tbuckley/cabot-search huggingface dataset:
Increased Circulating Endothelial Progenitor Cells Are Associated with Survival in Acute Lung Injury
Authors: Ellen L. Burnham, W. Robert Taylor, Arshed A. Quyyumi, Mauricio Rojas, Kenneth L. Brigham, Marc Moss
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Repair of damaged endothelium is important in recovery from acute lung injury. In animal models, bone marrow–derived endothelial progenitor cells differentiate into mature endothelium and assist in repairing damaged vasculature.Objectives: The quantity of endothelial progenitor cells in patients with acute lung injury is unknown. We hypothesize that increased numbers of circulating endothelial progenitor cells will be associated with an improved outcome in acute lung injury and the acute respiratory distress syndrome.Methods: Peripheral blood mononuclear cells from the buffy coat of patients with early acute lung injury (n = 45), intubated control subjects (n = 10), and healthy volunteers (n = 7) were isolated using Ficoll density gradient centrifugation, and plated on fibronectin-coated cellware. After 24 hours, nonadherent cells were removed and replated on fibronectin-coated cellware at a concentration of 1 × 106 cells/well. Colony-forming units were counted after 7 days' incubation.Measurements/Main Results: Endothelial progenitor cell colony numbers were significantly higher in patients with acute lung injury compared with healthy control subjects (p < 0.05), but did not differ between patients with acute lung injury and intubated control subjects. However, in the 45 patients with acute lung injury, improved survival correlated with a higher colony count (p < 0.04). Patients with acute lung injury with a colony count of ⩾ 35 had a mortality of 30%, compared with 61% in those with colony counts < 35 (p < 0.03), results that persisted in a multivariable analysis correcting for age, sex, and severity of illness.Conclusions: An increased number of circulating endothelial progenitor cells in acute lung injury is associated with improved survival.
Second Malignant Neoplasms and Cardiovascular Disease Following Radiotherapy
Authors: Lois B. Travis, Andrea K. Ng, James M. Allan, Ching-Hon Pui, Ann R. Kennedy, X. George Xu, James A. Purdy, Kimberly Applegate, Joachim Yahalom, Louis S. Constine, Ethel S. Gilbert, John D. Boice
Journal: JNCI Journal of the National Cancer Institute (2012)

Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies.
Basal or stress-induced cortisol and asthma development: the TRAILS study
Authors: Nienke M. Vink, H. Marike Boezen, Dirkje S. Postma, Judith G.M. Rosmalen
Journal: European Respiratory Journal (2012)

We examined the association between: 1) cortisol levels and asthma or asthma development; 2) cortisol levels upon stress and asthma. In addition, we performed a <i>post hoc</i> meta-analysis on results from the literature. Cortisol, cortisol upon stress, asthma (doctor diagnosis of asthma and/or symptoms and/or treatment in the past 12 months) and asthma development (asthma at a specific survey while not having asthma at the previous survey(s)) were assessed in the TRAILS study (n=2230, mean age at survey 1 11 years, survey 2 14 years and survey 3 16 years). Logistic regression models were used to study associations between: 1) cortisol (cortisol awakening response, area under the curve (AUC) with respect to the ground (AUCg) or with respect to the increase (AUCi), and evening cortisol) and asthma or asthma development; 2) cortisol upon stress (AUCg or AUCi) and asthma. The meta-analyses included nine case–control articles on basal cortisol in asthma. No significant association was found between: 1) cortisol and asthma (age 11 years) or asthma development (age 14 or 16 years); 2) cortisol upon stress and asthma (age 16 years). The meta-analysis found lower morning and evening cortisol levels in asthmatics compared to non-asthmatics; however, the summary estimates were not significant. We found no evidence supporting a role for cortisol in asthma and asthma development.
Continuing rearrangement but absence of somatic hypermutation in immunoglobulin genes of human B cell precursor leukemia.
Authors: J Bird, N Galili, M Link, D Stites, J Sklar
Journal: The Journal of Experimental Medicine (1988)

Southern blot analyses revealed that cells from nearly 30% of childhood B cell precursor acute lymphoblastic leukemias (ALLs) contained more than two rearranged, nongermline bands for Ig heavy chain genes. DNA corresponding to these bands was molecularly cloned from two cases which showed three and seven rearranged bands, respectively. Nucleotide sequence analysis of the cloned DNA demonstrated that each band represented different VDJ or DJ rearrangements. While the same DJ joints were shared by several rearrangements, different DJ joints were found in the majority of rearrangements, precluding V region substitution as an explanation for the multiplicity of heavy chain rearrangements in these leukemias. Most of the V region segments involved in these rearrangements were restricted to VH region families that have been shown previously to be preferentially rearranged in human fetal B lineage cells. Sequence analysis of multiple copies of the same VDJ rearrangements from different cells revealed no somatic mutation, a mechanism responsible for detection of extra rearranged Ig DNA bands in certain other B lineage tumors. The data suggest that in some cases of ALL Ig heavy chain genes begin and continue to rearrange de novo within the neoplastic B cell precursor populations derived from an original malignant cell transformed at a stem cell stage of differentiation.
Independent origin of mono-rifampin-resistant Mycobacterium tuberculosis in patients with AIDS.
Authors: M Lutfey, P Della-Latta, V Kapur, L A Palumbo, D Gurner, G Stotzky, K Brudney, J Dobkin, A Moss, J M Musser, B N Kreiswirth
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Historically, infections caused by Mycobacterium tuberculosis have been treated simultaneously with isoniazid and rifampin. As a consequence of this combined therapy, strains resistant only to rifampin were rarely recovered. However, recently there has been an increasing number of reports describing HIV-positive patients infected with mono-rifampin-resistant M. tuberculosis strains. Organisms cultured from seven patients (including six with AIDS) with infections caused by mono-rifampin-resistant M. tuberculosis, and seen at one New York City hospital, were analyzed by molecular techniques to test the hypothesis that dissemination of a single clone had occurred. IS6110 DNA fingerprinting and automated DNA sequencing of a region of the RNA polymerase beta subunit structural gene (rpoB) containing mutations that confer rifampin resistance showed that all organisms independently acquired the mono-rifampin-resistant phenotype. Molecular analysis of mono-rifampin-resistant organisms cultured from 13 additional patients in New York City confirmed independent strain origin. The data rule out the possibility of person-to-person strain transmission among these patients, and they suggest that host factors such as poor compliance with antituberculosis medications or decreased absorption of rifampin have been a driving force in the origin of these strains.
A Randomized Phase II Pharmacokinetic and Pharmacodynamic Study of Indisulam as Second-Line Therapy in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Denis C. Talbot, Joachim von Pawel, Emma Cattell, S. Murray Yule, Claire Johnston, Anthe S. Zandvliet, Alwin D.R. Huitema, Chris J. Norbury, Paul Ellis, Leon Bosquee, Martin Reck
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The primary aim of this study was to measure the objective tumor response rate following treatment with indisulam [E7070; N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide] as second-line therapy in patients with advanced non–small cell lung cancer. The secondary aims were to determine progression-free survival, to assess the safety and tolerability of indisulam, and to study its pharmacokinetic and pharmacodynamic profile. Experimental Design: Patients were randomized to receive indisulam every 3 weeks either as a single i.v. dose of 700 mg/m2 on day one (dx1) or 130 mg/m2 given on days 1 to 5 inclusive as a daily infusion (dx5). All patients had previously received platinum-based chemotherapy. Results: Forty-four patients were randomized. Only minor responses were seen. Myelosuppression, gastrointestinal symptoms, and lethargy were the most common toxicities and were more frequent in the dx1 arm. The pharmacokinetics of indisulam in each treatment schedule were adequately described using a previously developed population pharmacokinetic model and were mostly consistent with the results of the phase I program. Flow cytometric analysis of endobronchial and metastatic disease revealed a reduction in the fraction of cycling cells and an increase in apoptosis following indisulam compared with pretreatment levels. Conclusions: We conclude that, despite evidence of tumor-specific indisulam-induced apoptosis, neither of these treatment schedules has single-agent activity as second-line treatment of non–small cell lung cancer.
Essential role of Rho/ROCK-dependent processes and actin dynamics in mediating leptin-induced hypertrophy in rat neonatal ventricular myocytes
Authors: A ZEIDAN, S JAVADOV, M KARMAZYN
Journal: Cardiovascular Research (2006)

Obesity is associated with increased leptin production, which may contribute to cardiac hypertrophy. Although leptin has been shown to produce cardiomyocyte hypertrophy, its mechanism of action is far from clear. Rho proteins have been suggested as major contributors to cardiac hypertrophy, although their potential role in mediating the effect of leptin has not been studied.We determined the role of Rho and Rho-associated kinase (ROCK) as mediators of leptin-induced cell hypertrophy in cultured neonatal rat ventricular myocytes.Leptin (3.1 nmol/L) significantly increased cell surface area by 32+/-5% and leucine incorporation by 43 +/- 7%. These effects were associated with significant activation of RhoA to 450 +/- 40% of pre-leptin levels that was attenuated by pretreatment with an anti-leptin receptor (anti-OBR) antibody (166 ng/mL) to 120 +/- 20% of control values. Both the RhoA inhibitor C3 exoenzyme and ROCK inhibitor Y-27632 potently attenuated leptin-induced increased cell surface area and leucine incorporation. The hypertrophic effect of leptin was associated with an increase in phosphorylation of the actin binding protein cofilin to 290 +/- 20% of control values. In addition, the increase in polymerization of actin, as reflected by a decrease in the G/F-actin ratio, was significantly inhibited by both the anti-OBR antibody and Y-27632. Leptin-induced hypertrophy was also attenuated by disruption of actin filaments with 50 nmol/L latrunculin B. RhoA pathway inhibitors and latrunculin B also both attenuated leptin-induced ERK1/2 and p38 activation.Our results indicate that the activation of Rho and actin dynamics play a pivotal role in leptin signaling leading to the development of cardiomyocyte hypertrophy.
Remnant kidney metabolism in the dog.
Authors: A Fine
Journal: Journal of the American Society of Nephrology (1991)

A marked increase in oxygen uptake (Qo2) per nephron has been described in the remnant kidney of the rat. However, it is not known which substrates support renal metabolism in remnant kidney nor is it known whether similar changes in Qo2 occur in other species. Remnant kidney in the dog was induced by ligation of 60 to 75% of the renal arterial branches on one side followed 1 to 2 wk later by contralateral nephrectomy. At 3 months marked hypertrophy of the remnant kidney was found and the glomerular filtration rate was 18 +/- 1.8 mL/min compared with 31 +/- 2 in a normal kidney (P less than 0.01). Qo2 was 689 +/- 60 mumol/min/100 mL glomerular filtration rate in the remnant kidney compared with 564 +/- 42 mumol/min/100 mL glomerular filtration rate in the normal kidney (P less than 0.01). Total renal ammoniagenesis per nephron increased to values found in chronic metabolic acidosis although serum (K+) and (HCO3-) were no different than in the normal dog. The oxidation of glutamine and lactate by remnant kidneys accounted for over 80% of Qo2, similar to that of normal kidneys. It is concluded that hypermetabolism per nephron occurs in the remnant kidney of the dog and that glutamine and lactate are the major energy substrates in remnant kidney. Furthermore, factors other than serum (K+) and (HCO3-) augment ammoniagenesis in this model. However, when these results are expressed per whole kidney or per gram of tissue, hypermetabolism does not occur in these remnant kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrophysiological effects of hypertonic sucrose solutions on canine cardiac Purkinje fibers.
Authors: J C Bailey
Journal: Circulation Research (1981)

Microelectrode techniques were used to study the electrophysiological effects of hypertonic solutions on canine cardiac Purkinje fibers. Tyrode's solution was rendered hyperosmotic by the addition of sucrose to produce 320, 350, 400, and 500 mOsm solutions. Hyperosmotic solutions produced sucrose concentration-dependent hyperpolarization, increased the current required to effect all-or-none depolarization, slowed transmission, and prolonged action potential duration. The action potential prolongation was reversed or prevented by lidocaine (10-5 M). Treatment of potassium-depolarized Purkinje fibers with hypertonic solutions produced hyperpolarization, increased Vmax phase 0, decreased the current required to evoke all-or-none depolarization, increased action potential duration, and increased transmission speed. The potent electrophysiological actions of hypertonic sucrose solutions probably derive from their osmotic effects rather than from selective actions at specific membrane sites or hormone receptors.
Prehypertension Increases the Risk for Renal Arteriosclerosis in Autopsies
Authors: Toshiharu Ninomiya, Michiaki Kubo, Yasufumi Doi, Koji Yonemoto, Yumihiro Tanizaki, Kazuhiko Tsuruya, Katsuo Sueishi, Masazumi Tsuneyoshi, Mitsuo Iida, Yutaka Kiyohara
Journal: Journal of the American Society of Nephrology (2007)

Information regarding the association between prehypertension BP level and renal arteriosclerosis is limited. In 652 consecutive population-based autopsy samples without hypertension treatment before death, the relationship between the severity of renal arteriosclerosis and BP levels classified according to the criteria of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure was examined. The age- and gender-adjusted frequencies of renal arteriosclerosis linearly increased with elevating BP levels; both hypertensive and prehypertensive subjects had significantly higher frequencies of renal arteriosclerosis than subjects with normal BP (normal 11.9%; prehypertension 28.5%; stage 1 hypertension 32.9%; stage 2 hypertension 58.2%; all P < 0.01 versus normal). In a logistic regression model, prehypertension was significantly associated with renal arteriosclerosis after adjustment for other cardiovascular risk factors (prehypertension multivariate-adjusted odds ratio [mOR] 5.99 [95% confidence interval (CI) 2.20 to 15.97]; stage 1 hypertension mOR 6.99 [95% CI 2.61 to 18.72]; stage 2 hypertension mOR 22.21 [95% CI 8.35 to 59.08]). This significant association was observed for all renal arterial sizes. The similar association was also observed for arteriolar hyalinosis. When the subjects were divided into those with and those without target organ damage, the impact of prehypertension on renal arteriosclerosis was similar for both groups (subjects without target organ damage mOR 5.04 [95% CI 1.36 to 18.62]; subjects with target organ damage mOR 6.42 [95% CI 1.29 to 32.04]). These findings suggest that both hypertension and prehypertension are associated significantly with the severity of renal arteriosclerosis, regardless of the presence or absence of target organ damage.
The OGF-OGFr axis utilizes the p21 pathway to restrict progression of human pancreatic cancer
Authors: Fan Cheng, Patricia J McLaughlin, Michael F Verderame, Ian S Zagon
Journal: Molecular Cancer (2008)

Abstract Background Pancreatic cancer is the 4th leading cause of death from cancer in the U.S. The opioid growth factor (OGF; [Met 5 ]-enkephalin) and the OGF receptor form an inhibitory growth regulatory system involved in the pathogenesis and treatment of pancreatic cancer. The OGF-OGFr axis influences the G 0 /G 1 phase of the cell cycle. In this investigation, we elucidate the pathway of OGF in the cell cycle. Results Using BxPC-3 cells, OGF decreased phosphorylation of retinoblastoma (Rb) protein without changing total Rb. This change was correlated with reduced cyclin-dependent kinase protein (Cdk) 2 kinase activity, but not total Cdk2. OGF treatment increased cyclin-dependent kinase inhibitor (CKI) p21 protein expression in comparison to controls, as well levels of p21 complexed with Cdk2. Naloxone abolished the increased expression of p21 protein by OGF, suggesting a receptor-mediated activity. p21 specific siRNAs blocked OGF's repressive action on proliferation in BxPC-3, PANC-1, and Capan-2 cells; cells transfected with negative control siRNA had no alteration in p21 expression, and therefore were inhibited by OGF. Conclusion These data are the first to reveal that the target of cell proliferative inhibitory action of OGF in human pancreatic cancer is a p21 CKI pathway, expanding strategies for diagnosis and treatment of these neoplasias.
Childhood Videotaped Social and Neuromotor Precursors of Schizophrenia: A Prospective Investigation
Authors: Jason Schiffman, Elaine Walker, Morten Ekstrom, Fini Schulsinger, Holger Sorensen, Sarnoff Mednick
Journal: American Journal of Psychiatry (2004)

The authors examined videotaped behaviors of children who developed schizophrenia as adults and of comparison subjects to disclose possible social and neuromotor deficits foreshadowing later development of schizophrenia.In 1972, a sample of 265 11-13-year-old Danish children were filmed under standardized conditions while they were eating lunch. The examination was part of a larger study investigating early signs of schizophrenia spectrum disorders. Many of the subjects had a parent with schizophrenia, leaving them at high risk for developing a schizophrenia spectrum disorder. In 1991, adult psychiatric outcome data were obtained for 91.3% (N=242). This study systematically analyzed the videotapes to determine whether the children who developed schizophrenia as adults evidenced greater social and/or neuromotor deficits than children who did not develop a psychiatric disorder and children who developed other psychiatric disorders.The findings from this study suggest that the brief videotaped footage of children eating lunch was able to discriminate between the individuals who later developed schizophrenia and those who did not. Specifically, the preschizophrenia children evidenced differences on measures of sociability and general neuromotor functioning (among boys) from the children who developed other psychiatric disorders and the children who did not develop a psychiatric disorder.Social and neuromotor deficits specific to children who develop schizophrenia in adulthood provide further support for a neurodevelopmental hypothesis of schizophrenia.
Current Progress in Reactive Oxygen Species (ROS)‐Responsive Materials for Biomedical Applications
Authors: Sue Hyun Lee, Mukesh K. Gupta, Jae Beum Bang, Hojae Bae, Hak‐Joon Sung
Journal: Advanced Healthcare Materials (2013)

Recently, significant progress has been made in developing “stimuli-sensitive” biomaterials as a new therapeutic approach to interact with dynamic physiological conditions. Reactive oxygen species (ROS) production has been implicated in important pathophysiological events, such as atherosclerosis, aging, and cancer. ROS are often overproduced locally in diseased cells and tissues, and they individually and synchronously contribute to many of the abnormalities associated with local pathogenesis. Therefore, the advantages of developing ROS-responsive materials extend beyond site-specific targeting of therapeutic delivery, and potentially include navigating, sensing, and repairing the cellular damages via programmed changes in material properties. Here we review the mechanism and development of biomaterials with ROS-induced solubility switch or degradation, as well as their performance and potential for future biomedical applications.