tbuckley/cabot-search huggingface dataset:
Oncolytic herpesvirus expressing PD-L1 BiTE for cancer therapy: exploiting tumor immune suppression as an opportunity for targeted immunotherapy
Authors: Hena Khalique, Richard Baugh, Arthur Dyer, Eleanor M. Scott, Sally Frost, Sarah Larkin, Janet Lei-Rossmann, Leonard W. Seymour
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Programmed death-ligand 1 (PD-L1) is an important immune checkpoint protein that can be regarded as a pan-cancer antigen expressed by multiple different cell types within the tumor. While antagonizing PD-L1 is well known to relieve PD-1/PD-L1-mediated T cell suppression, here we have combined this approach with an immunotherapy strategy to target T cell cytotoxicity directly toward PD-L1-expressing cells. We developed a bi-specific T cell engager (BiTE) crosslinking PD-L1 and CD3ε and demonstrated targeted cytotoxicity using a clinically relevant patient-derived ascites model. This approach represents an immunological ‘volte-face’ whereby a tumor immunological defense mechanism can be instantly transformed into an Achilles’ heel for targeted immunotherapy. Methods The PD-L1 targeting BiTE comprises an anti-PD-L1 single-chain variable fragment (scFv) or nanobody (NB) domain and an anti-CD3 scFv domain in a tandem repeat. The ability to activate T cell cytotoxicity toward PD-L1-expressing cells was established using human carcinoma cells and PD-L1-expressing human (‘M2’) macrophages in the presence of autologous T cells. Furthermore, we armed oncolytic herpes simplex virus-1 (oHSV-1) with PD-L1 BiTE and demonstrated successful delivery and targeted cytotoxicity in unpurified cultures of malignant ascites derived from different cancer patients. Results PD-L1 BiTE crosslinks PD-L1-positive cells and CD3ε on T cells in a ‘pseudo-synapse’ and triggers T cell activation and release of proinflammatory cytokines such as interferon-gamma (IFN-γ), interferon gamma-induced protein 10 (IP-10) and tumour necrosis factor-α (TNF-α). Activation of endogenous T cells within ascites samples led to significant lysis of tumor cells and M2-like macrophages (CD11b+CD64+ and CD206+/CD163+). The survival of CD3+ T cells (which can also express PD-L1) was unaffected. Intriguingly, ascites fluid that appeared particularly immunosuppressive led to higher expression of PD-L1 on tumor cells, resulting in improved BiTE-mediated T cell activation. Conclusions The study reveals that PD-L1 BiTE is an effective immunotherapeutic approach to kill PD-L1-positive tumor cells and macrophages while leaving T cells unharmed. This approach activates endogenous T cells within malignant ascites, generates a proinflammatory response and eliminates cells promoting tumor progression. Using an oncolytic virus for local expression of PD-L1 BiTE also prevents ‘on-target off-tumor’ systemic toxicities and harnesses immunosuppressive protumor conditions to augment immunotherapy in immunologically ‘cold’ clinical cancers.
Fibrillar collagen and myocardial stiffness in the intact hypertrophied rat left ventricle.
Authors: J EJalil, C WDoering, J SJanicki, RPick, S GShroff, K TWeber
Journal: Circulation Research (1989)

This study tested the hypothesis that with hypertrophy, the proportion, distribution, and structural alignment of fibrillar collagen are important determinants of myocardial stiffness. Toward this end, the collagen volume fraction (morphometry), the transmural or subendocardial distribution of collagen, and the structural arrangement of fibrillar collagens (picrosirius red) were examined in the hypertrophied ventricle secondary to pressure overload (abdominal aorta banding or perinephritis), isoproterenol, and pressure overload plus isoproterenol. In the same hearts, the slopes of the systolic and diastolic stress-strain relations of the left ventricle, representing its active and passive stiffness, respectively, were obtained. In comparison with controls, we found 1) for a moderate rise in transmural collagen, active and passive stiffness increased with pressure-overload hypertrophy; 2) following isoproterenol alone there was a marked increase in subendocardial collagen, and active and passive stiffness ...
Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051)
Authors: A.C. Lockhart, C.E. Reed, P.A. Decker, B.F. Meyers, M.K. Ferguson, A.R. Oeltjen, J.B. Putnam, S.D. Cassiv, A.J. Montero, T.E. Schefter
Journal: Annals of Oncology (2018)

Ann Oncol 2014; 25: 1039–1044 (doi: 10.1093/annonc/mdu091) The following funding statement was missing from the original manuscript: ‘Supported by NIH grants U10CA180821 and U10CA180882 to the Alliance for Clinical Trials in Oncology.’ This has now been amended in the online version. Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051)Annals of OncologyVol. 25Issue 5PreviewPreoperative chemoradiotherapy (CRT) improves outcomes in patients with locally advanced but resectable adenocarcinoma of the esophagus. ACOSOG Z4051 evaluated CRT with docetaxel, cisplatin, and panitumumab (DCP) in this patient group with a primary end point of a pathologic complete response (pCR) ≥35%. Full-Text PDF Open Archive
Inhibition of cyclic flow variations in stenosed canine coronary arteries by thromboxane A2/prostaglandin H2 receptor antagonists.
Authors: J HAshton, J MSchmitz, W BCampbell, M LOgletree, SRaheja, A LTaylor, CFitzgerald, L MBuja, J TWillerson
Journal: Circulation Research (1986)

We tested the hypothesis that thromboxane A2 and thromboxane A2/PGH2 receptor occupation are important in mediating cyclical reductions in coronary blood flow (CFVs) in concentrically narrowed canine coronary arteries. Two potent and selective thromboxane A2/PGH2 receptor antagonists, SQ29,548 and SQ28,668 eliminated CFVs and restored a normal pattern of blood flow through the severely narrowed vessels in 77 and 75% of the dogs, respectively. CFVs were eliminated within several minutes of an intravenous bolus injection of SQ29,548 or SQ28,688. A continuous infusion of SQ29,548 (0.2 mg/kg X min) prevented the recurrence of CFVs throughout the duration of its infusion. Left atrial infusion of the thromboxane A2 mimetic, U46619, restored CFVs in 5 of 8 SQ29,548-treated and in 5 of 7 SQ28,668-treated dogs. Circulating concentrations of the stable metabolites of TxA2 and PGI2, TxB2 and 6-keto-PGF1 alpha, respectively, were unaffected by administration of SQ29,548. However, stenosed vascular segments of the lef...
The effects of antithrombotic drugs in patients with left ventricular thrombi: assessment with indium-111 platelet imaging and two-dimensional echocardiography.
Authors: J RStratton, J LRitchie
Journal: Circulation (1984)

Patients with left ventricular thrombi not caused by recent myocardial infarction were prospectively studied by indium-111 platelet imaging and two-dimensional echocardiography to determine the reproducibility of these techniques and the short-term effects of sulfinpyrazone (200 mg four times daily), aspirin (325 mg three times daily) plus dipyridamole (75 mg three times daily), and full-dose warfarin. At baseline, all patients underwent indium-111 platelet imaging and echocardiography, and the results were positive for thrombus. In six patients on no antithrombotic drug therapy, repeat platelet scans and echocardiographic studies at 6.0 +/- 3.3 weeks remained positive and were unchanged. In seven patients studied on sulfinpyrazone, three platelet scans became negative, two became equivocal, and two were unchanged; the presence and size of thrombus was constant by echocardiography in all seven patients. Of the six patients studied on aspirin plus dipyridamole, one platelet scan became negative, those of t...
Dynamic dermoscopic and reflectance confocal microscopic changes of melanocytic lesions excised during follow up
Authors: Alessandra Grazia Condorelli, Francesca Farnetani, Silvana Ciardo, Johanna Chester, Shaniko Kaleci, Ignazio Stanganelli, Laura Mazzoni, Serena Magi, Victor Desmond Mandel, Marica Mirra, Riccardo Pampena, Margherita Raucci, Caterina Longo, Giovanni Pellacani
Journal: Journal of the American Academy of Dermatology (2021)
Cardiac transplantation: recipient selection, donor procurement, and medical follow-up. A statement for health professionals from the Committee on Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association.
Authors: J BO'Connell, R CBourge, M RCostanzo-Nordin, D JDriscoll, J PMorgan, E ARose, B FUretsky
Journal: Circulation (1992)
Noninvasive detection of pulmonary hypertension in patent ductus arteriosus by pulsed Doppler echocardiography.
Authors: J GStevenson, IKawabori, W GGuntheroth
Journal: Circulation (1979)

Twenty-five patients with proven patent ductus arteriosus were examined by pulsed Doppler echocardiography (PDE) before invasive assessment. Ten patients had normal pulmonary artery pressures, and by PDE, pandiastolic ductal flow. Fifteen patients had elevation of mean pulmonary artery pressure, and by PDE, all had abbreviations of diastolic ductal flow. PDE correctly distinguished between patients with normal pressure and those with evidence of pulmonary hypertension; the ECG did not allow such differentiation. Detection by PDE of pulmonary hypertension complicating patent ductus arteriosus appears to be clinically useful.
Axillary Lymph Nodes Hypermetabolism After BNT162b2 mRNA COVID-19 Vaccination in Cancer Patients Undergoing 18F-FDG PET/CT
Authors: Hanna Bernstine, Miriam Priss, Tamer Anati, Olga Turko, Miguel Gorenberg, Adam Peter Steinmetz, David Groshar
Journal: Clinical Nuclear Medicine (2021)

Recognition of the pattern of FDG uptake in hypermetabolic axillary lymph nodes (HALs) and association with recent messenger RNA (mRNA) vaccination are important to prevent patient anxiety and further needless examinations or costly biopsies in cancer patients.This study was a retrospective cohort study in a single tertiary care institution. We investigate the occurrence and pattern of HAL on FDG PET/CT scans from 650 consecutive cancer patients with recent BNT162b2 mRNA COVID-19 vaccination.Between December 20, 2020, and February 8, 2021, 650 patients (351 female patients [54%]; mean age, 68.9 years) had recent mRNA COVID-19 vaccination and an FDG PET/CT scan. HALs were found in 57 (14.5%) of 394 patients (95% confidence interval [CI], 10.9%-18.7%) 12.3 ± 5.9 (1-22) days after dose 1 and in 111 (43.3%) of 256 patients (95% CI, 35.3%-52.2%; P < 0.0001) after 7.5 ± 5.4 (1-22) days after dose 2. There was no difference between dose 1 and dose 2 concerning SUVmax (3.7 ± 1.8 [1.3-11.3] and 4.5 ± 3.9 [1.4-26.3], P = 0.13, respectively), SUVmean (2.1 ± 1.0 [0.7-6.5] and 2.7 ± 2.4 [0.8-17], P = 0.08, respectively), and reactogenicity volume (2.7 ± 2.3 [0.2-11.6] cm3 and 2.7 ± 2.4 [0.2-15.5] cm3, P = 0.98, respectively). There was no difference in number and in size of positive lymph nodes between dose 1 and dose 2: 3.2 ± 2.2 (1-10) and 3.7 ± 2.4 (1-12) (P = 0.18), and 1.4 ± 0.4 cm (0.7-2.5 cm) and 1.5 ± 0.4 cm (0.6-3.2 cm) (P = 0.75), respectively.A cluster pattern of hypermetabolic ipsilateral small axillary lymph nodes is common after mRNA COVID-19 vaccination, mainly after the second injection.
Physiological hyperinsulinemia inhibits myocardial protein degradation in vivo in the canine heart.
Authors: L HYoung, D MDahl, DRauner, E JBarrett
Journal: Circulation Research (1992)

Myocardial protein turnover in vivo was examined in anesthetized dogs following a 16- or 36-hour fast and again during a hyperinsulinemic (2 mU/kg per minute) euglycemic clamp with or without amino acid replacement or during saline infusion. We measured myocardial phenylalanine balance and rates of protein synthesis and degradation, using the extraction of intravenously infused L-[ring-2,6-3H]phenylalanine and the dilution of its specific activity across the heart at isotopic steady state. After both a 16-hour (n = 19) and 36-hour fast (n = 10), there was net myocardial release of phenylalanine indicated by the negative balances for phenylalanine of -52 +/- 9 (p less than 0.001) and -38 +/- 9 (p less than 0.005) nmol/min, respectively. Overall, the basal rate of myocardial protein degradation was lower in the 36-hour-fasted animals (81 +/- 13 versus 121 +/- 12 nmol/min, p less than 0.05). Myocardial phenylalanine balance and rates of protein synthesis and degradation did not change during insulin and gluc...
Abstract 15108: Right Ventricular Septal Pacing Preserves Global Left Ventricular Longitudinal Function in Comparison With Apical Pacing: Analysis of Speckle Tracking Echocardiography
Authors: Katsuji Inoue, Hideki Okayama, Kazuhisa Nishimura, Takayuki Nagai, Jun Suzuki, Akiyoshi Ogimoto, Makoto Saito, Go Hiasa, Toyofumi Yoshii, Takumi Sumimoto, Jun-ichi Funada, Jitsuo Higaki
Journal: Circulation (2010)

Background:  RV pacing alters left ventricular (LV) mechanical activation pattern, Resultsing to the adverse impacts on LV function. The global longitudinal strain (GLS) by speckle tracking echocardiography (STE) is reported at a robust predictor of future cardiac events over standard LV ejection fraction and wall motion scoring. Objectives: The objective of this study was to investigate the acute effect of right ventricular apical (RVA) and septal pacing (RVS) on LV global function using STE.   Methods:  103 patients (74 ± 9 years) with symptomatic bradyarrhythmia and preserved LV ejection fraction and 50 age-matched control subjects were studied. Site of pacemaker insertion was randomly assigned into two groups in participant patients (RVA: n= 51, RVS: n=52). After insertion, patients underwent echocardiographic study during RV pacing. LV global strain parameters were analyzed using STE.   Results:  The QRS width and LV dyssynchrony indices derived by longitudinal and radial strain were significantly greater in RVA than both the control and RVS. The LV longitudinal dyssynchrony index was significantly related to GLS among patients receiving RVA (R 2 = 0.26, P= 0.0001). The GLS and systolic global longitudinal strain rate (sGLSr) in RVA were the lowest among the 3 groups (GLS: Control: -18.2 ± 2.4%, RVA: -14.3 ± 3.1%, P -1 , RVA: -0.8 ± 0.2 s -1 , P -1  vs RVA, P -1 , RVA: 0.8 ± 0.3 s -1 , P -1 ).   Conclusion:  RVA could reduce LV systolic global longitudinal function in parallel with LV dyssynchrony compared to RVS. RVS could be a better pacing alternative in terms of a less LV dyssynchrony and better global longitudinal function compared to RVA.
Calcitonin gene-related peptide mediates nitroglycerin and sodium nitroprusside-induced vasodilation in feline cerebral arterioles.
Authors: E PWei, M AMoskowitz, PBoccalini, H AKontos
Journal: Circulation Research (1992)

The cerebral vasodilator response induced by topical nitroglycerin and nitroprusside was examined in cats equipped with cranial windows for the observation of the cerebral microcirculation. In cats subjected to chronic unilateral trigeminal ganglionectomy, the vasodilator responses to nitroprusside and nitroglycerin were markedly depressed on the denervated side. Application of a selective calcitonin gene-related peptide (CGRP) antagonist [CGRP(8-37)] on the innervated side reduced the response to nitrodilators to the same extent as seen on the denervated side. The vasodilator response to acetylcholine was unaffected by trigeminal ganglionectomy. CGRP(8-37) almost abolished the vasodilator response to nitroglycerin and sodium nitroprusside and to CGRP, but did not affect the response to adenosine or to adenosine diphosphate. Pretreatment with LY83583, a drug that lowers cyclic GMP levels, diminished the vasodilation to CGRP and to nitroprusside but not to adenosine. We conclude that the nitrovasodilators ...
失明と距離と近見視力障害の世界的な有病率の大きさ,時間的傾向および予測:系統的レビューとメタ分析【Powered by NICT】
Authors: Bourne Rupert R A, Flaxman Seth R, Braithwaite Tasanee, Cicinelli Maria, Das Aditi, Jonas Jost B, Keeffe Jill, Kempen John H, Leasher Janet, Limburg Hans, Naidoo Kovin, Pesudovs Konrad, Resnikoff Serge, Silvester Alex, Stevens Gretchen A, Tahhan Nina, Wong Tien Y, Taylor Hugh R
Journal: The Lancet Global Health (2017)
Shall The Journal be Removed to Washington?
Authors: E. C. Spitzka
Journal: JAMA (1891)

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
Effect of histamine on the energy metabolism of K+-depolarized hog carotid artery.
Authors: J WPeterson
Journal: Circulation Research (1982)

In a previous study (Peterson and Gluck, 1982), activation of hog carotid artery with high-K+ medium caused no increase in aerobic glycolysis (lactic acid production). In contrast, histamine alone is found to stimulate aerobic glycolysis in a tension-dependent fashion (GLuck and Paul, 1977). In this study, the addition of histamine to the already K+-depolarized hog carotid artery induced additional contraction, elevated tissue cyclic adenosine 3',5'-monophosphate [cAMP] levels, coupled the rate of aerobic glycolysis to external [Ca++] and isometric tension, and caused suprabasal energy utilization to exceed that required to support the contraction alone by approximately 25%. Increased cytoplasmic free-[Ca++] per se does not stimulate aerobic glycolysis. In the presence of histamine, however, aerobic glycolysis is Ca++-sensitive. Whereas a cycle of Ca++ depletion and restoration has only a small effect on basal metabolic rates in arteries activated with high-K+ alone, the same procedure with arteries stimu...
International gestational age-specific centiles for blood pressure in pregnancy from the INTERGROWTH-21st Project in 8 countries: A longitudinal cohort study
Authors: Lauren J. Green, Stephen H. Kennedy, Lucy Mackillop, Stephen Gerry, Manorama Purwar, Eleonora Staines Urias, Leila Cheikh Ismail, Fernando Barros, Cesar Victora, Maria Carvalho, Eric Ohuma, Yasmin Jaffer, J. Alison Noble, Michael Gravett, Ruyan Pang, Ann Lambert, Enrico Bertino, Aris T. Papageorghiou, Cutberto Garza, Zulfiqar Bhutta, José Villar, Peter Watkinson
Journal: PLoS Medicine (2021)

Gestational hypertensive and acute hypotensive disorders are associated with maternal morbidity and mortality worldwide. However, physiological blood pressure changes in pregnancy are insufficiently defined. We describe blood pressure changes across healthy pregnancies from the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Fetal Growth Longitudinal Study (FGLS) to produce international, gestational age-specific, smoothed centiles (third, 10th, 50th, 90th, and 97th) for blood pressure.Secondary analysis of a prospective, longitudinal, observational cohort study (2009 to 2016) was conducted across 8 diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States of America. We enrolled healthy women at low risk of pregnancy complications. We measured blood pressure using standardised methodology and validated equipment at enrolment at <14 weeks, then every 5 ± 1 weeks until delivery. We enrolled 4,607 (35%) women of 13,108 screened. The mean maternal age was 28·4 (standard deviation [SD] 3.9) years; 97% (4,204/4,321) of women were married or living with a partner, and 68% (2,955/4,321) were nulliparous. Their mean body mass index (BMI) was 23.3 (SD 3.0) kg/m2. Systolic blood pressure was lowest at 12 weeks: Median was 111.5 (95% CI 111.3 to 111.8) mmHg, rising to a median maximum of 119.6 (95% CI 118.9 to 120.3) mmHg at 40 weeks' gestation, a difference of 8.1 (95% CI 7.4 to 8.8) mmHg. Median diastolic blood pressure decreased from 12 weeks: 69.1 (95% CI 68.9 to 69.3) mmHg to a minimum of 68.5 (95% CI 68.3 to 68.7) mmHg at 19+5 weeks' gestation, a change of -0·6 (95% CI -0.8 to -0.4) mmHg. Diastolic blood pressure subsequently increased to a maximum of 76.3 (95% CI 75.9 to 76.8) mmHg at 40 weeks' gestation. Systolic blood pressure fell by >14 mmHg or diastolic blood pressure by >11 mmHg in fewer than 10% of women at any gestational age. Fewer than 10% of women increased their systolic blood pressure by >24 mmHg or diastolic blood pressure by >18 mmHg at any gestational age. The study's main limitations were the unavailability of prepregnancy blood pressure values and inability to explore circadian effects because time of day was not recorded for the blood pressure measurements.Our findings provide international, gestational age-specific centiles and limits of acceptable change to facilitate earlier recognition of deteriorating health in pregnant women. These centiles challenge the idea of a clinically significant midpregnancy drop in blood pressure.
Shall The Journal be Removed to Washington?
Authors: H. C. Markham
Journal: JAMA (1891)

<h3>To the Editor:</h3> —The writer's subscription (as have those for every former one) for Vol. xv ofThe Journalwill soon be forthcoming, and for the fact above he would regret a break in the file. To the ordinary observer the proposition to removeThe Journalto the Capital or elsewhere must have in its favor some occult reason or grounds, so palpable and strong are the objections. In all forms of journalism the argument for a central place of publication is vital, but in the special case ofThe Journal, it is tenfold stronger. The word "Association" gives the key to this statement. Surely reasons, at the present sufficient, and daily augmenting—not to mention success—would induce the common mind to think and say "The Journalis exactly where it should be." Yours truly, Independence, Iowa, Dec. 27, 1890.
Synthesis of lipoxygenase and epoxygenase products of arachidonic acid by normal and stenosed canine coronary arteries.
Authors: MRosolowsky, J RFalck, J TWillerson, W BCampbell
Journal: Circulation Research (1990)

Coronary vascular injury promotes blood cell-vessel wall interactions that influence arachidonic acid metabolism and coronary blood flow patterns. Since lipoxygenase and cytochrome P-450 epoxygenase metabolites of arachidonic acid are synthesized by vascular and inflammatory cells and have a variety of important biological actions, we investigated the metabolism of arachidonic acid by these pathways in normal and stenosed, endothelially injured canine coronary arteries. We found and confirmed by gas chromatography/mass spectrometry that primarily 12- and 15-hydroxyeicosatetraenoic acids (HETEs) are synthesized by both coronary artery segments. Lesser amounts of 11-, 9-, 8-, and 5-HETEs are also produced. 15-Ketoeicosatetraenoic acid is also synthesized. The synthesis of 14C-HETEs is fivefold to 10-fold greater by the stenosed than the normal coronary artery. Specific radioimmunoassays indicated that the stenosed coronary artery synthesized 93 +/- 14 and 1,102 +/- 154 ng/g of tissue of 15- and 12-HETE, res...