tbuckley/cabot-search huggingface dataset:
MicroRNA-95 Promotes Cell Proliferation and Targets Sorting Nexin 1 in Human Colorectal Carcinoma
Authors: Zhaohui Huang, Shenglin Huang, Qifeng Wang, Linhui Liang, Shujuan Ni, Lisha Wang, Weiqi Sheng, Xianghuo He, Xiang Du
Journal: Cancer Research (2011)

MicroRNAs (miRNAs) are strongly implicated in cancer but their specific roles and functions in the major cancers have yet to be fully elucidated. In this study, we defined the oncogenic significance and function of miR-95, which we found to be elevated in colorectal cancer (CRC) tissues by microarray analysis. Evaluation of an expanded CRC cohort revealed that miR-95 expression was up-regulated in nearly half of the tumors examined (42/87) compared with the corresponding noncancerous tissues. Ectopic overexpression of miR-95 in human CRC cell lines promoted cell growth in vitro and tumorigenicity in vivo, whereas RNAi-mediated silencing of miR-95 decreased cell growth ratio. Mechanistic studies revealed that miR-95 repressed the expression of reporter gene coupled to the 3'-untranslated region of sorting nexin 1 (SNX1), whereas miR-95 silencing up-regulated SNX1 expression. Moreover, miR-95 expression levels correlated inversely with SNX1 protein levels in human CRC tissues. RNAi-mediated knockdown of SNX1 phenocopied the proliferation-promoting effect of miR-95, whereas overexpression of SNX1 blocked miR-95-induced proliferation of CRC cells. Taken together, these results demonstrated that miR-95 increases proliferation by directly targeting SNX1, defining miR-95 as a new oncogenic miRNA in CRC.
3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Increase Fibrinolytic Activity in Rat Aortic Endothelial Cells
Authors: Marie Essig, Geneviève Nguyen, Dominique Prié, Brigitte Escoubet, Jean-Daniel Sraer, Gérard Friedlander
Journal: Circulation Research (1998)

Abstract —3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (HRIs) have been recently shown to prevent atherosclerosis progression. Clinical benefit results from combined actions on various components of the atherosclerotic lesion. This study was designed to identify the effects of HRI on one of these components, the endothelial fibrinolytic system. Aortas isolated from rats treated for 2 days with lovastatin (4 mg/kg body wt per day) showed a 3-fold increase in tissue plasminogen activator (tPA) activity. In a rat aortic endothelial cell line (SVARECs) and in human nontransformed endothelial cells (HUVECs), HRI induced an increase in tPA activity and antigen in a time- and concentration-dependent manner. In SVARECs, the maximal response was observed when cells were incubated for 48 hours with 50 μmol/L HRI. An increase of tPA mRNA was also in evidence. In contrast, HRI inhibited plasminogen activator inhibitor-1 activity and mRNA. The effects of HRI were reversed by mevalonate and geranylgeranyl pyrophosphate, but not by LDL cholesterol and farnesyl pyrophosphate, and were not induced by α-hydroxyfarnesyl phosphonic acid, an inhibitor of protein farnesyl transferase. C3 exoenzyme, an inhibitor of the geranylgeranylated-activated Rho protein, reproduced the effect of lovastatin on tPA and plasminogen activator inhibitor-1 activity and blocked its reversal by geranylgeranyl pyrophosphate. The effect of HRI was associated with a disruption of cellular actin filaments without modification of microtubules. A disrupter of actin filaments, cytochalasin D, induced the same effect as lovastatin on tPA, whereas a disrupter of microtubules, nocodazole, did not. In conclusion, HRI can modify the fibrinolytic potential of endothelial cells, likely via inhibition of geranylgeranylated Rho protein and disruption of the actin filaments. The resulting increase of fibrinolytic activity of endothelial cells may contribute to the beneficial effects of HRI in the progression of atherosclerosis.
Stimulus-response curve of the renal baroreceptor: effect of converting enzyme inhibition and changes in salt intake.
Authors: E R Farhi, J R Cant, W C Paganelli, V J Dzau, A C Barger
Journal: Circulation Research (1987)

We investigated the effect of converting enzyme inhibition (CEI) on the relationship between renal perfusion pressure (RPP) and steady-state plasma renin activity (PRA) in uninephrectomized conscious dogs on normal-salt (80 meq Na+/day) and low-salt (10 meq Na+/day) diets. Stimulus-response curves for the renal baroreceptor were determined by measuring the steady-state PRA while the RPP was lowered and then held constant by an inflatable cuff placed around the renal artery. On each diet the control stimulus-response curve can be described by two lines intersecting at a threshold pressure; in the higher pressure range PRA is relatively insensitive to changes in RPP, while in the lower pressure range PRA is very responsive to changes in RPP. On the normal-salt diet CEI significantly increases the sensitivity of PRA to RPP in the responsive range without affecting the threshold pressure itself or the values of PRA at pressures greater than the threshold pressure. On the low-salt diet CEI also increases the sensitivity of PRA to RPP significantly in the responsive range; we were unable to determine the effect of CEI on PRA at RPPs greater than the threshold pressure in the low-salt state because CEI causes a significant drop in blood pressure under these circumstances. The effect of CEI was significantly greater in the dogs on the low-salt diet than in the dogs on the normal-salt diet. Thus, CEI and salt depletion interact synergistically to increase the sensitivity of the renal baroreceptor only in the responsive range of the stimulus-response curve, i.e., at renal perfusion pressures below the threshold pressure.
Postembryonic Neuronal Plasticity and its Hormonal Control During Insect Metamorphosis
Authors: J C Weeks, R B Levine
Journal: Annual Review of Neuroscience (1990)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Effects of Cardiac Resynchronization Therapy on Myocardial Perfusion Reserve
Authors: Paul Knaapen, Linda (C.)M.C. van Campen, Carel C. de Cock, Marco J.W. Götte, Cees A. Visser, Adriaan A. Lammertsma, Frans C. Visser
Journal: Circulation (2004)

Cardiac resynchronization therapy (CRT) is a relatively new treatment strategy for patients with heart failure and mechanical asynchrony. Reported effects of CRT on regional myocardial blood flow (MBF) are conflicting, and effects on hyperemic MBF are scarce. The aim of the present study was to assess serial changes of MBF and MBF reserve in patients receiving a biventricular pacemaker.Fourteen patients with heart failure (NYHA class III or IV; left ventricular ejection fraction <35%), QRS width >120 ms, and sinus rhythm were studied (mean age, 58+/-10 years; 8 men). MBF and hyperemic MBF were measured at baseline, 3 months after biventricular pacing (CRT on), and after cessation of pacing (CRT off) with PET and H2(15)O. CRT had no significant effect on resting MBF (baseline versus CRT on versus CRT off: 0.82+/-0.25 versus 0.69+/-0.24 versus 0.74+/-0.24 mL x min(-1) x mL(-1); P=NS). Hyperemic MBF increased during CRT (1.91+/-1.03 versus 2.66+/-1.66 versus 1.92+/-1.06 mL x min(-1) x mL(-1); P=0.01 by MANOVA), as did MBF reserve (2.25+/-1.00 versus 3.76+/-2.38 versus 2.49+/-0.94 mL x min(-1) x mL(-1); P=0.023). CRT (reversibly) resulted in a more homogeneous distribution of regional resting MBF as demonstrated by the septal-to-lateral ratio. The decrease in the ratio of left ventricular end-diastolic volume to left ventricular mass, as a reflection of wall stress, was related to the increase in hyperemic MBF (r=0.53, P<0.05). Left ventricular ejection fraction increased from 25+/-7% to 37+/-9% (P<0.01).Resting MBF is unaltered by CRT despite an increase in left ventricular function. However, the distribution pattern of resting MBF becomes more homogeneous. Hyperemic MBF and consequently MBF reserve are enhanced by CRT.
Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors
Authors: Emile van den Akker, Thamar van Dijk, Martine Parren-van Amelsvoort, Katja S. Grossmann, Ute Schaeper, Kenya Toney-Earley, Susan E. Waltz, Bob Löwenberg, Marieke von Lindern
Journal: Blood (2004)
Androgen Deprivation Boosts Prostatic Infiltration of Cytotoxic and Regulatory T Lymphocytes and Has No Effect on Disease-Free Survival in Prostate Cancer Patients
Authors: Carlo Sorrentino, Piero Musiani, Paolo Pompa, Giuseppe Cipollone, Emma Di Carlo
Journal: Clinical Cancer Research (2010)

The value of neoadjuvant hormone therapy (NHT) prior to radical prostatectomy as a means of restraining prostate cancer (PCa) and strengthening its immunotherapy is still uncertain. This article asks whether it subverts immunoregulatory pathways governing tumor microenvironments, and has an impact on patient outcome.We microdissected epithelium and stroma from cancerous and normal prostate specimens from 126 prostatectomized patients, of whom 76 had received NHT, to detect cytokine/chemokine gene expression levels by real-time reverse transcriptase PCR. Confocal microscopy was used to identify cytokine/chemokine cell sources, and immunostainings to characterize lymphocyte subsets whose prognostic effects were assessed by Kaplan-Meier analyses.NHT boosted the expression of IL-7 in the stroma and that of IFNγ-inducible protein-10/CXCL10 in the glandular epithelium of normal prostate tissue, and restored the CD8(+) lymphocyte depletion occurring in PCa, whereas it significantly increased the CD4(+) lymphocyte infiltrate. Lymphocytes, mostly with CD8(+) phenotype, expressed the T-cell intracellular antigen-1, granzyme-B, and perforin, typical of cytotoxic-effector T cells. NHT also induced thymus and activation-regulated chemokine/CCL17 production by monocytes/macrophages in the prostate and draining lymph nodes, and increased the number of their Forkhead box P3 (Foxp3)(+)CD25(+)CD127(-) T regulatory (Treg) cells. The χ(2) test disclosed the lack of association (P = 0.27) between NHT and the high intratumoral CD8(+)/Treg ratio indicative of a good prognosis.Androgen withdrawal regulates cytokine/chemokine gene expression in normal prostate and lymphoid tissues, and this probably favors both CD8(+) and Treg infiltrates, leaves their intratumoral balance unchanged, and thus has no impact on disease-free survival.
Occupational asthma in newly employed workers in intensive swine confinement facilities
Authors: J.A. Dosman
Journal: European Respiratory Journal (2004)

Respiratory symptoms, reductions in pulmonary function and increased bronchial responsiveness have been described in exposed workers and in naïve volunteers exposed to intensive swine production facilities. Typically, this occurs in persons who have been employed for a long duration or in previously unexposed, naïve volunteers. The current authors describe four cases, all female, who developed acute onset of wheezing and cough suggestive of asthma within weeks of commencing full-time employment in intensive swine production facilities. None of the workers were aware of any previous asthma, allergies or hay fever. All four employees reported improvement of symptoms on cessation of work in the facilities and consequent withdrawal from exposure. However, when seen at the respiratory clinic, cases 1 and 3 continued to be either mildly symptomatic or were taking medications with continued borderline airways responsiveness, as measured by methacholine challenge test up to 4 and 5 months, respectively, following work cessation. Case 2 continued to have symptoms for > or =3 months after work cessation. Only case 1, however, was seen at repeated visits in the respiratory clinic. One worker participated in a work re-entry trial and experienced profound coughing and chest tightness within an hour of entry, after which, the trial had to be terminated. Provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20) measured 5 h later was lower than pre-trial PC20. No acute exposure event was recorded in the workers prior to the onset of symptoms. To the current authors' knowledge, this is the first report of occupational asthma occurring in newly employed full-time intensive swine production workers after a short-term exposure and should raise awareness that previously unexposed workers may be at risk of developing what would appear to be long-term asthma after relatively short-term exposure.
Characterization of a New Antibody Raised against the NH2 Terminus of P-Glycoprotein
Authors: Prema S. Rao, Rajgopal Govindarajan, Kavita B. Mallya, William West, U. Subrahmanyeswara Rao
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cancers exposed to chemotherapy develop multidrug resistance, a major cause for chemotherapy failure. One mechanism of multidrug resistance development is due to overexpression of P-glycoprotein (Pgp) in these cancer cells. Thus, a prechemotherapy evaluation of Pgp in cancer cells aids in the design of alternative regimens that can circumvent such failure. As few Pgp-specific antibodies are available in detecting low levels of Pgp, there is a need for preparing an antibody that allows the detection of Pgp by various immunologic methods. Experimental Design: We selected the amino acid stretch 11 to 34 in the cytoplasmically located NH2 terminus of Pgp as antigen, which was chemically synthesized and used to raise an antibody in a rabbit, termed NH211 antibody. We compared the properties of NH211 antibody with that of the well-characterized Pgp-specific antibody, C219, by Western blotting, immunoprecipitation, immunocytochemistry, and immunohistochemistry. Results: Immunoblotting analysis suggested that NH211 antibody efficiently interacts with both recombinant and constitutively expressed Pgp in cancerous and noncancerous human cells. Immunoprecipitation reactions indicated that the NH211 antibody selectively immunoprecipitates Pgp. Immunocytochemical analyses indicated that the NH211 antibody detects Pgp in drug-resistant breast cancer cells as well as in human prostate and breast adenocarcinoma tissue sections. Conclusion: As the NH211 antibody detects Pgp present in cells and tissues, we conclude that the amino acid sequence to which this antibody was raised is highly antigenic and the antibody is useful in the detection of Pgp by a variety of immunologic methods.
Retraction Note: Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies
Authors: Karsten Haug, Maike Warnstedt, Alexi K Alekov, Thomas Sander, Alfredo Ramírez, Barbara Poser, Snezana Maljevic, Simon Hebeisen, Christian Kubisch, Johannes Rebstock, Steve Horvath, Kerstin Hallmann, Joern S Dullinger, Birgit Rau, Fritz Haverkamp, Stefan Beyenburg, Herbert Schulz, Dieter Janz, Bernd Giese, Gerhard Müller-Newen, Peter Propping, Christian E Elger, Christoph Fahlke, Holger Lerche, Armin Heils
Journal: Nature Genetics (2009)
Limitations on current explanations of category-specific agnosia
Authors: Daniel Bub, Cindy Bukach
Journal: Behavioral and Brain Sciences (2001)

The HIT framework accepts a number of assumptions that are widely held as plausible or even well established in the literature on category-specific agnosia. We point out that a number of these elementary conjectures, now almost taken for granted, have received little in the way of convincing empirical support.
Risk of irritable bowel syndrome in first-degree, second-degree and thirddegree relatives of affected individuals: a nationwide family study in Sweden
Authors: Rasmus Waehrens, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist, Bengt Zöller
Journal: Gut (2014)

<h3>Objectives</h3> IBS aggregates in families, but the familial risk of IBS has only been determined in first-degree relatives and spouses. This nationwide study aimed to determine the familial risk of IBS in first-degree, second-degree, and third-degree relatives and spouses of affected individuals in order to estimate the relative influences of genes and shared family environment. <h3>Methods</h3> We performed a case-cohort study. The Swedish Multigeneration Register was linked to the Hospital Discharge Register for the period 1987–2010 and the Swedish Outpatient Care Register for 2001–2010. ORs for IBS were calculated for relatives of individuals who had been diagnosed with IBS compared with relatives of individuals unaffected by IBS as the reference group. ORs were also determined for IBS cases diagnosed in primary healthcare in four Swedish counties (2001–2007). <h3>Results</h3> The ORs for IBS were 1.75 in siblings (95% CI 1.63 to 1.89), 1.82 in offspring (1.67 to 1.97), 1.90 in parents (1.76 to 2.05), 1.10 in maternal half-siblings (0.88 to 1.39), 1.78 in paternal half-siblings (1.48 to 2.15), 1.27 in nieces/nephews (1.18 to 1.38), 1.11 in cousins (1.04 to 1.18), and 1.51 in spouses (1.24 to 1.84) of probands diagnosed with IBS. The OR for probands diagnosed in primary healthcare was 1.82 in siblings (1.52 to 2.18), and 1.82 in offspring (1.49 to 2.21). <h3>Conclusions</h3> The increased IBS risk among first-degree relatives and also second-degree and third-degree relatives indicates a genetic component of the familial clustering of IBS. However, a non-genetic contribution is also suggested by the increased risk among spouses.
Selective Regulation of ICAM-1 and RANTES Gene Expression after ICAM-1 Ligation on Human Renal Fibroblasts
Authors: Robert Blaber, Eleni Stylianou, Aled Clayton, Robert Steadman
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Leukocyte infiltration of the cortico-interstitium is characteristic of many forms of progressive renal disease. The principal adhesion molecule expressed on resident interstitial cells and recognized by leukocytes is intercellular adhesion molecule–1 (ICAM-1). ICAM-1 is an inducible transmembrane receptor, which forms the counter-receptor for the leukocyte β2 integrins. ICAM-1–dependent binding induces the synthesis of the chemokine RANTES and of ICAM-1 itself. This study examines some of the signaling pathways involved in this induction. After ICAM-1 cross-linking on fibroblasts, the mRNA and protein for both RANTES and ICAM-1 were induced. This induction was calcium-dependent and inhibited by BAPTA-AM. The p38, ERK1, and ERK2 MAP kinases were activated in a [Ca2+]i-dependent manner, with a maximum phosphorylation at approximately 3 min after cross-linking. Through the use of selective inhibitors of p38 MAP kinase (SB203580) or MEKK (PD98059), p38 but not ERK activation was shown to be essential for the induction of ICAM-1. Neither was involved in RANTES activation, however. These mechanisms differed from those initiated by TNF-α, which were not [Ca2+]i-dependent. Electrophoretic mobility shift analysis demonstrated a time-dependent induction of both AP-1 and NF-κB binding activity in nuclear extracts, maximal at approximately 15 min after ICAM-1 cross-linking. Only AP-1 activation, however, was calcium-dependent, suggesting the central involvement of this transcription factor in ICAM-1 and RANTES induction after the ligation of ICAM-1. This study suggests an independent mechanism of inflammatory amplification, which may be characteristic of a persistent leukocytic involvement in areas of chronic inflammation rather than in cytokine-induced acute inflammation. E-mail: [email protected]
Immunisation registers in Canada: progress made, current situation, and challenges for the future
Authors: J A Laroche, A J Diniz
Journal: Eurosurveillance (2012)

Immunisation registers have the capacity to capture data on the administration of vaccine doses at the individual level within the population and represent an important tool in assessing immunisation coverage and vaccine uptake. In 1999, the National Advisory Committee on Immunization recommended that a network of immunisation registers be established in Canada. The Canadian Immunization Registry Network (CIRN) was established to coordinate the development of standards and facilitate the sharing of knowledge and experience to develop a national network of such registers. In 2003, the National Immunization Strategy identified immunisation registers as an important component in improving national immunisation surveillance. In addition, there has been consistent public and professional interest in a national immunisation register being available and considerable progress has been made in developing technologies to facilitate the capture of immunisation-related data. More specifically, the automated identification of vaccines, through the use of barcodes on vaccines, will facilitate collection of data related to administered vaccine doses. Nevertheless, challenges remain in the implementation of immunisation registers in all Canadian provinces and territories such that Canada still does not currently have a fully functional network of immunisation registers with the capacity to be interoperable between jurisdictions and to allow for data to be captured at the national level.
IMMUNOCHEMICAL STUDIES OF ANTITOXIN PRODUCED IN NORMAL AND ALLERGIC INDIVIDUALS HYPERIMMUNIZED WITH DIPHTHERIA TOXOID
Authors: William J. Kuhns
Journal: The Journal of Experimental Medicine (1953)

The Arthus reaction was studied in guinea pigs passively immunized with human diphtheria antitoxin. Diphtheria toxoid was given intradermally 24 hours following the intravenous administration of antitoxin and the subsequent reactions were graded and measured. The intensity of Arthus reactions was dependent upon the relative amounts of precipitating antitoxin and toxoid used. Severe lesions were caused by intravenous sensitization with 0.48 mg. precipitating antitoxin N and intradermal challenge with 0.05 or 0.17 toxoid N. Reactions of lesser intensity were caused by smaller amounts of antitoxin and toxoid. The nature of the antibody used for sensitization was of importance in the severity of Arthus reactions. In contrast to the behavior of precipitating antitoxin, amounts of non-precipitating antitoxin equivalent to 0.48 mg. N did not cause severe Arthus reactions when 0.05 or 0.17 mg. toxoid N was given intradermally. Precipitating antitoxic whole serum is altered by heating at 56 degrees C. for 5 hours so that its precipitability is lost without any appreciable loss of antitoxic strength. This modified antitoxin produced Arthus reactions of only intermediate severity in guinea pigs sensitized with 0.48 mg. antitoxin N. When fractions of precipitating antitoxic serum were obtained using a cold ethanol technique described by Deutsch (16), a mixture of the purified gamma(2)-globulin and the crude albumin fraction heated together at 56 degrees C. for 5 hours behaved similarly to whole serum. However, gamma(2)-globulin alone was not affected by the heating procedure, remained precipitable by toxoid, and was able to cause a severe Arthus reaction following sensitization with 0.48 mg. antitoxin N.
Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propranolol for prevention of variceal rebleeding
Authors: M Rössle, P Deibert, K Haag, A Ochs, M Olchewski, V Siegerstetter, K-H Hauenstein, R Geiger, C Stiepak, W Keller, HE Blum
Journal: The Lancet (1997)