tbuckley/cabot-search huggingface dataset:
Detection of edema associated with myocardial ischemia by computerized tomography in isolated, arrested canine hearts.
Authors: W JPowell, Jwittenberg, R AMaturi, R EDinsmore, S WMiller
Journal: Circulation (1977)

This study was undertaken to determine if computerized tomography (CT scanning) with an EMI cranial scanner could detect edema associated with myocardial ischemia in canine hearts. A localized area of decreased density in the posterior papillary muscle and surrounding myocardium was detected on serial 8 mm CT scan slices of each heart after 60 min of circumflex artery occlusion and 45 min of reflow of blood. The wet/dry weight ratios and previous electron microscope studies of the ischemic posterior papillary muscles revealed edema accumulation. After 1 hour of arterial occlusion and 12 hours of reflow (which produces extensive necrosis and a decrease in the wet/dry ratio) lesions were still discernible but were less consistently as severe. Permanent ligation of the left anterior descending coronary artery and major collateral arteries for 6 hours also resulted in a lesion of decreased density in the distribution of the occluded arteries. Thus, CT scanning can detect, and is a potential means for sequenti...
Effects of dietary omega 3 fatty acids on vascular contractility in preanoxic and postanoxic aortic rings.
Authors: C DMalis, ALeaf, G SVaradarajan, J BNewell, P CWeber, TForce, J VBonventre
Journal: Circulation (1991)

BACKGROUNDVasomotor reactivity may contribute to the pathophysiology of ischemic injury. The atherosclerotic vessel may be particularly susceptible to vasoconstriction because of the damaged endothelial layer with resultant loss of vasodilatory factors. While dietary omega 3 fatty acids have been proposed to protect against vascular occlusion, it is not clear to what extent this results from alterations in the function of platelets or from changes intrinsic to the blood vessel itself.METHODS AND RESULTSThe effects of dietary supplementation with fish oils on vascular contractility were examined in endothelialized and de-endothelialized aortic rings under pre- and postanoxic conditions. De-endothelialization was defined functionally by the loss of acetylcholine-induced vasodilation in norepinephrine-preconstricted aortic rings from rats fed normal rat chow. Three groups of rats were fed diets containing either 20% menhaden oil or 20% beef tallow, both supplemented with 3% corn oil or 23% corn oil for longe...
Integrative Bulk and Single-Cell Profiling of Premanufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy
Authors: Gregory M. Chen, Changya Chen, Rajat K. Das, Peng Gao, Chia-Hui Chen, Shovik Bandyopadhyay, Yang-Yang Ding, Yasin Uzun, Wenbao Yu, Qin Zhu, Regina M. Myers, Stephan A. Grupp, David M. Barrett, Kai Tan
Journal: Cancer Discovery (2021)

The adoptive transfer of chimeric antigen receptor (CAR) T cells represents a breakthrough in clinical oncology, yet both between- and within-patient differences in autologously derived T cells are a major contributor to therapy failure. To interrogate the molecular determinants of clinical CAR T-cell persistence, we extensively characterized the premanufacture T cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy. We performed RNA-sequencing analysis on sorted T-cell subsets from all 71 patients, followed by paired Cellular Indexing of Transcriptomes and Epitopes (CITE) sequencing and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on T cells from six of these patients. We found that chronic IFN signaling regulated by IRF7 was associated with poor CAR T-cell persistence across T-cell subsets, and that the TCF7 regulon not only associates with the favorable naïve T-cell state, but is maintained in effector T cells among patients with long-term CAR T-cell persistence. These findings provide key insights into the underlying molecular determinants of clinical CAR T-cell function. SIGNIFICANCE: To improve clinical outcomes for CAR T-cell therapy, there is a need to understand the molecular determinants of CAR T-cell persistence. These data represent the largest clinically annotated molecular atlas in CAR T-cell therapy to date, and significantly advance our understanding of the mechanisms underlying therapeutic efficacy.This article is highlighted in the In This Issue feature, p. 2113.
Thymosin β4 protects against aortic aneurysm via endocytic regulation of growth factor signaling
Authors: Sonali Munshaw, Susann Bruche, Andia N. Redpath, Alisha Jones, Jyoti Patel, Karina N. Dubé, Regent Lee, Svenja S. Hester, Rachel Davies, Giles Neal, Ashok Handa, Michael Sattler, Roman Fischer, Keith M. Channon, Nicola Smart
Journal: Journal of Clinical Investigation (2021)

Vascular stability and tone are maintained by contractile smooth muscle cells (VSMCs). However, injury-induced growth factors stimulate a contractile-synthetic phenotypic modulation which increases susceptibility to abdominal aortic aneurysm (AAA). As a regulator of embryonic VSMC differentiation, we hypothesized that Thymosin β4 (Tβ4) may function to maintain healthy vasculature throughout postnatal life. This was supported by the identification of an interaction with low density lipoprotein receptor related protein 1 (LRP1), an endocytic regulator of platelet-derived growth factor BB (PDGF-BB) signaling and VSMC proliferation. LRP1 variants have been implicated by genome-wide association studies with risk of AAA and other arterial diseases. Tβ4-null mice displayed aortic VSMC and elastin defects that phenocopy those of LRP1 mutants, and their compromised vascular integrity predisposed them to Angiotensin II-induced aneurysm formation. Aneurysmal vessels were characterized by enhanced VSMC phenotypic modulation and augmented PDGFR-β signaling. In vitro, enhanced sensitivity to PDGF-BB upon loss of Tβ4 was associated with dysregulated endocytosis, with increased recycling and reduced lysosomal targeting of LRP1-PDGFR-β. Accordingly, the exacerbated aneurysmal phenotype in Tβ4-null mice was rescued upon treatment with the PDGFR-β antagonist Imatinib. Our study identifies Tβ4 as a key regulator of LRP1 for maintaining vascular health, and provides insights into the mechanisms of growth factor-controlled VSMC phenotypic modulation underlying aortic disease progression.
Nitric oxide mediates flow-dependent epicardial coronary vasodilation to changes in pulse frequency but not mean flow in conscious dogs.
Authors: J MCanty, J SSchwartz
Journal: Circulation (1994)

BACKGROUNDAlthough epicardial coronary arteries dilate in response to changes in flow, the mechanisms responsible for this and the mechanical stimuli that are sensed by the endothelium are not completely defined. We performed the present study to determine the importance of nitric oxide in eliciting epicardial dilation to sustained changes in mean flow and pulse frequency in the coronary circulation of conscious dogs.METHODS AND RESULTSDogs were chronically instrumented with a circumflex coronary occluder, piezoelectric crystals to measure epicardial diameter, and a coronary artery catheter placed distal to the crystals for intracoronary drug infusion. Studies were conducted in dogs in the conscious state. We inhibited nitric oxide production by administering the arginine analog N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg IV), which attenuated the epicardial artery diameter changes to left atrial infusions of acetylcholine (10 micrograms/min) from 140 +/- 23 (+/- SEM) to 46 +/- 20 microns (P <...
Comparison of the defibrillation threshold and the upper limit of ventricular vulnerability.
Authors: P SChen, NShibata, E GDixon, R OMartin, R EIdeker
Journal: Circulation (1986)

To examine the relationship between the defibrillation threshold and the strength of shocks that induce ventricular fibrillation during the vulnerable period, we determined the defibrillation threshold in 22 open-chest dogs using epicardial defibrillation electrodes with the cathode at the ventricular apex and the anode at the right atrium. We also determined whether there was an upper limit of shock strength that induces fibrillation in the vulnerable period by giving shocks of various energy through these same electrodes during the repolarization phase of paced rhythm. The above determinations were also made with the anode at the ventricular apex and the cathode at the right atrium in eight of the dogs and with the cathode at the ventricular apex and the anode at the left atrium in another eight of the dogs. In all dogs for all electrode configurations, there was an upper limit to the shock strength that induced ventricular fibrillation during the vulnerable period. Depending on the electrode combinatio...
アジュバント内分泌療法へのゾレドロン酸(ZOL)追加はホルモン応答性早期乳房腫瘍(HREBC)の閉経前女性の無病生存(DF)及び非再発生存(RFS)を改善する:オーストリア乳房腫瘍及び結腸直腸腫瘍研究グループ12(ABCSG-12)試験の多変量解析
Authors: M Gnant, B Mineritsch, W Schippinger, G Luschin-Ebengreuth, S Poestlberger, C Menzel, R Jakesz, E Kubista, C Marth, R Greil
Journal: Annals of Oncology (2009)
The bruit of carotid stenosis versus radiated basal heart murmurs. Differentiation by phonoangiography.
Authors: J PKistler, R SLees, JFriedman, MPressin, J PMohr, G SRoberson, R GOjemann
Journal: Circulation (1978)

Phonoangiography, quantitative analysis of arterial bruits, has been shown to provide accurate noninvasive diagnosis of uncomplicated carotid arterial stenosis, but had not been tested where cervical bruits from other sources were present. In this study, 27 carotid bruits in 15 consecutive patients with carotid bruits and basal heart murmurs were analyzed by phonoangiography. Tape recordings were made over the base of the heart and along the course of the carotid arteries in the neck; spectral analysis was performed as previously described. The spectral shape of the basal heart murmurs was recognizable and amplitude decreased with distance from the heart, althouth a secondary, lower amplitude, maximum often occurred over the carotid bifurcation. Intrinsic carotid bruits, by contrast, were always maximal over the bifurcation, and although they radiated both proximally and distally, were not detectable over the chest wall. In quantitative terms, the correct diagnosis as to the presence and extent of carotid...
Esophageal Testing of Patients with Noncardiac Chest Pain or Dysphagia
Authors: Philip O. Katz, Christine B. Dalton, Joel E. Richter, Wallace C. Wu, Donald O. Castell
Journal: Annals of Internal Medicine (2020)

Abstract Records from 910 patients referred to our clinical esophageal manometry laboratory for evaluation of noncardiac chest pain between January 1983 and December 1985 were reviewed and compared...
5-Year Follow-up of Patients After Hybrid-Apc of Barrett’s Esophagus With Dysplasia: Case-Series Results
Authors: S Kashin, N Vidyaeva, R Kuvaev, E Kraynova, H Manner
Journal: Endoscopy (2021)

Aims The purpose of present study was to evaluate long-term efficacy and safety of new Hybrid-APC therapy for dysplastic Barrett’s esophagus (BE) after onsite training.
Thromboxane A2 mediates increased pulmonary microvascular permeability following limb ischemia.
Authors: J MKlausner, I SPaterson, GGoldman, LKobzik, C RValeri, DShepro, H BHechtman
Journal: Circulation Research (1989)

Lower torso ischemia and reperfusion lead to respiratory dysfunction characterized by pulmonary hypertension and increased lung microvascular permeability. This is associated with lung leukosequestration and thromboxane (TX) generation. This study tests the role of elevated TX levels following muscle ischemia in mediating remote lung injury. Anesthetized sheep prepared with chronic lung lymph fistulae underwent 2 hours of bilateral hind limb tourniquet ischemia. In untreated controls (n = 7), 1 minute after reperfusion there was a transient increase in plasma immunoreactive (i)-TXB2 levels from 211 to 735 pg/ml (p less than 0.05), and at 30 minutes, lung lymph i-TXB2 levels rose from 400 to 1,005 pg/ml (p less than 0.05). At 1 minute, the mean pulmonary arterial pressure (MPAP) increased from 13 to 38 mm Hg (p less than 0.05) and pulmonary microvascular pressure (Pmv) from 7 to 18 mm Hg (p less than 0.05). Lung lymph flow (QL) rose from 4.3 to 8.3 ml/30 min (p less than 0.05), the lymph/plasma (L/P) prote...
Living with artificial valves.
Authors: J R Belcher
Journal: BMJ (1978)

macrocytosis-may be caused solely by direct alcohol toxicity remains in doubt, but on some occasions34 alcohol may possibly induce macrocytic and even megaloblastic changes in patients with normal folate and B12 stores.Indeed, macrocytosis is so common in alcoholics that even if we understand its patho- genesis only incompletely its use as a screening test for alcoholism seems assured.
Brain adenosine production in the rat during 60 seconds of ischemia.
Authors: H RWinn, RRubio, R MBerne
Journal: Circulation Research (1979)

In rats, cerebral perfusion pressure were altered abruptly by aortic transection to determine the production by ischemic brain of adenosine and its metabolites, inosine and hypoxanthine. Brain samples were obtained after 0, 5, 10, 15, 30, and 60 seconds of ischemia. Also measured were ATP, ADP, AMP, phosphocreatine (PCr), lactate, and pyruvate. Blood pressure was monitored continuously, and arterial PO2, PCO2, and pH were measured just prior to induction of ischemia. Adenosine was elevated t 2.30 +/- 0.31 (SE) nmol/g at 5 seconds from a control value of 0.96 +/- 0.07. A significant elevation of adenosine continued to 60 seconds (5.50 +/- 1.24). Furthermore, inosine showed a progressive upward trend during the entire 60 seconds of ischemia, whereas no change in hypoxanthine occurred between the moment of transection (31.81 +/- 2.01 nmol/g) and 60 seconds of ischemia (34.72 +/- 2.93). PCr decreased by 1.24 mumol/g within the first 5 seconds. After the onset of hypotension, significant changes did not occur ...
Dysregulation of the ASPP Protein Family (Apoptosis Stimulating Proteins of TP53) Is a Common Feature in High-Risk Acute Myeloid Leukemia (AML)
Authors: Kerstin Maria Kampa-Schittenhelm, Max Kaiser, Mihada Bajrami Saipi, Bianca Walter, Gunnar Blumenstock, Lothar Kanz, Marcus M Schittenhelm
Journal: Blood (2017)
Quantitative studies of microcirculatory structure and function. III. Microvascular hemodynamics of cat mesentery and rabbit omentum.
Authors: B WZweifach, H HLipowsky
Journal: Circulation Research (1977)

We made simultaneous measurements of intravascular pressure and red blood cell velocity for vessels which make up the modular configuration of microvascular networks in mesentery and omentum. An analysis of these variables and the computed volumetric flow rates is presented for arterioles which had a maximum diameter of 56 micrometer through the true capillaries (typically 7 micrometer for mesentery and 8 micrometer for omentum) to 56-micrometer venules. The spatial variance of pressure and flow is related to topographical features of each network. Vascularization statistics for each network are presented and demonstrate a unique ratio of potential microvascular exchange area to module planar area, with values of 0.71 +/- 0.22 (SD) for omentum and 0.19 /- 0.03 (SD) for mesentery. Analysis of the volumetric flow rate for each module demonstrates a linear relationship to the planar area of tissue serviced by each modular network. In situ perfusion rates of 1180 ml/min per 100 g and 105 ml/min per 100 g w...
Excellent Outcome for Pediatric Patients With High-Risk Hodgkin Lymphoma Treated With Brentuximab Vedotin and Risk-Adapted Residual Node Radiation
Authors: Monika L. Metzger, Michael P. Link, Amy L. Billett, Jamie Flerlage, John T. Lucas, Belinda N. Mandrell, Matthew J. Ehrhardt, Nickhill Bhakta, Torunn I. Yock, Alison M. Friedmann, Pedro de Alarcon, Sandra Luna-Fineman, Eric Larsen, Sue C. Kaste, Barry Shulkin, Zhaohua Lu, Chen Li, Susan M. Hiniker, Sarah S. Donaldson, Melissa M. Hudson, Matthew J. Krasin
Journal: Journal of Clinical Oncology (2021)

Brentuximab vedotin, an effective anti-CD30 antibody-drug conjugate approved for use in adults with classical Hodgkin lymphoma (HL), was introduced in this frontline trial to reduce prescribed radiation in children and adolescents with classical HL.Open-label, single-arm, multicenter trial for patients (age ≤ 18 years) with stage IIB, IIIB, or IV classical HL was conducted. Brentuximab vedotin replaced each vincristine in the OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) regimen according to GPOH-HD2002 treatment group 3 (TG3); two cycles of AEPA and four cycles of CAPDac. Residual node radiotherapy (25.5 Gy) was given at the end of all chemotherapy only to nodal sites that did not achieve a complete response (CR) at the early response assessment (ERA) after two cycles of therapy. Primary objectives were to evaluate the safety and efficacy (complete remission at ERA) of this combination and the 3-year event-free (EFS) and overall survival (OS). The trials are registered at ClinicalTrials.gov (identifier: NCT01920932).Of the 77 patients enrolled in the study, 27 (35%) achieved complete remission at ERA and were spared radiation. Patients who were irradiated received radiation to individual residual nodal tissue. At a median follow-up of 3.4 years, the 3-year EFS was 97.4% (SE 2.3%) and the OS was 98.7% (SE 1.6%). One irradiated patient experienced disease progression at the end of therapy and now remains disease free more than 6 years following salvage therapy, and one unexpected death occurred. Only 4% of patients experienced grade 3 neuropathy.The integration of brentuximab vedotin in the frontline treatment of pediatric high-risk HL is highly tolerable, facilitated significant reduction in radiation exposure, and yielded excellent outcomes.
The relevance of platelet and fibrin thromboembolism of the coronary microcirculation, with special reference to sudden cardiac death.
Authors: NEl-Maraghi, EGenton
Journal: Circulation (1980)

The coronary microcirculation was examined for platelet and fibrin thrombi in hearts from 21 normal subjects and 244 cardiac patients, including 168 with ischemic heart disease (IHD) and 76 with other types of heart disease. Seventy-seven cases were sudden cardiac death (SCD). No microthrombi were present in any of the normal hearts, whereas platelet and fibrin thrombin were present in the coronary microcirculation in 32 of 244 cardiac cases (13.1%), including 19 with IHD and 13 with other types of heart disease and after cardiac surgery. The microthrombi were either embolic or represented in situ thrombosis, depending upon the underlying pathologic process. There was no significant difference in the incidence of microthrombi in SCD patients, with IHD (10 of 50, 20%) compared with patients who survived longer (nine of 93, 10%). In SCD patients, however, platelet microthrombin were more frequent in patients less than 45 years of age compared with those older than 45 years of age (p = 0.0002). We concluded ...
Cytokine-specific autoantibodies shape the gut microbiome in autoimmune polyendocrine syndrome type 1
Authors: Anders Ø. Petersen, Martta Jokinen, Damian R. Plichta, Gerhard Liebisch, Wolfram Gronwald, Katja Dettmer, Peter J. Oefner, Hera Vlamakis, Daniel C. Chung, Annamari Ranki, Ramnik J. Xavier
Journal: Journal of Allergy and Clinical Immunology (2021)
Comparative Efficacy and Rapidity of Action for Infliximab vs Ustekinumab in Biologic Naïve Crohn’s Disease
Authors: Neeraj Narula, Emily C.L. Wong, Parambir S. Dulai, Neil K. Sengupta, John K. Marshall, Jean-Frederic Colombel, Walter Reinisch
Journal: Clinical Gastroenterology and Hepatology (2021)
Eus-Guided Choledochoduodenostomy Using a Lumen-Apposing Metal Stent for Malignant Distal Biliary Obstruction: a Retrospective Multicenter Analysis
Authors: A Fugazza, C Fabbri, R Di Mitri, MC Petrone, M Colombo, M Ballarè, L Cugia, A Amato, E Forti, G De Nucci, M Manno, V Pollino, C Binda, R Macchiarelli, N Leone, R Badas, M Lovera, E Armellini, A Redaelli, B Mangiavillano, ML Brancaccio, F Attili, T Togliani, G Aragona, E Conte, M Maida, E Sinagra, A Repici, I Tarantino, A Anderloni
Journal: Endoscopy (2021)

Aims Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) with lumen apposing metal stent (LAMS) has emerged as a procedure with encouraging results in terms of safety and effectiveness in patients with malignant distal biliary obstruction and failed endoscopic retrograde cholangiopancreatography (ERCP).
"Pressure-volume" relations in isolated cat trabecula.
Authors: GElzinga, NWesterhof
Journal: Circulation Research (1981)

We studied isolated cat trabecula under conditions closely resembling those present for muscle fibers in the left ventricular wall. The purpose of the study was to see if muscle contraction under those circumstances could be described by a time-varying compliance as reported for intact canine left ventricle. We found the time of the end of systole to depend on the history of contraction. This time varied between 100 and 160 msec as measured from the onset of contraction. Similar dependency, although less percentage-wise, was found by reanalysis for intact feline left ventricles. We conclude that the behavior of the canine left ventricle as a time-varying compliance may be related to the complex organization of the cardiac muscle fibers in the wall of the heart rather than to muscle properties.
Determinants of the recovery of right ventricular performance following experimental chronic right coronary artery occlusion.
Authors: S BLaster, T JShelton, BBarzilai, J AGoldstein
Journal: Circulation (1993)

BACKGROUNDPatients with acute ischemic right ventricular dysfunction often develop hemodynamic compromise, yet most manifest spontaneous early clinical improvement and later recovery of global right ventricular performance. This study was designed to delineate the determinants of right ventricular performance following chronic right coronary artery occlusion.METHODS AND RESULTSThrombotic right coronary artery occlusion was induced in 16 closed-chest dogs. Acute occlusion depressed right ventricular free wall motion (motion score, 1.0 +/- 0.0 to 3.4 +/- 0.1*) and global performance (right ventricular fractional area change, 29.2 +/- 1.8% to 2.3 +/- 1.9%*). There was right ventricular dilatation and reversed septal curvature, with elevated and equalized diastolic filling pressures. At 5 days, despite persistent severe right ventricular free wall dysfunction (motion score, 3.4 +/- 0.1 to 2.7 +/- 0.1*), global right ventricular performance improved (fractional area change, 2.3 +/- 1.9% to 17.0 +/- 3.8%*), in ...
Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease. Implications for the mechanism of the training response.
Authors: W RHiatt, E EWolfel, R HMeier, J GRegensteiner
Journal: Circulation (1994)

BACKGROUNDIn patients with intermittent claudication, a supervised walking exercise program increases peak exercise performance and community-based functional status. Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment. However, the potential benefits of training modalities other than walking exercise, such as strength training, have not been critically evaluated in this patient population. The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance.METHODS AND RESULTSTwenty-nine patients with disabling claudication were randomized to 12 weeks of supervised walking exercise on a treadmill (3 h/wk at a work intensity sufficient to produce claudication), strength training (3 h/wk of resistive training of five muscle groups ...