tbuckley/cabot-search huggingface dataset:
Results of Genoidentical Hemopoietic Stem Cell Transplantation With Reduced Intensity Conditioning for Acute Myelocytic Leukemia: Higher Doses of Stem Cells Infused Benefit Patients Receiving Transplants in Second Remission or Beyond—The Acute Leukemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation
Authors: Norbert-Claude Gorin, Myriam Labopin, Jean-Michel Boiron, Niklas Theorin, Tim Littlewood, Shimon Slavin, Hildegard Greinix, Jean Yves Cahn, E. Paolo Alessandrino, Alessandro Rambaldi, Arnon Nagler, Emmanuelle Polge, Vanderson Rocha
Journal: Journal of Clinical Oncology (2006)

Purpose Nucleated cell dose is an important and modifiable factor in hematopoietic stem cell transplantation (HSCT), however its association with outcomes in the context of reduced intensity conditioning regimen (RIC) HSCT for adults with acute myelocytic leukemia (AML) is not known. Patients and Methods From 1998 to 2003, 253 patients with de novo AML, received transplants with RIC and peripheral blood from a genoidentical donor. Median age was 55 years (range, 18 to 72) and the median follow-up was 17 months (range, 2 to 67). One hundred forty one patients received transplants in first remission (CR1), 47 received transplants in second remission (CR2), and 65 patients received transplants in a more advanced phase. Fludarabin-based RIC was used in 91% of patients and low-dose (&lt; 4 Gy) total-body radiation in 23% of patients. The median nucleated and CD34 cell dose infused were 9.1× 10 8 /kg and 5.8× 10 6 /kg, respectively. Results Overall, 2-year leukemia-free survival (LFS) was 41% ± 4% and it was 46% ± 5% for patients receiving a higher cell dose (&gt; 9.1× 10 8 /kg) and 37% ± 5% for the remainders (P = .03). Higher cell doses exclusively benefited patients who received transplantations in CR2 or beyond, with LFS of 47 ± 8 versus 20 ± 8, with no detectable effect for patients who received transplants in CR1. In a multivariate analysis of the overall patient population, higher nucleated cell dose cells were associated with higher LFS (P = .04), higher incidence of chronic graft-versus-host disease (P = .01), and there was a trend towards a lower relapse incidence (P = .06). Interestingly, CD34+ cell dose was not associated with any outcomes. Conclusion Nucleated cell dose is an important factor that can be modified to improve results of RIC for patients with AML transplanted later than in CR1.
Coxsackievirus B Epidemic at a Boys' Summer Camp
Authors: H. Bradford Hawley
Journal: JAMA (1973)

During an outbreak of coxsackievirus B5 at a boys' summer camp located on Lake Champlain, virus was successfully isolated for the first time (to our knowledge) from a large body of recreational water. This was accomplished by using polyelectrolyte 60 to concentrate the virus. Polyelectrolyte 60 was also used in the isolation of viruses from clinical specimens obtained from campers and staff who had a wide variety of clinical syndromes. Virus present in lake swimming water may play an important role in some enterovirus outbreaks.
The AP-1 repressor protein, JDP2, potentiates hepatocellular carcinoma in mice
Authors: Keren Bitton-Worms, Eli Pikarsky, Ami Aronheim
Journal: Molecular Cancer (2010)

Abstract Background The AP-1 transcription factor plays a major role in cell proliferation, apoptosis, differentiation and developmental processes. AP-1 proteins are primarily considered to be oncogenic. Gene disruption studies placed c-Jun as an oncogene at the early stage of a mouse model of hepatocellular carcinoma. Mice lacking c-Jun display reduced number and size of hepatic tumors attributed to elevated p53 expression and increased apoptosis. This suggests that c-Jun inhibition may serve as a therapeutic target for liver cancer. The c-Jun dimerization protein 2, JDP2 is an AP-1 repressor protein that potently inhibits AP-1 transcription. On the other hand, the JDP2 locus was found at a recurring viral integration site in T-cell lymphoma. We sought to examine the potential of JDP2 to inhibit c-Jun/AP-1 oncogenic activity in mice. Towards this end, we generated a tetracycline inducible transgenic mouse expressing JDP2 specifically in the liver. We used diethylnitrosamine (DEN) injection to initiate liver cancer in mice and assessed the extent of liver cancer in JDP2-transgenic and wild type control mice by biochemical and molecular biology techniques. Results JDP2-transgenic mice display normal liver function. JDP2-transgenic mice displayed potentiation of liver cancer, higher mortality and increased number and size of tumors. The expression of JDP2 at the promotion stage was found to be the most critical for enhancing liver cancer severity. Conclusions This study suggests that JDP2 expression may play a critical role in liver cancer development by potentiating the compensatory proliferative response and increased inflammation in the DEN liver cancer model.
Reduction in tissue iron stores with a new regimen of continuous ambulatory intravenous deferoxamine
Authors: Nancy F. Olivieri, Susan A. Davis, Peter P. Liu, Ann Marie Berriman, Beverley J. Tyler, William H. Francombe
Journal: American Journal of Hematology (1992)

Abstract A new regimen of 24‐hr ambulatory continuous intravenous infusion of deferoxamine (CIV OFO) through central venous ports was instituted in nine patients aged (mean ± SD) 22.4 ± 5.8 years over a period of 15.7 ± 7.3 months. Central venous infusion sites were changed weekly in the clinic, eliminating the necessity for reconstitution of DFO and needle Insertion at home. Because CIV DFO could be interrupted only by medical personnel, patient compliance was documented accurately; patients administered 93.0% ± 3.2% of CIV DFO prescribed. Mean urinary iron excretion on CIV DFO (66.8 ± 50.4 mg/24 hr) was significantly greater than that quantitated during 12‐hr equivalent‐dose subcutaneous DFO infusions (23.4 ± 18.3 mg/24 hr; P &lt; 0.025). Mean serum ferritin declined by 71% over the treatment period ( P &lt; 0.005). This regimen confers the advantages of uninterrupted exposure to DFO, is associated with excellent patient compliance, and should be considered in any patient with severe iron overload and erratic compliance with DFO. © 1992 Wiley‐Liss, Inc.
Defibrillation Efficacy of Commercially Available Biphasic Impulses in Humans
Authors: Gery Tomassoni, Keith Newby, Sanjay Deshpande, Kathi Axtell, Jasbir Sra, Masood Akhtar, Andrea Natale
Journal: Circulation (1997)

Background Recent studies have shown that specifically shaped biphasic waveforms can lower energy requirements for ventricular defibrillation. We prospectively compared the defibrillation efficacy of three different biphasic wave shapes incorporated in three commercially available implantable defibrillators. The results led to the development of a second protocol in which the importance of negative-phase peak voltage and duration was investigated. Methods and Results Defibrillation threshold (DFT) testing using different biphasic waveforms was performed randomly on 42 patients undergoing implantation of a cardioverter-defibrillator for ventricular arrhythmias. In 23 patients (group 1), 3 waveforms were tested: a CPI waveform with 60% positive-phase (P1) tilt and 50% negative-phase (P2) tilt, a Medtronic waveform with 65% fixed tilt in both P1 and P2, and a Ventritex waveform with 60% P1 tilt and a P2 leading edge voltage equal to half of the P1 trailing edge voltage. In 19 patients (group 2), 3 biphasic waveforms with equal P1 tilt at 65% but shorter P2 duration or smaller P2 peak voltage were tested. The Endotak C 60 series lead system (CPI) was used in 11 patients in group 1 and 10 patients in group 2. A Transvene lead system (Medtronics) was used in the remaining patients. Stored energy required for defibrillation was significantly lower with the CPI waveform compared with the Ventritex waveform. In group 2, energy requirements were significantly increased for the waveform with a smaller P2 peak voltage, whereas a short P2 duration did not influence defibrillation success. Conclusions Our results suggest that specifically shaped biphasic waveforms delivered from commercially available devices can affect energy requirements for defibrillation. More importantly, the amplitude of the P2 peak voltage may be a more critical determinant than the P2 duration for defibrillation success of biphasic waveforms in humans.
The Early and Late Phases of Ischemic Preconditioning
Authors: Yumin Qiu, Xian-Liang Tang, Seong-Wook Park, Jiang-Zhong Sun, Anantharam Kalya, Roberto Bolli
Journal: Circulation Research (1997)

Abstract The effectiveness of the late phase of ischemic preconditioning (PC) in protecting against myocardial infarction and the concomitant contractile dysfunction after sustained ischemia remains unclear. The early and late phases of PC have not been compared using the same protocol in the same experimental model; furthermore, the late phase of PC has not been assessed in the conscious state in a large animal preparation. The goal of this study was to directly compare the effects of early and late PC on myocardial infarct size and postischemic dysfunction in chronically instrumented, conscious pigs. Four groups of pigs were subjected to a 40-minute coronary occlusion followed by 3 days of reperfusion. Group 1 (n=7) served as control. Group 2 (n=6) was subjected to ten 2-minute occlusion/2-minute reperfusion cycles 25 minutes before the 40-minute occlusion (early PC). Groups 3 (n=7) and 4 (n=4) were subjected to 10 and 25 cycles, respectively, of 2-minute occlusion/2-minute reperfusion 24 hours before the 40-minute occlusion (late PC). Infarct size averaged 45.1±5.9% of the region at risk in control pigs, was reduced by 79% (to 9.4±3.2%) in group 2, but did not differ in groups 3 (33.3±4.8%) and 4 (38.8±8.2%) versus group 1. Power analysis demonstrated that there was an 80% probability of detecting a 40% decrease in infarct size in groups 3 and 4 versus group 1. The recovery of systolic wall thickening (measured with ultrasonic crystals) after the 40-minute occlusion was poor in groups 1, 3, and 4 but markedly enhanced in group 2 throughout the 3 days of reperfusion; this beneficial effect could have been due to limitation of infarct size, alleviation of stunning, or both. Thus, a series of ten 2-minute coronary occlusions had a profound (≈80%) early infarct–limiting effect, which was associated with a marked functional benefit. This protection, however, disappeared 24 hours later and could not be reinstituted by increasing the number of PC coronary occlusions to 25. The incidence and duration of ventricular tachycardia after reperfusion was not changed by either early or late PC; no conclusions could be drawn regarding ventricular fibrillation or ischemia-induced ventricular tachycardia, since these arrhythmias did not occur in control animals. Taken together, the present results demonstrate striking differences between the early and late effects of PC: In conscious swine subjected to a sustained coronary occlusion, a PC protocol that induces powerful protection during the early phase of PC fails to induce any protection during the late phase, indicating either that a late protective effect of PC does not exist or that, if it exists, it must be weaker than the early protective effect.
Accurate Assessment of Aortic Stenosis
Authors: Neelakantan Saikrishnan, Gautam Kumar, Fadi J. Sawaya, Stamatios Lerakis, Ajit P. Yoganathan
Journal: Circulation (2014)

may also be used, depending on the indications from transthoracic echocardiography .The following sections describe the use of various modalities used to diagnose AS.Table 1 summarizes some key advantages and disadvantages of using various modalities in the diagnosis of AS.
Augmenting Chemosensitivity of Malignant Melanoma Tumors via Proteasome Inhibition
Authors: Katayoun I. Amiri, Linda W. Horton, Bonnie J. LaFleur, Jeffrey A. Sosman, Ann Richmond
Journal: Cancer Research (2004)

Abstract Melanoma poses a great challenge to patients, oncologists, and biologists because of its nearly universal resistance to chemotherapy. Many studies have shown that nuclear factor κB is constitutively activated in melanoma, thereby promoting the proliferation of melanoma cells by inhibiting the apoptotic responses to chemotherapy. Nuclear factor κB activity is regulated by phosphorylation and subsequent degradation of inhibitor of nuclear factor κB by the ubiquitin-proteasome pathway. In this study, we show that the novel proteasome inhibitor, bortezomib, inhibited the growth of melanoma cells in vitro at a concentration range of 0.1–10 nm and in combination with the chemotherapeutic agent temozolomide, the inhibitory effect on melanoma cell growth was even more prominent. Data from a murine model showed reduced tumor growth when bortezomib was administered to human melanoma tumors. Strikingly, animals receiving bortezomib in combination with temozolomide achieved complete remission of palpable tumors after only 30 days of therapy, lasting &amp;gt;200 days. Our data indicate strongly that bortezomib in combination with chemotherapeutic agents should be studied additionally for the treatment of melanoma.
LAP+CD4+ T Cells Are Suppressors Accumulated in the Tumor Sites and Associated with the Progression of Colorectal Cancer
Authors: Jayashri Mahalingam, Yung-Chang Lin, Jy-Ming Chiang, Po-Jung Su, Jian-He Fang, Yu-Yi Chu, Ching-Tai Huang, Cheng-Tang Chiu, Chun-Yen Lin
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Suppressor T cells are one of the determinants of colorectal cancer (CRC) clinical outcome. LAP+CD4+ T cell is a recently identified subset of suppressor T cells. This study was designed to investigate their clinical relevance in patients with CRC. Experimental Design: Sixty patients with CRC and 24 healthy donors (HD) were enrolled in this study. The percentages of LAP+CD4+ T cells in peripheral blood and tumor tissue were measured. The phenotype and functional relevance of LAP+CD4+ T cells were analyzed subsequently. Results: The percentages of LAP+CD4+ T cells in peripheral blood of patients with CRC were significantly higher than HD (HD vs. CRC: 3.1% ± 0.78% vs. 8.8% ± 5.8%, P &amp;lt; 0.0001) and in tumor tissue when compared with nontumor tissue (nontumor vs. tumor: 3.2% ± 1.1% vs. 9.5% ± 5.5%, P = 0.0002). In addition, LAP+CD4+ T cells with effector memory (EM) phenotype were more likely to accumulate in the tumor sites than in peripheral blood. These LAP+CD4+ T cells produced significantly higher levels of IFN-γ, IL-17 and comparatively lower IL-2 and very few IL-10. LAP+CD4+ T cells could suppress the proliferation of LAP−CD4+ T cells that were partially mediated by TGF-β. Furthermore, these LAP+CD4+ T cells accumulated in tumor site and increased further in the peripheral blood in patients with metastasis. Conclusions: LAP+CD4+ T cells as a suppressor subset could accumulate in the tumor microenvironment and circulated more in the peripheral blood with tumor progression in patients with CRC. Clin Cancer Res; 18(19); 5224–33. ©2012 AACR.
Intravenous silibinin monotherapy shows significant antiviral activity in HCV-infected patients in the peri-transplantation period
Authors: Zoe Mariño, Gonzalo Crespo, Massimo D’Amato, Nadia Brambilla, Giampaolo Giacovelli, Lucio Rovati, Josep Costa, Miquel Navasa, Xavier Forns
Journal: Journal of Hepatology (2012)
Efficacy of Psyllium in Reducing Serum Cholesterol Levels in Hypercholesterolemic Patients on High- or Low-Fat Diets
Authors: Dennis L. Sprecher
Journal: Annals of Internal Medicine (1993)

Objectives: To determine the efficacy of psyllium in reducing serum cholesterol levels in patients on high- or low-fat diets. Design: Double-blind, placebo-controlled, 16-week parallel trial. The study included an 8-week baseline period and an 8-week treatment period. Patients: Healthy men and women, 21 to 70 years old, with primary hypercholesterolemia (total serum cholesterol 5.7 mmol/L [220 mg/dL]). Thirty-seven participants followed a high-fat diet and 81 participants followed a low-fat diet. Intervention: Participants were randomly assigned to either psyllium, 5.1 g twice a day, or placebo. Measurements: Fasting lipid and apolipoprotein concentrations, including direct low-density lipoprotein (LDL) cholesterol quantification; nutritional analyses of 4 days of 7-day food records to monitor dietary compliance; and physical examinations, clinical chemistry and hematologic studies, and urinalysis to assess treatment safety. Main Results: Psyllium recipients in both the high- and low-fat diet groups showed small but significant decreases (P < 0.05) in total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Total cholesterol and LDL cholesterol levels decreased 5.8% and 7.2%, respectively, in psyllium recipients on high-fat diets and 4.2% and 6.4%, respectively, in psyllium recipients on low-fat diets. No significant difference was seen in LDL cholesterol response when psyllium recipients on low- and high-fat diets were compared (P > 0.2). No significant reductions in lipid levels were observed in placebo recipients. Based on the National Cholesterol Education Program LDL cholesterol classification system, 39% of the psyllium recipients improved in LDL cholesterol classification (P < 0.0001) compared with 20.3% of placebo recipients (P > 0.2). Conclusions: Psyllium produces a modest but significant improvement in total cholesterol and LDL cholesterol levels in persons on either low-fat or high-fat diets. Psyllium, when added to a prescribed low-fat diet, may obviate the need for typical lipid-lowering medications or may prove to be a valuable adjunct to other treatments in patients with moderately elevated LDL cholesterol levels.
A radioisotope method of measuring intragastric volumes using the Volemetron
Authors: R. A. Hinder, C. G. Bremner
Journal: Gut (1973)

A new method of measuring intragastric volumes using the Volémetron and <sup>125</sup>RIHSA is reported. The method has been used to measure serially the change in intragastric volumes following milk and water feeds in a group of six dogs.
Acute Hemodynamic Benefits of Bi-Atrial Atrioventricular Sequential Pacing With the Optimal Atrioventricular Delay
Authors: Atsushi Doi, Masahiko Takagi, Iku Toda, Minoru Yoshiyama, Kazuhide Takeuchi, Junichi Yoshikawa
Journal: Journal of the American College of Cardiology (2005)
Spontaneous hypoglycaemia due to a pleural fibroma: role of insulin like growth factors.
Authors: E A Masson, I A MacFarlane, D Graham, P Foy
Journal: Thorax (1991)

A 64 year old woman with a long history of "drop attacks" and dizzy spells was found to have spontaneous hypoglycaemia. A slowly enlarging pleural mass had been present for at least five years. At thoracotomy the mass (weight 1.7 kg) was excised and the hypoglycaemia ceased. Histologically the tumour was a pleural fibroma, with no features of malignancy. Endocrine tests before surgery showed a subnormal growth hormone response to spontaneous hypoglycaemia, a reduced concentration of serum insulin like growth factor I (IGF-I), and an inappropriately high concentration of serum insulin like growth factor II (IGF-II). After resection of the tumour the growth hormone response to insulin induced hypoglycaemia and the IGF-I and IGF-II concentrations were normal. These data suggest that the hypoglycaemia was due to production of IGF-II by the tumour, causing increased glucose utilisation and an impaired growth hormone counterregulatory response to hypoglycaemia.
Sulfur as a Signaling Nutrient Through Hydrogen Sulfide
Authors: Omer Kabil, Victor Vitvitsky, Ruma Banerjee
Journal: Annual Review of Nutrition (2014)

Hydrogen sulfide (H 2 S) has emerged as an important signaling molecule with beneficial effects on various cellular processes affecting, for example, cardiovascular and neurological functions. The physiological importance of H 2 S is motivating efforts to develop strategies for modulating its levels. However, advancement in the field of H 2 S-based therapeutics is hampered by fundamental gaps in our knowledge of how H 2 S is regulated, its mechanism of action, and its molecular targets. This review provides an overview of sulfur metabolism; describes recent progress that has shed light on the mechanism of H 2 S as a signaling molecule; and examines nutritional regulation of sulfur metabolism, which pertains to health and disease.
Gene Expression Profiling of the Forming Atrioventricular Node Using a Novel <i>Tbx3</i> -Based Node-Specific Transgenic Reporter
Authors: Thomas Horsthuis, Henk P.J. Buermans, Janynke F. Brons, Arie O. Verkerk, Martijn L. Bakker, Vincent Wakker, Danielle E.W. Clout, Antoon F.M. Moorman, Peter A.C. 't Hoen, Vincent M. Christoffels
Journal: Circulation Research (2009)

The atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV nodal myocardium-specific reporter mouse to gain insight into the gene programs determining the formation and phenotype of the developing AV node. In this reporter, green fluorescent protein (GFP) expression was driven by a 160-kbp bacterial artificial chromosome with Tbx3 and flanking sequences. GFP was selectively active in the AV canal of embryos and AV node of adults, whereas the Tbx3-positive AV bundle and sinus node were devoid of GFP, demonstrating that distinct regulatory sequences and pathways control expression in the components of the conduction system. Fluorescent AV nodal and complementary Nppa-positive chamber myocardial cell populations of embryonic day 10.5 embryos and of embryonic day 17.5 fetuses were purified using fluorescence-activated cell sorting, and their expression profiles were assessed by genome-wide microarray analysis, providing valuable information concerning their molecular identities. We constructed a comprehensive list of sodium, calcium, and potassium channel genes specific for developing nodal or chamber myocardium. Furthermore, the data revealed that the AV node and the chamber (working) myocardium phenotypes diverge during development but that the functional gene classes characterizing both subtypes are maintained. One of the repertoires identified in the AV node-specific gene profiles consists of multiple neurotrophic factors and semaphorins, not yet appreciated to play a role in nodal development, revealing shared characteristics between nodal and nervous system development.