tbuckley/cabot-search huggingface dataset:
Effects of norepinephrine on expression of IGF-1/IGF-1R and SERCA2 in rat heart
Authors: XiWu Sun, Yuk-Chow Ng
Journal: Cardiovascular Research (1998)

The effects of norepinephrine on expression of cardiac genes during pathological cardiac growth and heart failure are not fully understood. Tissue insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) play an important role in the regulation of the hyperplastic capacity of cardiac myocytes. Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2), on the other hand, is important in regulating cardiac contractile function. The present study examined the effects of elevated levels of NE on expression of IGF-1/IGF-1R and SERCA2 mRNAs.Rats were infused with NE using osmotic minipumps for 3 and 6 days at a rate of 50 micrograms/kg/h and also at a higher dose (130 micrograms/kg/h) for 6 and 14 days. Levels of expression of IGF-1/IGF-1R and SERCA2 mRNAs were determined by ribonuclease protection assay and by Northern blotting, respectively.NE treatment significantly increased IGF-1 mRNA levels in both left- and right-ventricle; however, levels of IGF-1R increased in the left- but not the right-ventricle. By contrast, NE infusion at both the lower dose and the higher dose failed to alter expression of SERCA2 mRNA.Our results suggest that NE treatment differentially regulates expression of IGF-1 and IGF-1R in the ventricles of rat heart and that NE appears not to affect expression of SERCA2 mRNA.
Nuclear Factor-κB Modulation in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia
Authors: Roger K. Strair, Mecide Gharibo, Dale Schaar, Arnold Rubin, Jonathan Harrison, Joseph Aisner, Hsin-Ching Lin, Yong Lin, Lauri Goodell, Monika Anand, Binaifer Balsara, Liesel Dudek, Arnold Rabson, Daniel J. Medina
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Nuclear factor-κB (NF-κB) is constitutively expressed in many acute myelogenous leukemia (AML) cells and AML stem cells. Ex vivo treatment of AML cells with inhibitors of NF-κB results in diminished AML cell survival and enhances the cytotoxic effects of chemotherapeutic agents. The purpose of this study was to determine if standard anti-inflammatory agents modulate AML cell nuclear NF-κB when administered in conjunction with induction chemotherapy. Experimental Design: Patients with newly diagnosed AML were treated with dexamethasone, choline magnesium trisalicylate, or both for 24 hours prior to and 24 hours following initiation of standard induction chemotherapy. AML cell nuclear NF-κB was measured at baseline, 24, and 48 hours. Results: Choline magnesium trisalicylate ± dexamethasone decreased nuclear NF-κB, whereas dexamethasone alone was associated with an increase in nuclear NF-κB in AML cells. Conclusions: These results show the feasibility of NF-κB modulation in conjunction with induction chemotherapy for patients with AML using inexpensive readily available medications. A follow-up study to determine the effects of NF-κB modulation on clinical end points is warranted.
The Interferon Signaling Antagonist Function of Yellow Fever Virus NS5 Protein Is Activated by Type I Interferon
Authors: Maudry Laurent-Rolle, Juliet Morrison, Ricardo Rajsbaum, Jesica M. Levingston Macleod, Giuseppe Pisanelli, Alissa Pham, Juan Ayllon, Lisa Miorin, Carles Martínez-Romero, Benjamin R. tenOever, Adolfo García-Sastre
Journal: Cell Host & Microbe (2014)
Trusts ignoring safety alerts should be named, says CMO
Authors: Adrian O'Dowd
Journal: BMJ (2005)

The chief medical officer, Liam Donaldson, has called for details to be made public of NHS organisations that fail to comply with alerts concerning patients' safety.

Launching his annual report last week, he said the NHS was failing in this area of health and specifically called on the Healthcare Commission to pay special attention to compliance with safety alerts. He also called for a national group to be established to review the effect of safety alerts …
The Facilitated Values History
Authors: Leslie P. Scheunemann, Robert M. Arnold, Douglas B. White
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Section:ChooseTop of pageAbstract <<Autonomous Decisions or A...Values in Tension Near th...The Facilitated Values Hi...Limitations of the Facili...Strengths of the Facilita...Potential Criticisms of t...ConclusionsReferencesCITING ARTICLES
Characterisation of anticytoplasmic antibodies and their clinical associations.
Authors: W.H. Koh, J Dunphy, J Whyte, J Dixey, N.J. McHugh
Journal: Annals of the Rheumatic Diseases (1995)

To characterise the cytoplasmic staining patterns identified by indirect immunofluorescence (IF) of human epithelial (HEp-2) cells and the antigens recognised using additional serological techniques. To define the disease associations of anticytoplasmic antibodies. Sera from 1173 patients were screened for cytoplasmic IF staining on HEp-2 cells and the patterns characterised. The presence of antimitochondrial antibodies (AMA) was evaluated by a sensitive anti-pyruvate dehydrogenase complex enzyme linked immunosorbent assay (ELISA) (IgG) and by immunoblotting. Detection of antibodies to extractable nuclear antigens (ENA) was performed by double immunodiffusion and the presence of anti-ribosomal P antibodies was determined by immunoblotting. Cytoplasmic IF staining was demonstrated in 75 sera (6.4%). Six different patterns were recognised: coarse granular filamentous speckles (AMA, n = 9); condensed large speckles (anti-golgi apparatus antibodies, n = 3); cytoskeletal (n = 9); centriolar (n = 4); diffuse coarse speckles (n = 33); and fine speckles (n = 17). Of the nine sera with an AMA pattern, the presence of these antibodies was confirmed in seven by the ELISA (n = 6) and on immunoblotting (n = 7). One of the seven patients had primary biliary cirrhosis, and two had scleroderma. Two patients with anti-golgi antibodies had rheumatoid arthritis and two with anticentriolar antibodies had scleroderma. Of 33 sera that had cytoplasmic staining and were ANA negative, three were positive for anti-Ro and two were positive for anti-Jo-1 antibodies. In general, defined cytoplasmic IF patterns have no specific disease associations. However, the finding of cytoplasmic fluorescence should not be ignored, as it may indicate the presence of antibodies to ENA in the absence of nuclear staining.
Chronic Renal Failure after Transplantation of a Nonrenal Organ
Authors: Akinlolu O. Ojo, Philip J. Held, Friedrich K. Port, Robert A. Wolfe, Alan B. Leichtman, Eric W. Young, Julie Arndorfer, Laura Christensen, Robert M. Merion
Journal: New England Journal of Medicine (2003)

Transplantation of nonrenal organs is often complicated by chronic renal disease with multifactorial causes. We conducted a population-based cohort analysis to evaluate the incidence of chronic renal failure, risk factors for it, and the associated hazard of death in recipients of nonrenal transplants.Pretransplantation and post-transplantation clinical variables and data from a registry of patients with end-stage renal disease (ESRD) were linked in order to estimate the cumulative incidence of chronic renal failure (defined as a glomerular filtration rate of 29 ml per minute per 1.73 m2 of body-surface area or less or the development of ESRD) and the associated risk of death among 69,321 persons who received nonrenal transplants in the United States between 1990 and 2000.During a median follow-up of 36 months, chronic renal failure developed in 11,426 patients (16.5 percent). Of these patients, 3297 (28.9 percent) required maintenance dialysis or renal transplantation. The five-year risk of chronic renal failure varied according to the type of organ transplanted - from 6.9 percent among recipients of heart-lung transplants to 21.3 percent among recipients of intestine transplants. Multivariate analysis indicated that an increased risk of chronic renal failure was associated with increasing age (relative risk per 10-year increment, 1.36; P<0.001), female sex (relative risk among male patients as compared with female patients, 0.74; P<0.001), pretransplantation hepatitis C infection (relative risk, 1.15; P<0.001), hypertension (relative risk, 1.18; P<0.001), diabetes mellitus (relative risk, 1.42; P<0.001), and postoperative acute renal failure (relative risk, 2.13; P<0.001). The occurrence of chronic renal failure significantly increased the risk of death (relative risk, 4.55; P<0.001). Treatment of ESRD with kidney transplantation was associated with a five-year risk of death that was significantly lower than that associated with dialysis (relative risk, 0.56; P=0.02).The five-year risk of chronic renal failure after transplantation of a nonrenal organ ranges from 7 to 21 percent, depending on the type of organ transplanted. The occurrence of chronic renal failure among patients with a nonrenal transplant is associated with an increase by a factor of more than four in the risk of death.
Interaction between social influence and payoff transparency
Authors: Xinyue Zhou, Wenwen Xie, Maolin Ye
Journal: Behavioral and Brain Sciences (2014)

Abstract Social influence and payoff transparency interact with each other to influence decision making. Social influence masks payoff transparency, and lacking transparency drives people to seek social influence. Moreover, our survey supports our claim by showing that social influence and payoff transparency correlate with each other ( r (53) = –.71). Bentley et al.’s model can be revised to accommodate the covariance.
Hepatitis C virus infection and needle exchange use among young injection drug users in San Francisco
Authors: Judith A. Hahn, Kimberly Page-Shafer, Paula J. Lum, Kristen Ochoa, Andrew R. Moss
Journal: Hepatology (2001)

Young injection drug users (IDUs) in San Francisco may be at high risk for hepatitis C virus (HCV) infection despite access to several needle exchange venues. The authors conducted a cross–sectional study from 1997 to 1999 in San Francisco to estimate the prevalence and incidence of antibody to HCV (anti–HCV) among street–recruited IDUs under age 30, and to examine risk behaviors and sources of sterile needles. Among 308 participants, the prevalence of anti–HCV was 45%. Using statistical modeling, incidence of HCV infection was estimated to be 11 per 100 person years. Independent risk factors for anti–HCV included age (odds ratio [OR], 1.17 per year; 95% confidence interval [CI], 1.05–1.30), years injecting (OR, 1.21 per year; 95% CI, 1.10–1.34), years in San Francisco (OR, 1.06 per year; 95% CI, 1.00–1.14), first injected by a sex partner (OR, 4.06; 95% CI, 1.74–9.52), injected daily (OR, 3.85; 95% CI, 2.07–7.17), ever borrowed a needle (OR, 2.56; 95% CI, 1.18–5.53), bleached last time a needle was borrowed (OR, 0.50; 95% CI, 0.24–1.02), snorted or smoked drugs in the prior year (OR, 0.48; 95% CI, 0.26–0.89), and injected by someone else in the prior month (OR, 0.50; 95% CI, 0.25–0.99). In the prior month, 88% used at least 1 of several needle exchange venues, and 32% borrowed a needle. We conclude that anti–HCV prevalence is lower than in previous studies of older IDUs, but 11% incidence implies high risk of HCV infection in a long injecting career. Despite access to sterile needles, borrowing of needles persisted.
Does malnutrition affect survival in cirrhosis?
Authors: M Merli
Journal: Hepatology (1996)

A total of 1,053 cirrhotic patients were included in a prospective study to determine whether malnutrition is a risk factor for mortality in cirrhotic patients. Child-Pugh classification as well as clinical and biochemical variables were used to assess the severity of cirrhosis. Nutritional status was evaluated both by anthropometric and clinical measurements. Patients were defined as malnourished when midarm muscle area (MAMA) and/or midarm fat area (MAFA) were below the 5th percentile of an age- and sex-matched population. During follow-up, 419 patients died. The estimated survival rate was 82.7% at 1 year, 65.1% at 3 years, and 50.7% at 5 years. The presence of muscle depletion and/or of a steep reduction in fat deposits was associated with a higher risk of mortality (midarm muscle area, < 5th percentile, relative risk = 1.79; midarm fat area, < 5th percentile, relative risk = 1.35). When patients were stratified according to the Child-Pugh classification, cumulative survival was lower in patients with a reduction in muscle mass in Child-Pugh classes A and B (log rank: P = .027; P = .022, respectively) but not in class C. Conversely, a significant reduction in adipose tissue deposits appeared to have no independent impact on survival in any Child-Pugh class. When examined using a multivariate Cox proportional hazard analysis, age, sex, bilirubin, cholinesterase, ascites, and esophageal varices were selected, whereas the parameters of nutritional status were not. This suggests that malnutrition, while strongly associated with the deterioration of liver function, cannot be considered an independent risk factor for mortality in a general population of cirrhotic patients.
Great toe-nail dystrophy
Authors: T.A.J. Dawson, R. Baran
Journal: British Journal of Dermatology (1989)

Journal Article Great toe‐nail dystrophy Get access T.A.J. Dawson, T.A.J. Dawson Department of Dermatology, Craigavon Area Hospital, Craigavon BT63 5QQ, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. Baran R. Baran Dermatology Unit, Cannes General Hospital, 04600 Cannes, France. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 120, Issue 1, 1 January 1989, Pages 139–140, https://doi.org/10.1111/j.1365-2133.1989.tb07776.x Published: 01 January 1989
Pharmacological postconditioning effect of muramyl dipeptide is mediated through RIP2 and TAK1
Authors: P. Sicard, S. Jacquet, K. S. Kobayashi, R. A. Flavell, M. S. Marber
Journal: Cardiovascular Research (2009)

Despite their ability to cause septic shock and myocardial dysfunction, components of Gram-negative bacterial cell walls, like lipopolysaccharide, have been shown in numerous studies to induce myocardial protection during ischaemia–reperfusion injury. Muramyl dipeptide (MDP) is another such component recognized by an intracellular receptor, nucleotide-binding oligomerization domain 2. Receptor activation leads to intracellular signals through receptor interacting protein-2 (RIP2) and tumour growth factor-β-activated kinase-1 (TAK1). However, little is known about the RIP2/TAK1 pathway in the heart. The aim of this study was to determine whether the RIP2/TAK1 pathway has a cardioprotective role in a mouse model of myocardial infarction. We isolated and subjected wild-type (WT) and RIP2−/− mouse hearts to 30 min of global ischaemia and 120 min of reperfusion with or without perfusion of MDP (10 µg/mL) before or after the ischaemic period and determined the infarct size. We examined activation of the TAK1/nuclear factor κB (NFκB) signalling pathway. The effect of TAK1 inhibition on MDP-induced cardioprotection was also evaluated. Exposure to MDP during reperfusion significantly reduced infarct size in WT hearts (from 51.7 ± 5.6% in control to 38.1 ± 6.7%, P < 0.05), but not in RIP2−/− hearts or in WT hearts with coincident pharmacological inhibition of TAK1. MDP treatment significantly increased the levels of p-TAK1 and p-JNK (Jun N-terminal kinase) and led to NFκB activation via phosphorylation and degradation of IkappaB in the WT, but not in the RIP2−/−, myocardium. These results indicate that MDP at reperfusion induced cardioprotection through an RIP2/TAK1-dependent mechanism.
Guinea pig immune response-related histocompatibility antigens. Partial characterization and distribution.
Authors: F D Findelman, E M Shevach, E S Vitetta, I Green, W E Paul
Journal: The Journal of Experimental Medicine (1975)

We have previously demonstrated that guinea pig alloantisera directed at strain 2 and strain 13 membrane antigens block specific lymphocyte activation in immune response gene-controlled systems. In this communication we describe the partial characterization of the antigens against which these antisera are directed (the 2 and 13 antigens) and, in addition, that of the B antigen which by distribution resembles the human HL-A and mouse H-2 major histocompatibility antigens. Lymphoid cells from strain 2 and strain 13 guinea pigs were surface labeled with 125I by the lactoperoxidase technique. Nonidet P-40 extracts of these labeled cells were precipitated by sandwiches of strain 2 antistrain 13, strain 13 antistrain 2, or outbred anti-B antisera, followed by rabbit antiguinea pig immunoglobulin antisera. Precipitates were dissolved in sodium dodecyl sulfate (SDS) and electrophoresed on SDS polyacrylamide gels. Radioactive peaks representing the 2 and B-cell membrane antigens were obtained from strain 2 lymph node cells, as well as from a B-lymphoid cell population (L2C leukemia cells) and a T-lymphocyte population (STRAIN 2 PERITONEAL EXUDATE LYMPHOCYTES [PELs]). Radioactive peaks representing the 13 and B-cell membrane antigens were obtained from strain 13 lymph node cells and strain 13 PELs. All anti-B precipitates produced two peaks when electrophoresed on SDS polyacrylamide gels; one representing an antigen with a mol wt of approximately 45,000, and one representing an antigen with a mol wt of about 12,000. Both may be components of a single protein. All anti-2 and anti-13 precipitates produced a single peak when electrophoresed on SDS polyacrylamide gels. Both the 2 and 13 antigens were found by this technique to have mol wt of approximately 25,000. By molecular weight criteria, as well as by previously investigated distributional criteria, the B antigen is similar to the human LA and Four antigens, and to the mouse D and K antigens, and the 2 and 13 antigens are similar to the mouse Ia antigens.
Effects of eicosapentaenoic acid on cardiac SR Ca2+-release and ryanodine receptor function
Authors: J Swan
Journal: Cardiovascular Research (2003)

n-3 polyunsaturated fatty acids (PUFAs) can prevent life-threatening arrhythmias but the mechanisms responsible have not been established. There is strong evidence that part of the antiarrhythmic action of PUFAs is mediated through inhibition of the Ca2+-release mechanism of the sarcoplasmic reticulum (SR). It has also been shown that PUFAs activate protein kinase A (PKA) and produce effects in the cardiac cell similar to β-adrenergic stimulation. We have investigated whether the inhibitory effect of PUFAs on the Ca2+-release mechanism is caused by direct inhibition of the SR Ca2+-release channel/ryanodine receptor (RyR) or requires activation of PKA. Experiments in intact cells under voltage-clamp show that the n-3 PUFA eicosapentaenoic acid (EPA) is able to reduce the frequency of spontaneous waves of Ca2+-release while increasing SR Ca2+ content even when PKA activity is inhibited with H-89. This suggests that the EPA-induced inhibition of SR Ca2+-release is not dependent on activation of PKA. Consistent with this, single-channel studies demonstrate that EPA (10–100 μM), but not saturated fatty acids, reduce the open probability (Po) of the cardiac RyR incorporated into phospholipid bilayers. EPA also inhibited the binding of [3H]ryanodine to isolated heavy SR. Our results indicate that direct inhibition of RyR channel gating by PUFAs play an important role in the overall antiarrhythmic properties of these compounds.
Effect of chronic renal failure on Ca2+ ATPase of brain synaptosomes.
Authors: S M Hajjar, M Smogorzewski, M A Zayed, G Z Fadda, S G Massry
Journal: Journal of the American Society of Nephrology (1991)

Chronic renal failure (CRF) is associated with a sustained rise in the concentration of cytosolic calcium [( Ca2+]i) of brain synaptosomes. This was attributed to secondary hyperparathyroidism where the excess blood levels of parathyroid hormone (PTH) augment calcium entry into synaptosomes. However, for such an effect of PTH to cause a sustained rise in [Ca2+]i, calcium extrusion out of synaptosomes should be impaired. The study presented here examined the effect of CRF with and without (CRF-PTX) excess PTH and the treatment of CRF rats with verapamil (V) on the Vmax and Km for calcium of synaptosomal Ca2+ ATPase, an enzyme that plays an important role in pumping calcium out of the synaptosomes. The Vmax of synaptosomal Ca2+ ATPase in CRF rats was significantly (P less than 0.01) lower than that of normal, CRF-PTX, CRF-V, and normal-V rats. However, the values in CRF-V were still below normal (P less than 0.05). There were no significant differences in the Km for calcium of synaptosomal Ca2+ ATPase among the five groups of animals. [Ca2+]i was significantly (P less than 0.01) higher in synaptosomes of CRF rats than in normal, CRF-PTX, CRF-V, and normal-V animals, and the values among the latter four groups were not different. The data demonstrate that the activity of synaptosomal Ca2+ ATPase is reduced in CRF rats, and this derangement is related to the excess PTH. This derangement in Ca2+ ATPase activity plays an important role in the genesis of the sustained elevation of synaptosomal [Ca2+]i in CRF.
LEUKOCYTE-DEPENDENT HISTAMINE RELEASE FROM RABBIT PLATELETS
Authors: Jacques Benveniste, Peter M. Henson, Charles G. Cochrane
Journal: The Journal of Experimental Medicine (1972)

We have studied the leukocyte-dependent mechanism of histamine release (LDHR) from rabbit platelets, a complement-independent mechanism which has been implicated in the deposition of immune complexes in acute serum sickness of rabbits. It was found by chromatography and passive transfer of serum from immunized rabbits that the antibody responsible for the LDHR was of IgE type. By electron microscope study of the reaction, the leukocyte involved in agglutination of platelets and release of their histamine content was identified as the basophil. Upon addition of antigen, basophils sensitized with IgE degranulated, released their histamine content and a platelet-activating factor (PAF) that caused aggregation of platelets and release of their histamine. Conditions of preparing and preserving PAF activity and some properties of this factor have been elucidated. LDHR must, therefore, be considered as an immediate hypersensitivity-type mechanism which may link allergic reactions with immunologic disease associated with severe structural injury.
Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial
Authors: Dorien C Rijkaart, Johannes Berkhof, Lawrence Rozendaal, Folkert J van Kemenade, Nicole WJ Bulkmans, Daniëlle AM Heideman, Gemma G Kenter, Jack Cuzick, Peter JF Snijders, Chris JLM Meijer
Journal: The Lancet Oncology (2011)
Molecular Basis of Environmentally Induced Birth Defects
Authors: Richard H. Finnell, Janée Gelineau-van Waes, James D. Eudy, Thomas H. Rosenquist
Journal: The Annual Review of Pharmacology and Toxicology (2002)

Exposure of the developing conceptus to selected environmental agents can lead to deleterious and often times lethal birth defects. These malformations result in serious emotional and financial consequences to families and societies worldwide. As we continue to progress technologically, we face challenges from the introduction of new pharmacological agents and chemical compounds into the environment. This results in a concomitant need to more fully understand the relationship between in utero exposure to environmental teratogens and the risk of congenital malformations. The goal of this review is to provide a current perspective of the major concepts related to the molecular basis of environmentally induced birth defects. Starting with a discussion of commonly occurring birth defects, we consider important fundamental facets of embryonic development, teratology, and gene-environment interactions. The review then summarizes our current understanding of the molecular mechanisms involved in selected birth defects following exposure to pharmacological compounds, including thalidomide, retinoids, and valproic acid. Understanding these signaling pathways may lead to the development of safer pharmaceutical compounds and a reduction in the number of infants born with preventable birth defects.