed. This correlated with the decline in the phosphorylated YAP to total YAP ratio. Pre-treatment of HPASMCs with YAP/TAZ inhibitor attenuated the HIV-Tat and cocaine mediated augmentation of cell proliferation. Furthermore, our recent findings demonstrate that EVs derived from HIV infected and cocaine treated MDMs (H+C EVs) when added to HPASMC result in increased proliferation on transfer of miR-130a. We now found that this H+C EVs mediated hyper-proliferation of smooth muscle cells is associated with the increased levels of total YAP protein. In addition, H+C EVs mediated increase in total YAP was prevented on the pretreatment of HPASMCs with EVs carrying anti-miR-130a. Conclusion: In conclusion, our preliminary findings suggest increased activation of Hippo-YAP signaling in pulmonary smooth muscle cells on the direct treatment with HIV protein and cocaine and also on exposure to EVs derived from HIV infected and cocaine treated macrophages.
Abstract 279: Cardiac Arrest is Associated With a Global Level Alteration in Oxygen Metabolism: A Clinical Pilot Study
Authors: Koichiro Shinozaki, Kota Saeki, Qiuping Zhou, Hugh Cassiere, Lee Jacobson, Daniel Rolston, Julianne Falotico, Timmy Li, Marc Olshan, Matthew Levitus, Joshua W Lampe, Lance B Becker
Journal: Circulation (2018)

Objective: We recently reported that a global-level metabolic alteration occurs after cardiac arrest (CA) in our high fidelity rodent model. The finding was that dissociation of O 2 consumption (VO 2 ) and carbon dioxide generation (VCO 2 ) resulted in a respiratory quotient (RQ: calculated by dividing VCO 2 by VO 2 ) that fell well outside the normally cited range of 0.7-1.0. We hypothesized that a lowered RQ is similarly found in human CA patients. Methods: The study consisted of three subject groups: 1) healthy volunteer, 2) post-surgical patient (control) and 3) post-CA patient. We measured the VO 2 and VCO 2 of mechanically ventilated subjects using the Douglas bag method. Inspiration and expiration gas samples were collected in two separate bags . and RQ was calculated from CO 2 and O 2 gas concentrations in the samples. The patients and healthy volunteers were ventilated using the same model mechanical ventilator. Alert healthy volunteers bit onto a mouthpiece and the samples were collected, while post-surgical and post-CA patients were unconscious during the measurements. We measured the RQ of healthy volunteers at normal and high fractions of inspired oxygen (FIO 2 ) in order to test the validity of our methods at various inspired O 2 levels. Results: The RQs of the three healthy volunteers were 0.83, 0.92 and 0.85 at an FIO 2 of 0.21 and 0.86, 0.88, and 0.83 at an FIO 2 of 0.90 respectively. The RQs of the two post-surgical patients were 0.92 and 0.88 at an FIO 2 of 0.5. None of the post-surgical patients had any complications following the surgery and all were discharged. The RQ of a post-CA patient measured 2.5 hours after the CA was found to be 0.72 at an FIO 2 of 0.9. The CA patient expired within 24 hours of hospital admission. Conclusions: The same trend between the findings of both our rodent study and the CA patient suggest that resuscitation from CA alters cellular metabolism on a global level. This metabolic alteration in turn causes the dissociation of O 2 consumption and CO 2 generation resulting in a lowered RQ. Our findings warrant a larger clinical study to confirm a lowered RQ in post-CA patients and bench work to elucidate the causative mechanism of this relationship.
Rickettsial endocarditis.
Authors: W. P. Turck, M. B. Matthews
Journal: BMJ (1969)

Management of Acute SalicylatePoisoning SIR,-Unexpected sudden death has been a recognized feature of acute salicylate poisoning, and it still occurs.An early acidosis is the cause.Would not a blood pH done in casualty probably be life-saving ?The result can be obtained in 15 minutes- far quicker than the plasma-salicylate level.-I am, etc., Guy's Hospital, London S.El.R. C. MAC KEITH.Unusual Mycoplasma pneumoniae SIR,-We wish to report a case of Myco- plasma pneumoniae infection with an unusual presentation.The patient was a 5-year-old boy who five days before admission developed a maculo- papular, mildly pruritic erythematous rash.The rash appeared first on his upper arms and legs, and over the next three days spread up his trunk to involve the face.He was pyrexial during this time and had commenced a course of penicillin at home after the onset of the rash.He also had a mild irritant cough.There was no known contact with infectious or other disease.He had had rubella and chicken-pox and had been vaccinated against measles one year previously.No drugs had been taken prior to onset of the rash.A budgerigar was the only pet in close contact with the child.On examination his temperature was 100.4'F.
FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies
Authors: V. Subbiah, N.O. Iannotti, M. Gutierrez, D.C. Smith, L. Féliz, C.F. Lihou, C. Tian, I.M. Silverman, T. Ji, M. Saleh
Journal: Annals of Oncology (2022)

The phase I/II FIGHT-101 study (NCT02393248) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of pemigatinib, a potent and selective fibroblast growth factor receptor (FGFR) 1-3 inhibitor, as monotherapy or in combination therapy, for refractory advanced malignancies, with and without fibroblast growth factor (FGF) and receptor (FGFR) gene alterations.Eligible, molecularly unselected patients with advanced malignancies were included in part 1 (dose escalation; 3 + 3 design) to determine the maximum tolerated dose. Part 2 (dose expansion) evaluated the recommended phase II dose in tumors with or where FGF/FGFR activity is relevant.Patients (N = 128) received pemigatinib 1-20 mg once daily intermittently (2 weeks on/1 week off; n = 70) or continuously (n = 58). No dose-limiting toxicities were reported. Doses ≥4 mg were pharmacologically active (maximum tolerated dose not reached; recommended phase II dose 13.5 mg once daily). The most common treatment-emergent adverse event (TEAE) was hyperphosphatemia (75.0%; grade ≥3, 2.3%); the most common grade ≥3 TEAE was fatigue (10.2%). Dose interruption, dose reduction, and TEAE-related treatment discontinuation occurred in 66 (51.6%), 14 (10.9%), and 13 (10.2%) patients, respectively. Overall, 12 partial responses were achieved, most commonly in cholangiocarcinoma (n = 5) as well as in a broad spectrum of tumors including head and neck, pancreatic, gallbladder, uterine, urothelial carcinoma, recurrent pilocytic astrocytoma, and non-small-cell lung cancer (each n = 1); median duration of response was 7.3 months [95% confidence interval (CI) 3.3-14.5 months]. Overall response rate was highest for patients with FGFR fusions/rearrangements [n = 5; 25.0% (95% CI 8.7% to 49.1%)], followed by those with FGFR mutations [n = 3; 23.1% (95% CI 5.0% to 53.8%)].Pemigatinib was associated with a manageable safety profile and pharmacodynamic and clinical activity, with responses seen across tumors and driven by FGFR fusions/rearrangements and mutations. These results prompted a registrational study in cholangiocarcinoma and phase II/III trials in multiple tumor types demonstrating the benefit of precision therapy, even in early phase trials.
Abstract 17382: Jumonji-C Histone Demethylases Are Cellular Iron Sensors That Control mTORC1 and Mitophagy
Authors: Jason S Shapiro, Hsiang-Chun Chang, Hossein Ardehali
Journal: Circulation (2018)

Iron is an essential nutrient and is critical for cellular growth and metabolism. Here, we delineate a novel mechanism by which iron alters amino acid homeostasis and mTOR activity by remodeling the cellular epigenetic landscape. We find that iron deficiency inactivates Jumonji-C domain containing histone-demethylases, resulting in histone hyper-methylation and silencing of the leucine transporter LAT3 and obligatory mTORC1 cofactor RAPTOR. Additionally, we identify that mTOR-mediated regulation of RNA stability through tristetraprolin (TTP) is a novel and requisite step in selective-autophagy. In the absence of TTP, mitochondria damaged by the loss of iron cannot undergo fission, rendering the mitochondria too large for engulfment and subsequent recycling. Accumulation of damaged mitochondria leads to defective oxidative metabolism and impairs hepatic gluconeogenesis in response to fasting. These studies uncover a novel pathway that integrates iron sensing with cellular metabolism, mitochondrial dynamics and autophagy.
Abstract 17394: Hypertension in Adults: Quality Improvement Intervention Evaluation of a Self-Measured Blood Pressure Monitoring Program
Authors: Angelica M Smith, Holly A Buchanan, John W Lewis, Shelly P Smith
Journal: Circulation (2018)

Introduction: Hypertension (HTN) is an insidious condition that affects many Americans. This quality improvement initiative evaluated the effectiveness of HTN management through a Self-Measured Blood Pressure (SMBP) monitoring tool through Check.Change.Control® (CCC). Hypothesis: To implement CCC and evaluate the impact on blood pressure throughout rural primary care clinics and wellness clinics over a six month period. This initiative assessed barriers for patients to adhere to medication regimen and barriers for providers to engage in patients’ HTN management. Methods: This initiative used CCC data to evaluate blood pressure changes and trends. Survey monkey were used to assess and evaluate patients and providers barriers for HTN management. Results: The sample included 208 adults with diagnosis of HTN with medication regimen. Regular tool use resulted in 76% reporting BP equal or less than 140/90. Compliance with medication regimens improved to 79.23%. The overall mean reduction in systolic was -11.3 mm Hg and diastolic was –9.7 mm Hg. Barriers reported through surveys included forgetting to take medication (5%) and forgetting to pick up medication from the pharmacy (2%). Most survey respondents (89.97%) agreed that text message reminders helped them be compliant.Thirty-six percent of providers and clinical staff cited time as a limiting factor for enrolling patients; providers reported one third of patients (33%) cited lack of interest in the program as the barrier for enrollment. 87.67% of respondents asserted CCC was helpful in managing hypertensive patients and foresee continuing using the tool. Conclusions: This quality improvement initiative showed how the addition of CCC can aid improve compliance with medication regimens and blood pressure management. Technology empowered patients to better manage their HTN. High acceptance of the tool among providers, volunteers, and participants facilitated the connection between community, work, and healthcare organizations to improve HTN management. Future efforts should focus on creating and implementing initiatives to help reduce barriers for HTN management.
Lehrbuch der speziellen Chirurgie für Studierende und Aerzte.
Journal: JAMA (1927)

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
Intramuscular injections.
Authors: A. G. Butters
Journal: BMJ (1968)

JouB<rm 367 susceptibility to thromboembolism seems likely to be established within the first few months.Obviously it is important to know if there is a critical period of a few months (for argument's sake, between 24 and 36 weeks after commencement, corresponding to the critical period during pregnancy) after which the incidence of thromboembolism falls abruptly, or if the risk remains at the same level throughout the period of taking the pill (full allowance being made for agedependency).In other words, if the 10 cases of thromboembolism occurring within 6 months of starting the pill are disregarded, do the remaining 16 cases constitute a significantly high incidence of the disease ?Drs.Vessey and Doll's comments on this point would, I feel sure, be welcomed.-I am, etc.,