tbuckley/cabot-search huggingface dataset:
Resident PW1 <sup>+</sup> Progenitor Cells Participate in Vascular Remodeling During Pulmonary Arterial Hypertension
Authors: France Dierick, Tiphaine Héry, Bénédicte Hoareau-Coudert, Nathalie Mougenot, Virginie Monceau, Caroline Claude, Mihaela Crisan, Vanessa Besson, Peter Dorfmüller, Gilles Marodon, Elie Fadel, Marc Humbert, Elisa Yaniz-Galende, Jean-Sébastien Hulot, Giovanna Marazzi, David Sassoon, Florent Soubrier, Sophie Nadaud
Journal: Circulation Research (2016)

Pulmonary arterial hypertension is characterized by vascular remodeling and neomuscularization. PW1(+) progenitor cells can differentiate into smooth muscle cells (SMCs) in vitro.To determine the role of pulmonary PW1(+) progenitor cells in vascular remodeling characteristic of pulmonary arterial hypertension.We investigated their contribution during chronic hypoxia-induced vascular remodeling in Pw1(nLacZ+/-) mouse expressing β-galactosidase in PW1(+) cells and in differentiated cells derived from PW1(+) cells. PW1(+) progenitor cells are present in the perivascular zone in rodent and human control lungs. Using progenitor markers, 3 distinct myogenic PW1(+) cell populations were isolated from the mouse lung of which 2 were significantly increased after 4 days of chronic hypoxia. The number of proliferating pulmonary PW1(+) cells and the proportion of β-gal(+) vascular SMC were increased, indicating a recruitment of PW1(+) cells and their differentiation into vascular SMC during early chronic hypoxia-induced neomuscularization. CXCR4 inhibition using AMD3100 prevented PW1(+) cells differentiation into SMC but did not inhibit their proliferation. Bone marrow transplantation experiments showed that the newly formed β-gal(+) SMC were not derived from circulating bone marrow-derived PW1(+) progenitor cells, confirming a resident origin of the recruited PW1(+) cells. The number of pulmonary PW1(+) cells was also increased in rats after monocrotaline injection. In lung from pulmonary arterial hypertension patients, PW1-expressing cells were observed in large numbers in remodeled vascular structures.These results demonstrate the existence of a novel population of resident SMC progenitor cells expressing PW1 and participating in pulmonary hypertension-associated vascular remodeling.
Abstract P349: Dietary Sodium Intake according to the Hypertension Management Status: The Fourth Korea National Health and Nutrition Examination Survey.
Authors: Won Joon Lee, Hyeon Chang Kim, Sun Min Oh, Dong Phil Choi, Hye Min Cho, Ju-Mi Lee, Il Suh
Journal: Circulation (2012)

Introduction : High sodium intake is an established risk factor for hypertension and cardiovascular diseases. The average sodium intake in Koreans was estimated at 4,645mg/day, which was more than two times compared to the recommended amount, 2000mg/day. We assessed whether people who diagnosed with hypertension or treated for hypertension consume less sodium than those without hypertension. Methods : The present study analyzed data from a total of 6,577 Koreans (3,816 women and 2,761 men) aged 40 years and older, participated in the Korea National Health and Nutrition Examination Survey (KNHANES IV, 2007-2008). Participants were classified into five groups as follows: normal blood pressure, pre-hypertension, hypertension without treatment, hypertension with treatment, and hypertension with complications. The association between sodium intake and hypertension management status was estimated using exponential regression coefficient, adjusted for potential confounders including age, energy intake, body mass index, income, education, marriage, occupation, the frequency of eating out and effort to lower sodium intake. Results : In women, the median sodium intake tended to decrease according to the following groups; 3,708mg in normal blood pressure, 3,515mg in pre-hypertension, 3,191mg in hypertension without treatment, 3,113mg in hypertension with treatment, and 2,862mg in hypertension with complications (P for trend &lt; 0.001). In men, a similar trend was shown, but sodium consumption was the highest in the prehypertension group; 5,099mg in normal blood pressure, 5,353mg in pre-hypertension, 5,118mg in hypertension without treatment, 4,708mg in hypertension with treatment, and 3,798mg in hypertension with complications (P for trend &lt; 0.001). After controlling for potential confounders (energy intake, body mass index, occupation, the frequency of eating out), the trend was not significant both in women (P for trend= 0.887) and men (P for trend=0. 204). Only in men with prehypertension, sodium intake was 1.08 times higher than that in normal blood pressure group (P = 0.025). Conclusions : The present study showed that Korean women and men consumed sodium more than the recommended amount regardless of the presence of, the treatment for, or knowing the complications of hypertension. Moreover, men with prehypertension consumed the highest amount of sodium.
Abstract 148: Zoniporide Combined with α-Methylnorepinephrine Appears Highly Effective for Resuscitation from Cardiac Arrest in a Rat Model of Ventricular Fibrillation
Authors: Lorissa Lamoureux, Herbert K Whitehouse, Jeejabai Radhakrishnan, Raúl J Gazmuri
Journal: Circulation (2014)

Background: We have reported in rat and swine models of cardiac arrest that sodium hydrogen exchanger isoform-1 (NHE-1) inhibition facilitates resuscitation, ameliorates myocardial dysfunction, and improves survival. Others have reported that α-methylnorepinephrine (α-MNE) - a selective α2-adrenoreceptor agonist - is superior to epinephrine given its lack of β-agonist effects. We examined in a rat model of VF and closed-chest resuscitation the effects of combining the NHE-1 inhibitor zoniporide (ZNP) with α-MNE. Methods: VF was electrically induced in 32 male retired breeder Sprague-Dawley rats and left untreated for 8 minutes after which resuscitation was attempted by an 8 minute interval of chest compression and delivery of electrical shocks. Rats were randomized 1:1:1:1 to receive a 3 mg/kg bolus of ZNP or 0.9% NaCl before starting chest compression and a 100 μg/kg bolus of α-MNE or its vehicle at minute 2 of chest-compressions establishing 4 groups of 8 rats each. Successfully resuscitated rats were monitored for 240 minutes. Results: The number of rats that had return of spontaneous circulation and then survived 240 min were: α-MNE(-)/ZNP(-) 4 and 2; α-MNE(-)/ZNP(+) 5 and 5; α-MNE(+)/ZNP(-) 2 and 1; and α-MNE(+)/ZNP(+) 7 and 7 yielding a statistically significant effect on overall survival times corresponding to 105 ± 114, 150 ± 124, 58 ± 108, and 210 ± 85 min, respectively (p &lt; 0.045). Post-resuscitation lactate levels were attenuated in all treatment groups with the greatest effect by the α-MNE(+)/ZNP(+) combination without major differences in hemodynamic function (Table). Conclusion: We confirm a beneficial effect resulting from the combination of ZNP (given to attenuate myocardial reperfusion injury) and α-MNE (given to augment peripheral vascular resistance during chest compression without the detrimental actions of epinephrine). The proposed combination may prove to be a highly effective novel strategy for resuscitation from cardiac arrest.
Somatic Mutations in the Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3) Are Associated with Poor Prognosis in Myeloid Malignancies
Authors: Valeria Visconte, Ali Tabarroki, Li Zhang, Aaron T. Gerds, Heesun J. Rogers, Velizar Shivarov, John Barnard, Ramon V. Tiu
Journal: Blood (2014)
DUSP4 phosphatase puts the brakes on DLBCL
Authors: Robert Rickert
Journal: The Journal of Experimental Medicine (2015)

The Journal of Experimental Medicine Communication between cells is vital for maintenance of immune homeostasis and is also required for rapid and effective immune responses.Nowhere is this balance of activity more important than at mucosal surfaces such as the respiratory tract, where resident cells must ignore potentially antigenic inhaled material while responding swiftly to clear viruses and bacteria.In this issue, Bourdonnay et al. describe a novel form of intercellular communication that helps to explain how alveolar macrophages and epithelial cells maintain pulmonary homeostasis.The function of SOCS proteins is to constrain JAK-STAT signaling and repress inflammatory reactions.We do not usually expect to find these intracellular signaling molecules in extracellular compartments, but Bourdonnay et al. showed that lung-resident alveolar macrophages (AMs) were able to secrete SOCS1 within exosomes and SOCS3 within extracellular microparticles.Uptake of these extracellular vesicles by alveolar epithelial cells (AECs) allowed SOCS1 and -3 to suppress STAT signaling following activation by cytokines.The authors demonstrated that this novel extracellular transfer system was promoted by IL-10 and PGE 2 and inhibited by LPS.The phenomenon was demonstrated in a number of model systems including both rats and mice and also, importantly, in human AMs.Moreover, secretion was not simply dependent on expression of SOCS3, because fibroblasts expressed high levels of SOCS3 but did not secrete it.Any in vitro finding needs to be robustly tested in vivo to demonstrate a physiologic effect.The authors showed that SOCS3 was abundant in bronchiolar lavage (BAL) even in naive mice; SOCS3 levels increased after administration of PGE 2 to the lungs and decreased after pulmonary delivery of LPS.Moreover, SOCS3 was retrieved from BAL from healthy human volunteers.Interestingly, exposure to cigarette smoke reduced levels of both SOCS1 and -3 in both mice and humans; so, smoking could lead to unchecked JAK-STAT activation, thereby contributing to inflammatory responses.Although it remains to be seen whether this particular form of epithelial-macrophage communication operates during respiratory infection, these data are important because they shed some light on the complex interactions that maintain homeostasis within the lung.It may be possible to exploit this system in order to down-regulate inflammation following infection and ultimately facilitate the restoration of immune homeostasis.
Phase I clinical investigation of amonafide.
Authors: R Saez, J B Craig, J G Kuhn, G R Weiss, J Koeller, J Phillips, K Havlin, G Harman, J Hardy, T J Melink
Journal: Journal of Clinical Oncology (1989)

Amonafide (benzisoquinolinedione, NSC 308847) is a new synthetic imide antineoplastic agent with DNA intercalative properties that has been evaluated in a phase I clinical trial. The drug was administered as a single intravenous (IV) infusion over 30 to 120 minutes repeated every 28 days. Ninety-five courses of therapy at doses ranging from 18 to 1,104 mg/m2 were administered to 38 patients with refractory solid tumors. Granulocytopenia was dose limiting. Leukopenia was seen in 13 of 31 courses at doses of 690 mg/m2 or greater. Life-threatening granulocytopenia (less than or equal to 250 microliters) was noted in 1/6 patients treated at 800 mg/m2, 1/8 patients treated at 918 mg/m2, and 2/5 patients treated at 1,104 mg/m2. No definite relationship between myelotoxicity and prior treatment status was noted. Rate-of-infusion dependent, nonhematologic toxicities included diaphoresis, flushing, dizziness, and tinnitus, all of which were ameliorated by increasing the duration of drug infusion to 120 minutes. In addition, nausea and vomiting (grades 1 and 2) were seen in 29/56 courses at doses greater than or equal to 519 mg/m2, but were easily controlled by phenothiazine antiemetics. Amonafide plasma and urine concentrations were determined by high-pressure liquid chromatography (HPLC). Plasma concentrations declined biexponetially with a terminal harmonic mean terminal half-life (t 1/2) of 5.5 h. The mean apparent volume of distribution at steady-state and total body clearance were 532 L/m2 and 84 L/h/m2, respectively. Less than 5% of the total dose of amonafide was excreted unchanged in the urine. Antitumor activity has been noted in one patient with non-small-cell lung cancer (one complete response exceeding 29 months duration) and in one patient with prostatic cancer (complete pain relief and improvement in bone scan for 9 months). The recommended dose for phase II trials with this schedule of amonafide is 918 mg/m2 with dose escalation to amonafide is 918 mg/m2 with dose escalation to myelotoxicity.
Elevated circulating levels of tumor necrosis factor predict unresponsiveness to treatment with interferon alfa-2b in chronic myelogenous leukemia.
Authors: F Herrmann, S G Helfrich, A Lindemann, E Schleiermacher, C Huber, R Mertelsmann
Journal: Journal of Clinical Oncology (1992)

PURPOSE The study was undertaken to analyze circulating tumor necrosis factor (TNF) levels in patients with chronic-phase chronic myelogenous leukemia (CML) undergoing interferon (IFN) alfa-2b therapy, and to correlate pretreatment serum levels of TNF with response to IFN alfa-2b therapy. PATIENTS AND METHODS Fourteen patients with CML in chronic phase were treated with recombinant human IFN alfa-2b for 7 to 39 months. RESULTS In eight patients IFN alfa-2b treatment failed due to lack of hematologic response. A complete or partial hematologic remission was achieved in the remaining six patients, of whom two patients experienced a complete cytogenetic response. Retrospective analysis of serum samples obtained from all patients before the onset of IFN alfa-2b administration revealed that levels (mean +/- SEM) of circulating TNF were higher (P less than .001) in the group of patients who did not respond to IFN alfa-2b treatment (157 +/- 15 U/mL) than in the responders (10.3 +/- 4 U/mL) or healthy control subjects (9.1 +/- 3 U/mL). However, there was no correlation between TNF serum levels and other patient characteristics at study enrollment including age, sex, duration of disease, performance status, splenomegaly, WBC count, platelet count, hemoglobin value, prior therapy, and prognostic category. CONCLUSION These findings indicate that circulating levels of TNF are increased in a subset of patients with chronic-phase CML and that this elevation is associated with poor response to IFN alfa-2b therapy.
Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin.
Authors: M Markman, B Reichman, T Hakes, W Jones, J L Lewis, S Rubin, L Almadrones, W Hoskins
Journal: Journal of Clinical Oncology (1991)

Phase II trials of second-line intraperitoneal (IP) cisplatin-based therapy in patients with ovarian cancer have demonstrated the ability of this approach to produce objective antitumor responses, including surgically defined complete responses (CRs), in individuals with persistent small-volume disease after front-line cisplatin-based intravenous (IV) treatment. To examine the influence of a prior response to systemic cisplatin on the activity of second-line IP cisplatin, we retrospectively analyzed two phase II trials of cisplatin-based IP therapy in persistent/recurrent ovarian cancer conducted at our institution. Of the 89 assessable patients on the two trials, 52 (58%) had previously responded to IV cisplatin. The overall response and CR rates to second-line IP cisplatin-based therapy in this previously responding population were 56% and 33%, respectively, compared with overall response and CR rates in the 37 nonresponders to IV cisplatin of 11% and 3%, respectively (P less than .001; chi 2, 1 df). In the 36 patients responding to systemic cisplatin and whose largest tumor mass measured less than 1 cm at IP cisplatin initiation, a 42% CR rate was observed, compared with a 7% CR rate in the 14 patients with the same bulk of disease who had previously failed to respond to systemic cisplatin (P less than .025). We conclude that a prior response to systemic cisplatin strongly influences the antineoplastic activity of second-line IP cisplatin in ovarian cancer.
Percutaneous Implantation of an Entirely Intracardiac Leadless Pacemaker
Authors: Vivek Y. Reddy, Derek V. Exner, Daniel J. Cantillon, Rahul Doshi, T. Jared Bunch, Gery F. Tomassoni, Paul A. Friedman, N.A. Mark Estes, John Ip, Imran Niazi, Kenneth Plunkitt, Rajesh Banker, James Porterfield, James E. Ip, Srinivas R. Dukkipati
Journal: New England Journal of Medicine (2015)

Cardiac pacemakers are limited by device-related complications, notably infection and problems related to pacemaker leads. We studied a miniaturized, fully self-contained leadless pacemaker that is nonsurgically implanted in the right ventricle with the use of a catheter.In this multicenter study, we implanted an active-fixation leadless cardiac pacemaker in patients who required permanent single-chamber ventricular pacing. The primary efficacy end point was both an acceptable pacing threshold (≤2.0 V at 0.4 msec) and an acceptable sensing amplitude (R wave ≥5.0 mV, or a value equal to or greater than the value at implantation) through 6 months. The primary safety end point was freedom from device-related serious adverse events through 6 months. In this ongoing study, the prespecified analysis of the primary end points was performed on data from the first 300 patients who completed 6 months of follow-up (primary cohort). The rates of the efficacy end point and safety end point were compared with performance goals (based on historical data) of 85% and 86%, respectively. Additional outcomes were assessed in all 526 patients who were enrolled as of June 2015 (the total cohort).The leadless pacemaker was successfully implanted in 504 of the 526 patients in the total cohort (95.8%). The intention-to-treat primary efficacy end point was met in 270 of the 300 patients in the primary cohort (90.0%; 95% confidence interval [CI], 86.0 to 93.2, P=0.007), and the primary safety end point was met in 280 of the 300 patients (93.3%; 95% CI, 89.9 to 95.9; P<0.001). At 6 months, device-related serious adverse events were observed in 6.7% of the patients; events included device dislodgement with percutaneous retrieval (in 1.7%), cardiac perforation (in 1.3%), and pacing-threshold elevation requiring percutaneous retrieval and device replacement (in 1.3%).The leadless cardiac pacemaker met prespecified pacing and sensing requirements in the large majority of patients. Device-related serious adverse events occurred in approximately 1 in 15 patients. (Funded by St. Jude Medical; LEADLESS II ClinicalTrials.gov number, NCT02030418.).
Abstract 14297: Hypothalamic Activation Due to Ccl2 Causes Stress (takotsubo) Cardiomyopathy via Upregulation of Neuropeptide Y in the Cardiac Sympathetic Nerves
Authors: Takahide Arai, Kensuke Kimura, Masaki Ieda, Hiroyuki Yamakawa, Shinsuke Yuasa, Keiichi Fukuda
Journal: Circulation (2012)
Association of Google Search Volume Index Peaks for Skin Cancer With Skin Cancer Awareness Month—Reply
Authors: Kyle T. Amber, Romi Bloom, Shasa Hu
Journal: JAMA Dermatology (2016)

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Opportunities for the Cardiovascular Community in the Precision Medicine Initiative
Authors: Svati H. Shah, Donna Arnett, Steven R. Houser, Geoffrey S. Ginsburg, Calum MacRae, Seema Mital, Joseph Loscalzo, Jennifer L. Hall
Journal: Circulation (2016)

The Precision Medicine Initiative recently announced by President Barack Obama seeks to move the field of precision medicine more rapidly into clinical care. Precision medicine revolves around the concept of integrating individual-level data including genomics, biomarkers, lifestyle and other environmental factors, wearable device physiological data, and information from electronic health records to ultimately provide better clinical care to individual patients. The Precision Medicine Initiative as currently structured will primarily fund efforts in cancer genomics with longer-term goals of advancing precision medicine to all areas of health, and will be supported through creation of a 1 million person cohort study across the United States. This focused effort on precision medicine provides scientists, clinicians, and patients within the cardiovascular community an opportunity to work together boldly to advance clinical care; the community needs to be aware and engaged in the process as it progresses. This article provides a framework for potential involvement of the cardiovascular community in the Precision Medicine Initiative, while highlighting significant challenges for its successful implementation.
Evaluation and Management of the Unknown Primary Carcinoma of the Head and Neck
Authors: Chad E. Galer, Merrill S. Kies
Journal: Journal of the National Comprehensive Cancer Network (2008)

Squamous cell carcinoma of unknown primary origin in the head and neck is encountered as a recurring clinical problem in head and neck cancer clinics, affecting 3% to 25% of patients. This article describes the clinical presentation, appropriate evaluation, and treatment strategies for this important subgroup. Treatment—best carried out with multidisciplinary teams of specialists experienced in the care of head and neck cancer patients—is curative for most of these patients.
Human hematopoietic stem cells from mobilized peripheral blood can be purified based on CD49f integrin expression
Authors: Heather D. Huntsman, Taha Bat, Hai Cheng, Ayla Cash, Patali S. Cheruku, Jian-Fei Fu, Keyvan Keyvanfar, Richard W. Childs, Cynthia E. Dunbar, Andre Larochelle
Journal: Blood (2015)