tbuckley/cabot-search huggingface dataset:
miR-141 Is a Key Regulator of Renal Cell Carcinoma Proliferation and Metastasis by Controlling EphA2 Expression
Authors: Xuanyu Chen, Xuegang Wang, Anming Ruan, Weiwei Han, Yan Zhao, Xing Lu, Pei Xiao, Hangchuan Shi, Rong Wang, Li Chen, Shaoyong Chen, Quansheng Du, Hongmei Yang, Xiaoping Zhang
Journal: Clinical Cancer Research (2014)

Although microRNAs (miRNA) have been revealed as crucial modulators of tumorigenesis, our understanding of their roles in renal cell carcinoma (RCC) is limited. Here we sought to identify human miRNAs that act as key regulators of renal carcinogenesis.We performed microarray-based miRNA profiling of clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-141 both in vitro and in vivo, which was the most significantly downregulated in ccRCC tissues.A total of 74 miRNAs were dysregulated in ccRCC compared with normal tissues. miR-141 was remarkably downregulated in 92.6% (63/68) ccRCC tissues and would serve as a promising biomarker for discriminating ccRCC from normal tissues with an area under the receiver operating characteristics curve of 0.93. Overexpression of miR-141 robustly impaired ccRCC cell migratory and invasive properties and suppressed cell proliferation by arresting cells at G0-G1 phase in vitro and in human RCC orthotopic xenografts. Significantly, the antitumor activities of miR-141 were mediated by its reversal regulation of erythropoietin-producing hepatocellular (Eph) A2 (EphA2), which then relayed a signaling transduction cascade to attenuate the functions of focal adhesion kinase (FAK), AKT, and MMP2/9. In addition, a specific and inverse correlation between miR-141 and EphA2 expression was obtained in human ccRCC samples. Finally, miR-141 could be secreted from the ccRCC donor cells, and be taken up and function moderately in the ccRCC recipient cells.miR-141 serves as a potential biomarker for discriminating ccRCC from normal tissues and a crucial suppressor of ccRCC cell proliferation and metastasis by modulating the EphA2/p-FAK/p-AKT/MMPs signaling cascade.
Alternative pathway of complement: recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of the pathway.
Authors: R G Medicus, O Götze, H J Müller-Eberhard
Journal: The Journal of Experimental Medicine (1976)

In this study the physiological role of properdin and the differential subunit composition of the solid phase enzymes of the pathway have been explored. Cell-bound C3 and C5 convertase differ in their C3b requirement. Apparently one molecule of C3b is sufficient to allow formation of C3 convertase (C3b,B), whereas two or more are required for generation of C5 convertase (C3bn,B). This conclusion was drawn from results indicating the critical role of the spacial distribution of C3b molecules on the cell surface in enzyme formation. While the C3/C5 convertase is fully capable of acting on C5 and thereby initiating the assembly of the cytolytic membrane attack complex, it is exceedingly labile and vulnerable to destruction by the C3b inactivator. It is the apparent role of properdin to confer a degree of stability upon the labile enzyme and to protect its C3 convertase function against enzymatic destruction. To achieve these effects, precursor properdin (pre-P) is recruited in a binding-activation reaction by the labile C3/C5 convertase. Multiple C3b molecules appear to be needed for the formation of properdin-activating principle. Three modes of regulation have been described, which involve spontaneous dissociation enzymatic degradation by C3b inactivator and disassembly by beta1H. The functional differences of pre-P and activated properdin (P) were delineated, pre-P displaying a weak affinity for C3b and P the capacity of strong interaction, P generating a soluble C3 convertase in serum and pre-P being unable to do so. Because of the profound differences between native pre-P and the laboratory product P, the question was raised as to whether soluble P represents an unphysiological form of the protein. On the basis of this and other studies, the conclusion was reached that in vitro properdin recruitment constitutes the terminal event of the properdin pathway, and that properdin augments the function of C3/C5 convertase without changing its substrate specificity.
The effect of airway pressure and oscillation amplitude on ventilation in pre-term infants
Authors: Martijn Miedema, Frans H. de Jongh, Inez Frerichs, Mariette B. van Veenendaal, Anton H. van Kaam
Journal: European Respiratory Journal (2012)

We determined the effect of lung recruitment and oscillation amplitude on regional oscillation volume and functional residual capacity (FRC) in high-frequency oscillatory ventilation (HFOV) used in pre-term infants with respiratory distress syndrome (RDS). Changes in lung volume, oscillation volume and carbon dioxide levels were recorded in 10 infants during a stepwise recruitment procedure, and an increase in pressure amplitude of 5 cmH(2)O was measured using electrical impedance tomography and transcutaneous monitoring. The pressures at maximal respiratory system compliance, maximal oscillation volume and minimal carbon dioxide levels were determined. Impedance data were analysed for the chest cross-section and predefined regions of interest. Despite the fixed pressure amplitude, the oscillation volume changed during the incremental pressure steps following a parabolic pattern, with an inverse relationship to the carbon dioxide pressures. The pressures corresponding with maximal compliance, maximal oscillation volume and minimal carbon dioxide were similar and highly correlated. Regional analysis showed similar findings. The increase in pressure amplitude resulted in increased oscillation volumes and decreased carbon dioxide levels, while FRC remained unchanged. In HFV pre-term infants with RDS, oscillation volumes are closely related to the position of ventilation in the pressure-volume envelope and the applied pressure amplitude. Changes in pressure amplitude do not seem to affect FRC.
Paget disease of bone
Authors: G. David Roodman, Jolene J. Windle
Journal: Journal of Clinical Investigation (2005)

Paget disease of bone (PD) is characterized by excessive bone resorption in focal areas followed by abundant new bone formation, with eventual replacement of the normal bone marrow by vascular and fibrous tissue. The etiology of PD is not well understood, but one PD-linked gene and several other susceptibility loci have been identified, and paramyxoviral gene products have been detected in pagetic osteoclasts. In this review, the pathophysiology of PD and evidence for both a genetic and a viral etiology for PD will be discussed.
Role of metabolic CO2 production in ventilatory response to steady-state exercise.
Authors: E A Phillipson, G Bowes, E R Townsend, J Duffin, J D Cooper
Journal: Journal of Clinical Investigation (1981)

We examined the role of metabolic CO2 production in the hyperpnea of muscular exercise by comparing the response of alveolar ventilation to moderate levels of exercise with the response to venous infusion of CO2 at rest. Studies were performed in four awake sheep that were trained to run on a treadmill. The sheep had been cannulated for veno-venous extracorporeal perfusion so that CO2 could be infused into the peripheral venous blood through membrane lungs in the perfusion circuit. The sheep breathed room air through an endo-tracheal tube inserted through a tracheostomy, and samples of expired gas were collected for measurement of the rates of CO2 production and O2 consumption. All measurements were made in the steady state. In each of the four sheep, the relationship between alveolar ventilation and the rate of CO2 production could be described by a single linear function (r greater than 0.99; P less than 0.001), regardless of whether CO2 production was increased by exercise, venous CO2 infusion, or combinations of both procedures. This relationship applied for values of CO2 production up to 350% of control. In contrast, no unique relationship was found between the rate of alveolar ventilation and either the rate of O2 consumption, cardiac output, or mixed venous blood gas pressures. The findings indicate that the hyperpnea of mild to moderate steady-state exercise can be attributed to the associated increase in the rate of CO2 production. Therefore, there is no need to invoke obligatory nonmetabolic stimuli to account for the ventilatory response to steady-state exercise.
The Concise Handbook of Family Cancer Syndromes
Authors: Noralane M. Lindor, Mark H. Greene
Journal: JNCI Journal of the National Cancer Institute (1998)

11. Cowden syndrome (gingival multiple hamartoma syndrome) 1051 12. Esophageal cancer, tylosis with (nonepidermolytic palmoplantar keratosis and Howel-Evans’ syndrome) 1052 13. Fanconi’s anemia (includes pancytopenia, Fanconi’s type) 1053 14. Gastric cancer, familial 1054 15. Hodgkin’s disease, familial 1054 16. Li-Fraumeni syndrome 1055 17. Melanoma, familial with or without dysplastic nevi (includes dysplastic nevus syndrome, familial atypical mole–malignant melanoma syndrome, and melanoma–astrocytoma syndrome) 1056
Lack of association of group specific component haplotypes with lung function in smokers
Authors: I Kasuga
Journal: Thorax (2003)

Airway inflammation may affect the decrease in lung function that occurs in response to cigarette smoke, and is an important pathological feature in chronic obstructive pulmonary disease (COPD). Group specific component (GC) can act as an inflammatory mediator and may therefore have important influences on the inflammatory reaction in the airway. Several reports have described associations between GC haplotypes and COPD but these remain controversial. In addition, most of these studies were based on a small number of subjects.We have studied the contribution of GC haplotypes to the level of lung function in a large cohort of smokers with high or low lung function (mean FEV(1) % predicted 91.8 and 62.6, respectively). The frequency of the three major GC haplotypes (1S, 1F and 2) was investigated in 537 individuals with high lung function and 533 with low lung function.No significant difference was found in the frequency of any GC haplotype between the high and low lung function groups. There was also no significant difference between the groups in genotype frequency of the two single nucleotide polymorphisms that underlie the haplotypes.The GC haplotype does not contribute to reduced lung function in this cohort of smokers.
Why Is Spiritual Care Infrequent at the End of Life? Spiritual Care Perceptions Among Patients, Nurses, and Physicians and the Role of Training
Authors: Michael J. Balboni, Adam Sullivan, Adaugo Amobi, Andrea C. Phelps, Daniel P. Gorman, Angelika Zollfrank, John R. Peteet, Holly G. Prigerson, Tyler J. VanderWeele, Tracy A. Balboni
Journal: Journal of Clinical Oncology (2012)

To determine factors contributing to the infrequent provision of spiritual care (SC) by nurses and physicians caring for patients at the end of life (EOL).This is a survey-based, multisite study conducted from March 2006 through January 2009. All eligible patients with advanced cancer receiving palliative radiation therapy and oncology physician and nurses at four Boston academic centers were approached for study participation; 75 patients (response rate = 73%) and 339 nurses and physicians (response rate = 63%) participated. The survey assessed practical and operational dimensions of SC, including eight SC examples. Outcomes assessed five factors hypothesized to contribute to SC infrequency.Most patients with advanced cancer had never received any form of spiritual care from their oncology nurses or physicians (87% and 94%, respectively; P for difference = .043). Majorities of patients indicated that SC is an important component of cancer care from nurses and physicians (86% and 87%, respectively; P = .1). Most nurses and physicians thought that SC should at least occasionally be provided (87% and 80%, respectively; P = .16). Majorities of patients, nurses, and physicians endorsed the appropriateness of eight examples of SC (averages, 78%, 93%, and 87%, respectively; P = .01). In adjusted analyses, the strongest predictor of SC provision by nurses and physicians was reception of SC training (odds ratio [OR] = 11.20, 95% CI, 1.24 to 101; and OR = 7.22, 95% CI, 1.91 to 27.30, respectively). Most nurses and physicians had not received SC training (88% and 86%, respectively; P = .83).Patients, nurses, and physicians view SC as an important, appropriate, and beneficial component of EOL care. SC infrequency may be primarily due to lack of training, suggesting that SC training is critical to meeting national EOL care guidelines.
Interleukin-7 improves T-cell recovery after experimental T-cell–depleted bone marrow transplantation in T-cell–deficient mice by strong expansion of recent thymic emigrants
Authors: Annoek E. C. Broers, Sandra J. Posthumus-van Sluijs, Hergen Spits, Bronno van der Holt, Bob Löwenberg, Eric Braakman, Jan J. Cornelissen
Journal: Blood (2003)
Cardiotrophic Effects of Protein Kinase C ε
Authors: Daria Mochly-Rosen, Guangyu Wu, Harvey Hahn, Hanna Osinska, Tamar Liron, John N. Lorenz, Atsuko Yatani, Jeffrey Robbins, Gerald W. Dorn
Journal: Circulation Research (2000)

Abstract —Protein kinase C (PKC) is a key mediator of many diverse physiological and pathological responses. Although little is known about the specific in vivo roles of the various cardiac PKC isozymes, activation-induced translocation of PKC is believed to be the primary determinant of isozyme-specific functions. Recently, we have identified a catalytically inactive peptide translocation inhibitor (εV1) and translocation activator (ψεRACK [ r eceptors for a ctivated C k inase]) specifically targeting PKCε. Using cardiomyocyte-specific transgenic expression of these peptides, we combined loss- and gain-of-function approaches to elucidate the in vivo consequences of myocardial PKCε signaling. As expected for a PKCε RACK binding peptide, confocal microscopy showed that εV1 decorated cross-striated elements and intercalated disks of cardiac myocytes. Inhibition of cardiomyocyte PKCε by εV1 at lower expression levels upregulated α–skeletal actin gene expression, increased cardiomyocyte cell size, and modestly impaired left ventricular fractional shortening. At high expression levels, εV1 caused a lethal dilated cardiomyopathy. In contrast, enhancement of PKCε translocation with ψεRACK resulted in selectively increased β myosin heavy chain gene expression and normally functioning concentric ventricular remodeling with decreased cardiomyocyte size. These results identify for the first time a role for PKCε signaling in normal postnatal maturational myocardial development and suggest the potential for PKCε activators to stimulate “physiological” cardiomyocyte growth.
MANAGEMENT OF THE CHILD WITH EARLY INFANTILE AUTISM
Authors: JEROME L. SCHULMAN
Journal: American Journal of Psychiatry (1963)

We have reviewed the theoretical orientation, diagnostic criteria and management of early infantile autism at Children's Memorial Hospital. Brief reports of 8 cases were included, primarily to demonstrate the progress that may occur. We believe that many cases of early infantile autism spontaneously and gradually emerge from their difficulties and that the treatment tasks are those of encouraging and removing obstacles from this emergence.
Association between Serum Lipids and Survival in Hemodialysis Patients and Impact of Race
Authors: Ryan D Kilpatrick, Charles J McAllister, Csaba P Kovesdy, Stephen F Derose, Joel D Kopple, Kamyar Kalantar-Zadeh
Journal: Journal of the American Society of Nephrology (2006)

Despite the enormous cardiovascular disease epidemic among maintenance hemodialysis (MHD) patients, total hypercholesterolemia seems paradoxically to be associated with better survival. It was hypothesized that similar paradoxic associations also exist for serum LDL, HDL, and triglycerides. A 3-yr (July 2001 through June 2004) cohort of 15,859 MHD patients was studied in the United States from DaVita dialysis clinics where lipid profile was measured in at least 50% of all outpatients during a given calendar quarter. Cox proportional hazard models were adjusted for case mix and surrogates of malnutrition-inflammation complex. Both total and LDL hypercholesterolemia showed a paradoxic association with better survival. Hypertriglyceridemia (&gt;200 mg/dl) also showed a similar trend, but serum HDL cholesterol did not have any clear association with survival. The association between a low serum LDL &lt;70 mg/dl, which was prevalent among almost 50% of all MHD patients, and a higher all-cause death risk was robust to multivariate adjustment. In the subgroup analyses, these paradoxic associations persisted among most subgroups, although they tended to be stronger among hypoalbuminemic (&lt;3.8 mg/dl) patients and those with a lower dietary protein intake (&lt;1 g/kg per d). However, in black patients, a high serum LDL (&gt;100 mg/ml) was associated with adjusted cardiovascular death hazard ratio of 1.94 (95% confidence interval 1.12 to 2.38; <i>P</i> = 0.02). Despite inverse associations between hyperlipidemia and survival, black MHD patients with high LDL show almost two-fold increase in cardiovascular death risk. Although these associations may not be causal, they call into question whether specific subgroups of dialysis patients are better targets for cholesterol-lowering therapy.
US doctors and public favour annual check ups
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Most primary care doctors in the United States and their patients want annual physical examinations to screen for asymptomatic problems, a study has found. However, evidence based guidelines from national organisations recommend a more selective approach. Primary care doctors also say that annual check ups may build a relationship.

A study published in the Archives of Internal Medicine (2005;165:1347-52) found that two thirds of doctors in internal medicine, family practice, and …
Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group.
Authors: R Zittoun, S Suciu, F Mandelli, T de Witte, J Thaler, P Stryckmans, M Hayat, M Peetermans, M Cadiou, G Solbu, M C Petti, R Willemze
Journal: Journal of Clinical Oncology (1996)

PURPOSE To assess the value of granulocyte-macrophage colony-stimulating factor (GM-CSF) for induction treatment of acute myeloid leukemia (AML), both for priming of leukemic cells and for acceleration of hematopoietic recovery. PATIENTS AND METHODS GM-CSF was administered 5 micrograms/kg/d by continuous intravenous (i.v.) infusion during induction therapy with daunorubicin (DNR) (days 1 to 3) and cytarabine (ARA-C) (days 1 to 7). A total of 102 patients were randomized onto four arms, as follows: (1) GM-CSF 24 hours before and during chemotherapy (arm +/-); (2) GM-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes (PMNs) (arm -/+);(3) GM-CSF before, during, and after chemotherapy (arm +/+); or (4) no GM-CSF (arm -/-). Stopping rules were applied in case of an initial WBC count greater than 30 x 10(9)/L or a secondary increase of circulating blast cells. Analyses were performed according to the intention-to-treat principle. RESULTS The complete remission (CR) rates were 77% (arm -/-), 72% (arm +/-), 48% (arm -/+), and 46% (arm +/+). Patients randomized to receive GM-CSF after induction (arms -/+ and +/+) had a significantly lower CR rate (P = .008) and a trend toward accelerated recovery of neutrophils, but no fewer infections or induction deaths. The lower CR rate appeared to be related to an increased resistance rate, with persistent leukemia. The main side effects of GM-CSF were fluid retention and hypotension. CONCLUSION GM-CSF administered during induction treatment of AML with a DNR/Ara-C combination did not provide any clinical benefit. Furthermore, there was a significant decrease in the CR rate with more persistent leukemia when GM-CSF was administered during the hypoplastic phase after the chemotherapy courses.
Phosphodiesterase 4 (PDE4) regulation of proinflammatory cytokine and chemokine release from rheumatoid synovial membrane
Authors: Anne Crilly, Susan E Robertson, James H Reilly, J Alastair Gracie, Wen-Qi Lai, Bernard P Leung, Paul F Life, Iain B McInnes
Journal: Annals of the Rheumatic Diseases (2011)

Background The cAMP-metabolising enzyme, phosphodiesterase 4 (PDE4), has been implicated in a number of immune responses, including tumour necrosis factor α (TNFα) production. To date, few data have directly addressed whether synovial cytokine and chemokine production is modified by PDE4. Objective Using specific PDE4 inhibitors, roflumilast plus two novel inhibitors, INH 0061 and INH 0062, the authors studied the effect of PDE4 inhibition on proinflammatory cytokine and chemokine release from primary rheumatoid arthritis (RA) synovial digest suspensions and in a macrophage T cell co-culture assay system. Results All PDE4 inhibitors dose-dependently reduced the release of TNFα from primary synovial membrane cultures (n=5), half maximal inhibitory concentration (IC 50 ) 300–30 nM, p&lt;0.05. Similarly, a significant suppression in the release the proinflammatory chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β (IC 50 300–30 nM) and regulated upon activation normal T-cell expressed and secreted (RANTES) (IC 50 3 nM) was also observed, p&lt;0.05. While interleukin 1β was also reduced, it did not achieve an IC 50 . These observations were further confirmed in a macrophage T cell co-culture system, demonstrating the importance of PDE4 pathways in regulating cytokine/chemokine release in a cellular interaction implicated in inflammatory synovitis. Subsequent studies using the human monocytic cell line U937 also demonstrated cytokine regulation with PDE4 knockdown utilising a small interfering RNA approach. Conclusion These data provide direct evidence of PDE4-dependent pathways in human RA synovial inflammatory cytokine and chemokine release and may provide a novel approach in treating chronic autoimmune conditions such as RA.
Effects of Alcohol Dependence Comorbidity and Antipsychotic Medication on Volumes of the Thalamus and Pons in Schizophrenia
Authors: Edith V Sullivan, Margaret J Rosenbloom, Kathleen L Serventi, Anjali Deshmukh, Adolf Pfefferbaum
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Postmortem and in vivo brain imaging studies have identified abnormalities in the thalamus and the pons in both schizophrenia and alcoholism. The authors sought to determine whether patients with both schizophrenia and alcohol dependence would manifest exaggerated volume deficits in either structure. METHOD: Volumetric measures of the left and right thalamus and the pons were derived from magnetic resonance imaging scans obtained from 27 patients with schizophrenia, 19 patients with schizophrenia and comorbid alcohol dependence, 25 patients with alcohol dependence without comorbid axis I disorders, and 51 healthy comparison subjects. RESULTS: The alcohol-dependent patients had significant volume deficits in both the thalamus and the pons. Among patients with schizophrenia, there were no differences in thalamus volumes between those with and without comorbid alcohol dependence. However, patients with schizophrenia who were taking atypical antipsychotic medications had bilateral thalamic deficits, whereas those taking typical neuroleptics did not. Patients with schizophrenia and comorbid alcohol dependence had deficits in the pons. CONCLUSIONS: Patients with schizophrenia and comorbid alcohol dependence are at risk for alcohol-related reduction of pontine structures that are not necessarily affected by schizophrenia per se. The effect of alcohol dependence on the thalamus in schizophrenic patients may be mitigated by the type of neuroleptic medication they receive.