tbuckley/cabot-search huggingface dataset:
Abstract 20168: Enhanced Endothelial Nitric Oxide Production and Cardiac Dysfunction in an Inducible Endothelial-Specific miR-130a Mouse Model
Authors: Cynthia Harmon, Stefan Mazurek, Gene Kim
Journal: Circulation (2015)

Introduction: MicroRNA-130a (miR130a) has been shown to be important in cardiovascular gene regulation in both normal and diseased states. We recently reported on the regulation of connexin43 by miR130a. Methods: We created an inducible mouse model to express miR-130a in endothelial cells under the control of the VE-cadherein promoter (VE-cad-miR130a). Overexpression of miR-130a was initiated in adult mice at weaning, approximately 4 weeks post-birth. Results: Survival analysis revealed &gt;50% mortality by 9 weeks of age with overexpression of miR-130a. By 9 weeks of age, LV function was reduced (26.4% ± 4 vs 33.6% ± 6 in controls, p&lt;0.001, n=10). Prior to the onset of LV dysfunction; we found numerous abnormalities in cardiac function. First, we noted significant bradycardia on ambulatory telemetric recordings (389bpm ± 90 vs 534bpm ± 72 in controls, p&lt;0.0001, n=3). Moreover, the cardiac response to β-AR stimulation was blunted in VE-Cad-miR130a mice relative to control when challenged with isoproterenol. Interestingly, sinus node recovery time was significantly prolonged, supportive of sinus node dysfunction. While predominately in sinus rhythm, we found episodes of spontaneous atrial tachyarrhythmias, which were confirmed on invasive electrophysiologic testing. To investigate further, we performed patch clamp measurements of action potential duration (APD) in atrial cariomyocytes. APD was significantly prolonged in VE-Cad-miR130a myocytes (APD90 325ms vs 60ms, p&lt;0.00001, n=3). Next, we performed invasive blood measure measurements and found a significant decrease in mean arterial blood pressure (76.9mmHg ± 3 vs 94.3mmHg ± 5 in controls, p&lt;0.01, n=4). Based on previous reports of increased nitric oxide in the setting of loss of endothelial connexin43, we found significant elevation of NO concentration in VE-Cad-miR130a. Inhibition of NO synthase via IP administration of L-NAME increased MAP in VE-Cad-miR130a to a maximum steady-state mimicking that of control mice. Conclusions: Overexpression of miR-130a in endothelial cells promotes impaired cardiovascular function and abnormal atrial conduction. These results suggest a newly identified role for endothelial miR-130a in the development of hypotension and cardiac dysrhythmias.
Transient global amnesia
Authors: R. M. Kennedy
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Because of recent experience with a patient with transient global amnesia (TGA), we, too, have been reviewing our medical records of patients with this disorder, as did Nausieda and Sherman (241:392, 1979). One of our patients is a previously healthy 52-year-old right-handed man who has had one episode of a stereotypical attack of TGA.<sup>1</sup>Findings from his neurological examination were normal shortly after the episode. Results of laboratory tests, including computerized tomographic head scan, were normal except for two EEGs, which were severely abnormal, showing active single left temporal spike discharge with paroxysmal generalized delta slowing. In reviewing the records of seven other patients with TGA, we found two others with similar EEG findings—one in whom major motor seizures developed. These findings focused us toward the concept that TGA may be on occasion an epileptogenic phenomena rather than a vascular one, per se. For our patient,
Heart Disease in Early Life.
Journal: JAMA (1930)

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
Comparative analysis of survival in colon cancer undergoing sentinel lymph node mapping vs conventional surgery based on number of positive lymph nodes.
Authors: Sabarina Ramanathan, Sukamal Saha, Suresh Mukkamala, Michael Hicks, Patrick Knight, Vinay Bajaj, Daniel Mazzaferro, Thushy Siva, Lori Hutcherson, David Livert, Rajen Oza, David Wiese, Madan L. Arora
Journal: Journal of Clinical Oncology (2017)

e15154 Background: Unlike in breast cancer or melanoma, resection during sentinel lymph node mapping (SLNM) in colon cancer (CCa) includes regional lymphadenectomy including SLNs and non-SLNs. However, SLNM often identifies micrometastases that can be missed by conventional (Conv) surgery and pathologic examination. It is unknown whether this impacts survival or recurrence. Hence, a retrospective analysis was undertaken to study overall (OS) and disease -specific (DSS) survival between patients (pts) undergoing SLNM vs Conv surgery based on the number of +ve LNs. Methods: SLNM was done by subserosal injection with blue dye followed by segmental resection including regional lymphadenectomy. All SLNs were ultrastaged and other nodes were examined by conv. methods with H&amp;E. Results: There were 309 pts in SLNM (GpA) vs 499 pts in Conv surgery (GpB); with average no. of lymph nodes (LNs) and +ve LNs 17.3/1.6 vs 14.4/2.49 respectively. For GpA, success rate was 99.6% and the average no of SLN was 3. Of the pts in GpA vs GpB, 1+ve LN were found in 38% vs 27%, 2+ve LNs in 10% vs 16%, and &gt; 2 LNs in 53% vs 57%, respectively. Comparing 5 years OS between GpA vs GpB, for 1+ve LN was 62.8% vs 52.38%, for 2 +ve LNs 72.7% vs 48.65% and for &gt; 2 +ve LNs 35% vs 33.33%, respectively. Similarly, DSS for 1 +veLN was 54.4% vs 47.6%, 2+ve LNs 40% vs 40.54% and &gt; 2+ve LNs, 30.4% vs 25.76%, respectively (Table). Conclusions: Compared to Conv surgery, SLNM identified higher no. of LNs per pt with high success rate. Five-year OS and DSS also are better in SLNM vs Conv surgery for all +ve LN gps. Hence, SLNM in CCa may have prognostic value. A larger multicenter trial needs to be done to validate such data. [Table: see text]
Value of Radiation Therapy in Leiomyosarcoma of Uterus
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
Mutant (MT) <i>KRAS</i> codon 12 and 13 alleles in patients (pts) with metastatic colorectal cancer (mCRC): Assessment as prognostic and predictive biomarkers of response to panitumumab (pmab).
Authors: Marc Peeters, Jean-Yves Douillard, Eric Van Cutsem, Salvatore Siena, Kathy Zhang, Richard Thomas Williams, Jeffrey S. Wiezorek
Journal: Journal of Clinical Oncology (2012)

3581 Background: Pmab is a fully human monoclonal antibody against the epidermal growth factor receptor (EGFR). Significant improvement in progression-free survival (PFS) was demonstrated in pts with wild-type (WT) KRAS mCRC treated with pmab+FOLFOX4 (1 st -line; study 20050203), pmab+FOLFIRI (2 nd -line; study 20050181), and pmab monotherapy (study 20020408). In mCRC, mutations in KRAS codons 12 and 13 are established biomarkers for lack of clinical benefit to anti-EGFR therapies. We retrospectively examined individual MT KRAS codon 12 and 13 alleles as prognostic and predictive biomarkers of response in three phase 3 studies. Methods: Pts were randomized to receive FOLFOX4, FOLFIRI, or best supportive care +/- pmab 6.0 mg/kg Q2W in trials 20050203, 20050181, and 20020408, respectively. The MT KRAS codon 12 and 13 alleles (G12A, G12C, G12D, G12R, G12S, G12V, G13D) were detected using the Therascreen K-RAS Mutation Kit (Qiagen). Results: MT KRAS codon 12 and 13 alleles were detected in 40% (440/1096), 45% (486/1083), and 43% (184/427) of pts in trials 20050203, 20050181, and 20020408, respectively. MT KRAS allele distribution was conserved across studies and balanced between treatment arms. Baseline demographic and clinical features were comparable between all MT KRAS allele subgroups. There was no consistent evidence that any individual MT KRAS allele, compared to the remaining MT KRAS alleles or the entire MT KRAS group, differentially impacted PFS or overall survival (OS) in control arm-treated or pmab-treated pts. Only in the pmab+FOLFOX4 arm of study 20050203 were G13D (unfavorably) and G12V (favorably) significantly associated with OS. Response rates were similar between MT KRAS allele groups in the 1 st - and 2 nd -line mCRC treatment setting. Finally, in analyses of pts pooled from all 3 trials, only the G12A KRAS allele emerged as a significant negative predictive factor for OS. Conclusions: The lack of consistent results across three lines of therapy indicates pts whose tumors harbor MT KRAS codon 12 or 13 alleles are unlikely to respond to pmab therapy. Currently, only pts with WT KRAS mCRC should be treated with EGFR antibodies.
Abstract 2103: NETs promote tumor resistance to anthracyclines
Authors: Cindy Lin, Sarah E. Herlihy, Marina Li, Hui Deng, Luca Bernabei, Dmitry I. Gabrilovich, Dan T. Vogl, Yulia Nefedova
Journal: Cancer Research (2019)

Abstract Multiple Myeloma (MM) is an incurable blood cancer characterized by the clonal proliferation of plasma cells that accumulate in the bone marrow (BM). Resistance to chemotherapy represents one of the main challenges in the treatment of this disease. We have previously shown that neutrophils, one of the major cellular populations in the BM, protect MM cells from chemotherapies including anthracyclines; however, the mechanisms of this effect remain unknown. Thus, we set out to investigate the mechanisms by which neutrophils reduce sensitivity of tumor cells to anthracyclines. Neutrophil extracellular traps (NETs) are structures composed of chromatin and protein formed by neutrophils that are a part of an innate immune mechanism of binding and killing pathogens. Recently, NETs have been shown to form in cancer patients as well as tumor-bearing animals and have been implicated in solid tumor progression; however, their role in hematological malignancies remain poorly understood. Utilizing an in vitro culture system, we demonstrated that MM cells were able to induce NET formation by BM neutrophils. Interestingly, neutrophils isolated from the BM of patients with MM have a significantly higher ability to produce NETs in response to tumor cells as compared to BM neutrophils from donors. NET formation was accompanied by an increase in the level of extracellular DNA. Using imaging flow cytometry and confocal microscopy we demonstrated that extracellular DNA is internalized by tumor cells and localizes to the cytoplasm. This internalized DNA was able to bind to doxorubicin and other anthracyclines thereby reducing their cytotoxic effects. Significantly increased cell-free DNA levels were detected in BM aspirates from MM patients as well as in tumor-bearing mice. Targeting the extracellular DNA in vivo using the clinically available DNase, Pulmozyme, restored the sensitivity of tumor cells to doxorubicin resulting in prolonged survival of tumor-bearing animals. Here, we have identified a novel mechanism of resistance to anthracyclines that is mediated by neutrophils in the tumor microenvironment and provided evidence to support the premise that targeting this mechanism would be of significant benefit in the treatment of MM. Citation Format: Cindy Lin, Sarah E. Herlihy, Marina Li, Hui Deng, Luca Bernabei, Dmitry I. Gabrilovich, Dan T. Vogl, Yulia Nefedova. NETs promote tumor resistance to anthracyclines [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 2103.
Radiation Dosimetry
Authors: John Cameron
Journal: Environmental Health Perspectives (1991)

This article summarizes the basic facts about the measurement of ionizing radiation, usually referred to as radiation dosimetry. The article defines the common radiation quantities and units; gives typical levels of natural radiation and medical exposures; and describes the most important biological effects of radiation and the methods used to measure radiation. Finally, a proposal is made for a new radiation risk unit to make radiation risks more understandable to nonspecialists.
Drug Therapy
Authors: R. J. Main
Journal: JAMA (1962)

This pocket-sized book stresses the author's opinions and recommendations on the clinical use of modern drugs; the drugs are classed under functional headings, preceded by a brief general, critical discussion of the pharmacology and choice of drug of each class. Adverse effects, dosage forms, and trade names are clearly given. The inclusion of vaccines and plasma is very helpful, since most pharmacology texts do not admit that such are drugs. Because this is a small book, the drugs tend to be classed as either white or black, since there is no room to discuss comparative shades of gray. The author leaves no doubt of his opinion of drugs, even at the expense of grammar, as when he states that one drug "is no good." However, several published studies indicate that not all clinicians agree with this specific judgment, nor would they with the statement that a certain antibiotic responsible for
The accidental tourist: medical emergencies in the air
Authors: B. B. Dan
Journal: JAMA (1989)

Each year 550 million air travelers pass through the 25 busiest airports in the United States.<sup>1</sup>More people enplane, deplane, and transfer through Chicago's O'Hare International Airport annually than live in Australia, New Zealand, Sweden, Finland, Norway, Denmark, Switzerland, Ireland, Greece, and the Congo combined. With such large congregations of people in unusual conditions, both in the air and on the ground, one might expect some unusual occurrences of medical emergencies. In this issue ofThe Journal, Cummins and Schubach<sup>2</sup>report on their survey of emergency medical responses at one large air terminal, the Seattle-Tacoma International Airport. In the 1-year prospective study, they found that the frequency of emergency calls was relatively low, approximately 1 per 20 000 traveling passengers. This incidence is probably similar to or smaller than what is seen at a football game, rock concert, or any other large gathering of reasonably healthy people. Interestingly,
SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine and Ovarian Carcinosarcoma with HER2/Neu Expression
Authors: Gulden Menderes, Elena Bonazzoli, Stefania Bellone, Jonathan Black, Federica Predolini, Francesca Pettinella, Alice Masserdotti, Luca Zammataro, Gary Altwerger, Natalia Buza, Pei Hui, Serena Wong, Babak Litkouhi, Elena Ratner, Dan-Arin Silasi, Masoud Azodi, Peter E. Schwartz, Alessandro D. Santin
Journal: Clinical Cancer Research (2017)

Purpose: Carcinosarcomas (CS) are highly aggressive gynecologic malignancies containing both carcinomatous and sarcomatous elements with heterogeneous HER2/neu expression. We compared the efficacy of SYD985 (Synthon Biopharmaceuticals BV), a novel HER2-targeting antibody-drug conjugate (ADC), to trastuzumab emtansine (T-DM1, Genentech-Roche) against primary uterine and ovarian CS.Experimental Design: Eight primary CS cell lines were evaluated for HER2/neu surface expression by IHC and gene amplification by FISH assays. The in vitro experiments included cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), proliferation, viability, and bystander killing. In vivo activity was studied in mouse xenograft and patient-derived xenograft (PDX) models.Results: SYD985 and T-DM1 induced similar levels of ADCC against CS cell lines with low and high HER2/neu expression when challanged in the presence of effector cells. In contrast, SYD985 was 7- to 54-fold more potent than T-DM1 in the absence of effector cells. SYD985, unlike T-DM1, was active against CS demonstrating low or heterogeneous HER2/neu expression. Specifically, the mean IC50 values were 0.060 μg/mL and 3.221 μg/mL (P < 0.0001) against HER2/neu 0/1+ cell lines and 0.013 μg/mL and 0.096 μg/mL (P < 0.0001) against HER2/neu 3+ cell lines for SYD985 versus T-DM1, respectively. Importantly, unlike T-DM1, SYD985 induced efficient bystander killing of HER2/neu 0/1+ tumor cells admixed with HER2/neu 3+ cells. In vivo studies confirmed that SYD985 is more active than T-DM1 in CS and highly effective against HER2/neu expressing xenografts and PDX.Conclusions: SYD985 may represent a novel and highly effective ADC against HER2-expressing CS. Clinical studies with SYD985 in patients harboring chemotherapy-resistant CS with low/moderate and high HER2 expression are warranted. Clin Cancer Res; 23(19); 5836-45. ©2017 AACR.
Endoscopy and oesophagus
Authors: Enteropathy Am, P Kelly1, Jom Pobee2, I Segal3, S Spies4, Transmitter Swain, F Gong, T Mills, J Yiannakou, Colette Hawkins, C Garvey, A Morris, Bell Gd, Williams Cb
Journal: Gut (1996)

Introduction and aims Tropical enterathy has boen de-cribd in the healthy indigenous populations of several African countries.The mechanisms underlying the small intestinal mucosal changes in this syndrome remain unclear.T cell activation has been demonstrated to result in villous atrophy and crypt hyperplasia, and we therefore investigated whether this process has a role in the pathogenesis of tropical enteropathy.Patients and methods 10 black Zambian subjects, 20 black South African subjects, and 22 white South African subjects undergoing routine upper GI endoscopy for dyspepsia (GU, DU, diarr and AIDS excluded) were studied.Distal duodenal villous height (VH) and crypt depth (CD) was measured by computeised image analysis of formalin-fixed paraffin-processed biopsies.Snap-frozen duodenal biopsies were subjected to dual colour immunofluorescence staining for CD69/CD3, allowing quantitative assessment of T cell expression of the activation marker CD69.Results Median VH was lower [308 vs 412 (235- 456)gm p<0.05], and CD greater [190 (141-206) vs 154 (119-188) p<0.05], in Zambians compared to black South Africans. Thee wasno significant difference in VH or CD between black and white South Africans. Median percentage CD69/CD3 was greater in Zambians compared to black South Africans [80 vs 60.3 (33-86) p<O.001] but white South African CD69 expression [66.5 (35-95.5)] was not signiicantly different from that of black South Africans.Conclusions Tropical enteropathy is present in the black Zambian population but not in the relatively less deprived urban black South African population.Tropical enteropathy is associated with small intestinal mucosal T cell activation.
Preoperative Prediction of Postoperative Delirium
Authors: Richard C. Carson
Journal: JAMA (1994)

<h3>To the Editor.</h3> —I wish to thank you for publishing "A Clinical Prediction Rule for Delirium After Elective Noncardiac Surgery" by Dr Marcantonio and colleagues.<sup>1</sup> No doubt you will receive correspondence criticizing the research for not including an anesthesiologist among the 14 authors of this article. Others may also be critical of the exclusion of any references from the anesthesiology literature in this study in which all of the 1341 patients studied had received anesthesia. However, I personally am grateful for this article. Since I can now identify the "appropriate candidates for interventions" with "[s]trategies [that] include close monitoring and correction of perioperative hypoxemia, hypotension, fluid and electrolyte balance, and severe anemia," I can rest much easier when I turn off the oxygen, ignore the blood pressure, and walk off down the hall to have coffee when patients I anesthetize do not need these "interventions."
Correspondents.
Journal: JAMA (1883)

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
Delayed hemolytic transfusion reactions. An often-missed entity
Authors: D. Solanki
Journal: JAMA (1978)

Delayed hemolytic transfusion reactions in eight persons were manifested solely or primarily by an apparently unexplained posttransfusion decrease in the hematocrit value. Alloantibodies were eventually found in all eight patients, but were sometimes undetectable for as long as 72 hours after the reaction. This did not preclude the occurrence of a new, acute hemolytic reaction. There were three instances of reversible renal failure complicating the reaction. In two patients, some or all of the antibodies became undetectable after four and nine months. In a third, the indirect antiglobulin reactions became considerably weaker after 12 months. Patients previously sensitized to RBC antigens should have available records inspected and a warning device (wristband or wallet card) provided to help prevent reactions caused by an anamnestic antibody rise. (<i>JAMA</i>239:729-731, 1978)