tbuckley/cabot-search huggingface dataset:
Abstract 1808: Duffy Antigen Receptor for Chemokines (Darc) Polymorphism Regulates Circulating Concentrations of Monocyte Chemoattractant Protein-1 and Other Circulating Inflammatory Mediators
Authors: Renate B. Schnabel, Jens Baumert, Maja Barbalic, Patrick T. Ellinor, Peter Durda, Abbas Dehghan, Joshua C. Bis, Thomas Illig, Alanna C. Morrison, Nancy S. Jenny, John F. Keaney, Christian Gieger, Cathy Tilley, Jennifer F. Yamamoto, Natalie Khuseyinova, Gerardo Heiss, Margaret Doyle, Stefan Blankenberg, Christian Herder, Jeremy D. Walston, Yanyan Zhu, Ramachandran S. Vasan, Norman Klopp, Eric Boerwinkle, Martin G. Larson, Bruce M. Psaty, Annette Peters, Christie M. Ballantyne, Jacqueline C. M. Witteman, Ron C. Hoogeveen, Emelia J. Benjamin, Wolfgang Koenig, Russell P. Tracy
Journal: Circulation (2009)

Background: Monocyte chemoattractant protein (MCP)-1 is a cytokine central to the inflammatory process. The genetics of MCP-1 are little understood. Methods and Results: To identify the genetic bas...
Single-Injection Depot Progesterone Before Surgery and Survival in Women With Operable Breast Cancer: A Randomized Controlled Trial
Authors: Rajendra Badwe, Rohini Hawaldar, Vani Parmar, Mandar Nadkarni, Tanuja Shet, Sangeeta Desai, Sudeep Gupta, Rakesh Jalali, Vaibhav Vanmali, Rajesh Dikshit, Indraneel Mittra
Journal: Journal of Clinical Oncology (2011)

Many nonrandomized studies have suggested better outcome for patients with breast cancer who undergo surgery during the luteal (progestogenic) phase of their menstrual cycle, but this is controversial. We investigated the effect of a single preoperative injection of hydroxyprogesterone in women with operable breast cancer (OBC) in a randomized controlled trial (ClinicalTrials.gov identifier, NCT00123669).One thousand patients with OBC were randomly assigned to receive surgery or an intramuscular injection of depot hydroxyprogesterone 500 mg 5 to 14 days before surgery. Primary and secondary end points were disease-free survival (DFS) and overall survival (OS), respectively. An analysis by axillary lymph node status was preplanned.At a median follow-up of 65 months among 976 eligible patients, 273 recurrences and 202 deaths were recorded. In the progesterone group versus control group, 5-year DFS and OS rates were 73.9% v 70.2% (hazard ratio [HR], 0.87; 95% CI, 0.68 to 1.09; P = .23) and 80.2% v 78.4% (HR, 0.92; 95% CI, 0.69 to 1.21; P = .53), respectively. In 471 node-positive patients, the 5-year DFS and OS rates in the progesterone group versus control group were 65.3% v 54.7% (HR, 0.72; 95% CI, 0.54 to 0.97; P = .02) and 75.7% v 66.8% (HR, 0.70; 95% CI, 0.49 to 0.99; P = .04), respectively. In multivariate analysis, DFS was significantly improved with progesterone in node-positive patients (adjusted HR, 0.71; 95% CI, 0.53 to 0.95; P = .02), whereas there was no significant effect in node-negative patients (P for interaction = .04).A single injection of hydroxyprogesterone before surgery did not improve outcomes in all women with OBC. This intervention showed significant improvement in node-positive women that may be considered hypothesis generating. If replicated in other studies, this could be a simple and inexpensive intervention, especially in developing countries where the incidence of lymph node metastasis is high.
Properties and Malignant Transformation of Established Rat Liver Parenchymal Cells in Culture<xref ref-type="fn" rid="fn2">2</xref>
Authors: E Borenfreund, P J Higgins, M Steinglass, A Bendich
Journal: JNCI Journal of the National Cancer Institute (1975)

Epithelioid cells from the livers of normal and genetically impaired (Gunn) rats were established in long-term cultures in vitro. These cells grew as flat, epithelioid cobble-stone-type monolayers and showed a diploid karyotype. They secreted rat serum albumin and proteins into their growth media and contained aryl hydrocarbon hydroxylase. Such cells were transformed by treatment with methylazoxymethanol acetate; they then exhibited an irregular, piling growth pattern, acquired the ability to grow in soft agar, and thereafter grew as tumors in hamsters given cortisone and in nude mice. These malignant spindle-cell tumors were reestablished in culture and still secreted serum albumin. The transformed cells became highly multinucleate when exposed to cytochalasin B and thus behaved like tumor cells. This behavior was not shown by the original cells. Cells transformed by benzo[a]pyrene failed to grow in soft agar culture or as tumor in animals. Cells were not affected by diethylnitrosamine.
Can Dementia Be Prevented? Brain Aging in a Population-Based Context
Authors: Mary N. Haan, Robert Wallace
Journal: Annual Review of Public Health (2004)

As a consequence of global aging of the human population, the occurrence of cognitive impairment and dementia is rapidly becoming a significant burden for medical care and public health systems. By the year 2020, the WHO predicts there will be nearly 29 million demented people in both developed and developing countries. Primary and secondary prevention of dementia through individual and population-level interventions could reduce this imminent risk. Vascular risk factors such as type 2 diabetes, hypertension, dietary fat intake, high cholesterol, and obesity have emerged as important influences on the risk of both vascular and Alzheimer's dementia. Understanding the reasons for differences between populations in genetic vulnerability and environmental exposures may help to identify modifiable risk factors that may lead to effective prevention of vascular and Alzheimer's dementia.
Increasing Varenicline Dose in Smokers Who Do Not Respond to the Standard Dosage
Authors: Peter Hajek, Hayden McRobbie, Katherine Myers Smith, Anna Phillips, Danielle Cornwall, Al-Rehan Dhanji
Journal: JAMA Internal Medicine (2014)

Standard varenicline tartrate dosing was formulated to avoid adverse effects (primarily nausea), but some patients may be underdosed. To our knowledge, no evidence-based guidance exists for physicians considering increasing varenicline dose if there is no response to the standard dosage.To determine whether increasing varenicline dose in patients showing no response to the standard dosage improves treatment efficacy.In a double-blind randomized placebo-controlled trial, 503 smokers attending a stop smoking clinic commenced varenicline use 3 weeks before their target quit date (TQD). Two hundred participants reporting no strong nausea, no clear reduction in smoking enjoyment, and less than 50% reduction in their baseline smoking on day 12 received additional tablets of varenicline or placebo.All participants began standard varenicline tartrate dosing, gradually increasing to 2 mg/d. Dose increases of twice-daily varenicline (0.5 mg) or placebo took place on days 12, 15, and 18 (up to a maximum of 5 mg/d).Participants rated their smoking enjoyment during the prequit period and withdrawal symptoms weekly for the first 4 weeks after the TQD. Continuous validated abstinence rates were assessed at 1, 4, and 12 weeks after the TQD.The dose increase reduced smoking enjoyment during the prequit period, with mean (SD) ratings of 1.7 (0.8) for varenicline vs 2.1 (0.7) for placebo (P = .001). It had no effect on the mean (SD) frequency of urges to smoke at 1 week after the TQD, their strength, or the severity of withdrawal symptoms: these ratings for varenicline vs placebo were 2.7 (1.1) vs 2.6 (0.9) (P = .90), 2.6 (1.1) vs 2.8 (1.0) (P = .36), and 1.5 (0.4) vs 1.6 (0.5) (P = .30), respectively. The dose increase also had no effect on smoking cessation rates for varenicline vs placebo at 1 week (37 [37.0%] vs 48 [48.0%], P = .14), 4 weeks (51 [51.0%] vs 59 [59.0%], P = .32), and 12 weeks (26 [26.0%] vs 23 [23.0%], P = .61) after the TQD. There was significantly more nausea (P < .001) and vomiting (P < .001) reported in the varenicline arm than in the placebo arm.Increasing varenicline dose in smokers with low response to the drug had no significant effect on tobacco withdrawal symptoms or smoking cessation. Physicians often consider increasing the medication dose if there is no response to the standard dosage. This approach may not work with varenicline.clinicaltrials.gov Identifier: NCT01206010.
Does external ultrasound accelerate thrombolysis? Results from a rabbit model.
Authors: R Kornowski, R S Meltzer, A Chernine, Z Vered, A Battler
Journal: Circulation (1994)

BACKGROUND Prior in vitro and in vivo studies have reported that external ultrasound accelerates thrombolysis at intensities too low to have a direct effect on clot dissolution in the absence of a thrombolytic agent. The present study was undertaken to examine the ultrasound effect on thrombolysis and reocclusion in a rabbit thrombosis model. METHODS AND RESULTS Blood clots were produced in a femoral artery segment with endothelial damage and distal stenosis. Recombinant tissue-type plasminogen activator (rTPA) was infused at 30 micrograms.kg-1.min-1 for 60 minutes. Femoral artery flow was measured every 5 minutes for 2 hours. Rabbits were randomized to four groups with continuous wave ultrasound on or off with or without intravenous injection of 17 mg/kg aspirin (+US/-US/+Asp/-Asp). Ultrasound frequency and intensity were 1 MHz and 6.3 W/cm2. In seven of eight and five of five rabbits given rTPA and -US/-Asp or -US/+Asp, respectively, reflow was observed, persisting to the end of the observation period. In five of nine and four of five rabbits given rTPA and +US/-Asp or +US/+Asp, reflow was achieved, but persistent reocclusion was subsequently observed in five of five and two of four of these rabbits, respectively. Overall, femoral artery patency was worse and reocclusion occurred more often when ultrasound was added to rTPA (P = .002 by nonparametric ANOVA). However, initial reflow occurred more rapidly with ultrasound exposure (21 +/- 10 and 33 +/- 6 minutes for the +US/+Asp and +US/-Asp groups, respectively) compared with without ultrasound (46 +/- 13 and 74 +/- 14 minutes for the -US/+Asp and -US/-Asp groups, respectively) (P = .03 by ANOVA). CONCLUSIONS Although time to initial reflow was shortened by ultrasound, it was associated with less reperfusion and more reocclusion in this model. A possible explanation for these results is ultrasound-induced platelet activation counterbalancing its thrombolysis-accelerating effect.
Opposing Effects of Transmembrane and Soluble FAS Ligand Expression on Inflammation and Tumor Cell Survival
Authors: Andreas M. Hohlbaum, Signa Moe, Ann Marshak-Rothstein
Journal: The Journal of Experimental Medicine (2000)

Fas ligand (FasL) has been shown to mediate both apoptotic and inflammatory reactions. To rigorously assess the physiological role of different forms of the FasL molecule with regard to these two distinct processes, we isolated stably transfected lymphoma cell lines that expressed either murine wild-type FasL, membrane-only FasL, or functionally distinct forms of soluble FasL. First, the ability of these lines to induce an inflammatory response was assessed in vivo by injecting the transfectants intraperitoneally and measuring subsequent neutrophil extravasation into the peritoneal cavity. Second, lines were assessed by injecting the transfectants subcutaneously and monitoring their growth as solid tumors. Our study clearly demonstrated that the extent of inflammation induced by the transfectants directly correlated with their relative cytotoxic activities. A neutrophil response could only be elicited in mice with intact Fas death domains although Fas expression by the neutrophils was not essential. Lymphoma cells expressing the soluble FasL form corresponding to the natural cleavage product could not trigger apoptosis and did not induce a neutrophil response. In contrast to the other FasL transfectants, these cells survived as tumor transplants. However, expression of soluble FasL was not benign, but actually suppressed the inflammatory response and protected other transfectants from the effector mechanisms elicted by membrane-bound FasL.
Gα <sub>i2</sub> but Not Gα <sub>i3</sub> Is Required for Muscarinic Inhibition of Contractility and Calcium Currents in Adult Cardiomyocytes
Authors: Kohzo Nagata, Chianping Ye, Mohit Jain, David S. Milstone, Ronglih Liao, Richard M. Mortensen
Journal: Circulation Research (2000)

Abstract —Parasympathetic stimulation of the heart acts through M 2 -muscarinic acetylcholine receptors to regulate ion channel activity and subsequent inotropic status. Although muscarinic signal transduction is mediated via pertussis toxin-sensitive G proteins Gα i/o , the specific signal transduction requirements of Gα i2 and Gα i3 in mediating muscarinic regulated L-type calcium currents ( I Ca, L ), intracellular calcium, and cell contractility remain to be determined. Adult ventricular myocytes were isolated from Gα i2 -null mice, Gα i3 -null mice, and their wild-type littermates. Cell shortening, intracellular calcium levels, and I Ca, L were all measured in response to isoproterenol, a β-adrenergic receptor agonist, and carbachol, a cholinergic receptor agonist. With isoproterenol stimulation, myocytes from all groups demonstrated a marked increase in calcium currents, correlating with augmented intracellular calcium transient amplitude and cell shortening. Carbachol significantly attenuated the isoproterenol response in wild-type and Gα i3 -null cells but had no effect in Gα i2 -null cells. This study demonstrates that Gα i2 , but not Gα i3 , is required for muscarinic inhibition of the β-adrenergic response in adult murine ventricular myocytes.
Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia
Authors: F. Scaglione, S. Esposito, S. Leone, V. Lucini, M. Pannacci, L. Ma, G. L. Drusano
Journal: European Respiratory Journal (2009)

Nosocomial pneumonia (NP) is associated with considerable morbidity and mortality. Data have shown that inadequate initial antibiotic therapy is a major risk for infection-attributed mortality. The aim of the present study was to measure antibiotic concentration and minimum inhibitory concentration (MIC) in infected hospitalised patients early in therapy, in order to determine whether dose alterations, in those with low drug concentrations, could affect outcomes. Only patients treated with aminoglycosides, fluoroquinolones, and β-lactams were evaluated. MICs were determined using standard National Committee for Clinical Laboratory Standards procedures. Antibiotics were assayed using validated high-performance liquid chromatographic methods. Pharmacokinetic/pharmacodynamic markers adopted were: aminoglycoside peak/MIC ratio ≥8 mg·L −1 ; fluoroquinolone peak/MIC ≥10 mg·L −1 ; β-lactam peak/MIC ≥4 mg·L −1 and time that plasma levels remain above the MIC ≥70%. 638 patients with NP were included in the study. In 205 patients, both drug concentration and isolate MIC were available, while in other patients, used as controls, one or both parameters were lacking. For clinical outcome, the Acute Physiology and Chronic Health Evaluation II score (p&lt;0.0001), the presence of combination therapy (p = 0.0014) and whether both MIC and drug concentration(s) were measured (p = 0.0002) significantly affected the probability of a good outcome. For microbiological outcome, the MIC for the β-lactams (≤2 mg·L −1 ; p&lt;0.0001) and whether the second drug was a fluoroquinolone or aminoglycoside (fluoroquinolones were better than aminoglycosides; p = 0.0177), as well as whether both MIC and drug concentration(s) were measured (p = 0.02), affected the probability of eradication. Measurement of drug concentrations and determination of pathogen MIC values with subsequent dose alteration significantly improves the probability of good clinical outcome and pathogen eradication in NP.
Menin Inactivation Leads to Loss of Transforming Growth Factor β Inhibition of Parathyroid Cell Proliferation and Parathyroid Hormone Secretion
Authors: Hideaki Sowa, Hiroshi Kaji, Riko Kitazawa, Sohei Kitazawa, Tatsuo Tsukamoto, Shozo Yano, Toshihiko Tsukada, Lucie Canaff, Geoffrey N. Hendy, Toshitsugu Sugimoto, Kazuo Chihara
Journal: Cancer Research (2004)

Abstract Primary hyperparathyroidism is a common endocrine disorder caused by parathyroid gland enlargement and excessive parathyroid hormone (PTH) secretion. However, the precise mechanisms of tumorigenesis of the parathyroids are unknown. Here we have investigated the roles of transforming growth factor (TGF)-β and menin, the product of the multiple endocrine neoplasia type 1 (Men1) gene, in the proliferation and PTH production of parathyroid cells from either patients with secondary hyperparathyroidism or Men1. TGF-β was expressed in the parathyroid endocrine cells. Addition of TGF-β to parathyroid cells from patients with secondary hyperparathyroidism inhibited their proliferation and PTH secretion. These responses to TGF-β were lost when menin was specifically inactivated by antisense oligonucleotides. Moreover, TGF-β did not affect the proliferation and PTH production of parathyroid cells from a Men1 patient. These results indicate that menin is required for TGF-β action in the parathyroid. We conclude that TGF-β is an important autocrine/paracrine negative regulator of parathyroid cell proliferation and PTH secretion and that loss of TGF-β signaling due to menin inactivation contributes to parathyroid tumorigenesis.
Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non–Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial
Authors: Ulrich Gatzemeier, Anna Pluzanska, Aleksandra Szczesna, Eckhard Kaukel, Jaromir Roubec, Flavio De Rosa, Janusz Milanowski, Hanna Karnicka-Mlodkowski, Milos Pesek, Piotr Serwatowski, Rodryg Ramlau, Terezie Janaskova, Johan Vansteenkiste, Janos Strausz, Georgy Moiseevich Manikhas, Joachim Von Pawel
Journal: Journal of Clinical Oncology (2007)

Erlotinib is a potent inhibitor of the epidermal growth factor receptor tyrosine kinase, with single-agent antitumor activity. Preclinically, erlotinib enhanced the cytotoxicity of chemotherapy. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of erlotinib in combination with cisplatin and gemcitabine as first-line treatment for advanced non-small-cell lung cancer (NSCLC).Patients received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1). The primary end point was overall survival (OS). Secondary end points included time to disease progression (TTP), response rate (RR), duration of response, and quality of life (QoL).A total of 1,172 patients were enrolled. Baseline demographic and disease characteristics were well balanced. There were no differences in OS (hazard ratio, 1.06; median, 43 v 44.1 weeks for erlotinib and placebo groups, respectively), TTP, RR, or QoL between treatment arms. In a small group of patients who had never smoked, OS and progression-free survival were increased in the erlotinib group; no other subgroups were found more likely to benefit. Erlotinib with chemotherapy was generally well tolerated; incidence of adverse events was similar between arms, except for an increase in rash and diarrhea with erlotinib (generally mild).Erlotinib with concurrent cisplatin and gemcitabine showed no survival benefit compared with chemotherapy alone in patients with chemotherapy-naïve advanced NSCLC.
Effects of Adenosinetriphosphate and Potassium Chloride on Ventricular Fibrillation Induced by Lack of Substrates
Authors: Mario Penna, Alejandro Illanes, Marcos Pupkin
Journal: Circulation Research (1962)

The perfusion of the isolated guinea pig or cat heart with a substrate-free Tyrode solution induces a decrease in rate, a lengthening of the P-R interval, a decreased amplitude of the R wave, ventricular premature contractions, A-V dissociation, insignificant changes of the Q-T interval, and, finally, ventricular fibrillation with a regular atrial rhythm. In isolated hearts of both species, the reversal of ventricular fibrillation induced by lack of metabolites was attempted as follows: in guinea pig hearts, increasing the potassium chloride concentration of the Tyrode solution without glucose to 5.4 mM/L. reversed ventricular fibrillation in all cases. Adenosinetriphosphate (ATP) reversed this arrhythmia in only two of seven cases. However, in the isolated cat heart, potassium chloride in the same concentration (5.4 mM/L.) reversed ventricular fibrillation only in three out of seven cases. ATP did not reverse ventricular fibrillation in any cases, but potassium given with ATP reversed this arrhythmia in two out of four cases. In the cat heart, the reversal of ventricular fibrillation in all cases was accomplished only by increasing potassium chloride concentration to 5.4 mM/L. and adding glucose (1 Gm./L.).
Redundancy in the nervous system: Where internal models collapse
Authors: Ramesh Balasubramaniam
Journal: Behavioral and Brain Sciences (2004)

Grush has proposed a fairly comprehensive version of the idea of internal models within the framework of the emulation theory of representation. However, the formulation suffers from assumptions that render such models biologically infeasible. Here I present some problems from physiological principles of human movement production to illustrate why. Some alternative views to emulation are presented.
Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: a report from the National Wilms' Tumor Study Group.
Authors: D M Green, N E Breslow, J B Beckwith, J Z Finklestein, P E Grundy, P R Thomas, T Kim, S J Shochat, G M Haase, M L Ritchey, P P Kelalis, G J D'Angio
Journal: Journal of Clinical Oncology (1998)

PURPOSE The National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS Between August 6, 1986 and September 1, 1994, 1,687 previously untreated children less than 16 years of age with stages I to II/favorable histology (FH) or stage I/anaplastic histology WT (low-risk [LR] group) or stages III to IV/FH WT or stages I to IV/clear cell sarcoma of the kidney (high-risk [HR] group) were randomized to treatment that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either STD courses (3 days) or PI treatment with doxorubicin. RESULTS The 2-year relapse-free survival (RFS) rates for LR patients were 91.3% for 544 randomized to treatment with PI and 91.4% for 556 randomized to treatment with STD chemotherapy (P = .988). The 2-year RFS rates for HR patients were 87.3% for 299 randomized to treatment with PI and 90.0% for 288 randomized to treatment with STD chemotherapy (P = .865). CONCLUSION We conclude that patients treated with PI combination chemotherapy for LR or HR WT or clear cell sarcoma of the kidney have equivalent 2-year RFS to those treated with STD regimens. PI drug administration is recommended as the new standard based on demonstrated efficacy, greater administered dose-intensity, less severe hematologic toxicity, and the requirement for fewer physician and hospital encounters.