tbuckley/cabot-search huggingface dataset:
Dopamine Inhibits Angiotensin-Stimulated Aldosterone Biosynthesis in Bovine Adrenal Cells
Authors: Terence J. Mc Kenna, Donald P. Island, Wendell E. Nicholson, Grant W. Liddle
Journal: Journal of Clinical Investigation (1979)

The possibility that dopamine may play a role in the in vivo control of aldosterone production in man was suggested to us by reports from others; (a) that bromocriptine, a dopaminergic agonist, inhibits the aldosterone response to diuresis and to the infusion of angiotensin or ACTH; and (b) that metaclopramide, a dopamine blocking agent, causes elevations in plasma aldosterone levels. To determine whether such effects were direct or indirect, we examined the action of dopamine on aldosterone biosynthesis in isolated, bovine adrenal cells. Dopamine significantly inhibits the aldosterone response to angiotensin (P < 0.001), but does not influence basal aldosterone biosynthesis.
Impaired Insulin Secretion After Prenatal Exposure to the Dutch Famine
Authors: Susanne R. de Rooij, Rebecca C. Painter, David I.W. Phillips, Clive Osmond, Robert P.J. Michels, Ian F. Godsland, Patrick M.M. Bossuyt, Otto P. Bleker, Tessa J. Roseboom
Journal: Diabetes Care (2006)

We previously reported that people prenatally exposed to famine during the Dutch Hunger Winter of 1944-1945 have higher 2-h glucose concentrations after an oral glucose tolerance test in later life. We aimed to determine whether this association is mediated through alterations in insulin secretion, insulin sensitivity, or a combination of both.We performed a 15-sample intravenous glucose tolerance test in a subsample of 94 normoglycemic men and women from the Dutch Famine Birth Cohort. We used the disposition index, derived as the product of insulin sensitivity and the first-phase insulin response to glucose as a measure of the activity of the beta-cells adjusted for insulin resistance. In all analyses, we adjusted for sex and BMI.Glucose tolerance was impaired in people who had been prenatally exposed to famine compared with people unexposed to famine (difference in intravenous glucose tolerance test K(g) value -21% [95% CI -41 to -4]). People exposed to famine during midgestation had a significantly lower disposition index (-53% [-126 to -3]) compared with people unexposed to famine. Prenatal exposure to famine during early gestation was also associated with a lower disposition index, but this difference did not reach statistical significance.Impaired glucose tolerance after exposure to famine during mid-gestation and early gestation seems to be mediated through an insulin secretion defect.
Synaptic Modification by Correlated Activity: Hebb's Postulate Revisited
Authors: Guo-qiang Bi, Mu-ming Poo
Journal: Annual Review of Neuroscience (2001)

Correlated spiking of pre- and postsynaptic neurons can result in strengthening or weakening of synapses, depending on the temporal order of spiking. Recent findings indicate that there are narrow and cell type-specific temporal windows for such synaptic modification and that the generally accepted input- (or synapse-) specific rule for modification appears not to be strictly adhered to. Spike timing-dependent modifications, together with selective spread of synaptic changes, provide a set of cellular mechanisms that are likely to be important for the development and functioning of neural networks. When an axon of cell A is near enough to excite cell B or repeatedly or consistently takes part in firing it, some growth or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased.
Protein Synthesis at Synaptic Sites on Dendrites
Authors: Oswald Steward, Erin M. Schuman
Journal: Annual Review of Neuroscience (2001)

▪ Abstract Studies over the past 20 years have revealed that gene expression in neurons is carried out by a distributed network of translational machinery. One component of this network is localized in dendrites, where polyribosomes and associated membranous elements are positioned beneath synapses and translate a particular population of dendritic mRNAs. The localization of translation machinery and mRNAs at synapses endows individual synapses with the capability to independently control synaptic strength through the local synthesis of proteins. The present review discusses recent studies linking synaptic plasticity to dendritic protein synthesis and mRNA trafficking and considers how these processes are regulated. We summarize recent information about how synaptic signaling is coupled to local translation and to the delivery of newly transcribed mRNAs to activated synaptic sites and how local translation may play a role in activity-dependent synaptic modification.
Multifocality and multicentricity in breast cancer and survival outcomes
Authors: S.P. Lynch, X. Lei, M. Chavez-MacGregor, L. Hsu, F. Meric-Bernstam, T.A. Buchholz, A. Zhang, G.N. Hortobagyi, V. Valero, A.M. Gonzalez-Angulo
Journal: Annals of Oncology (2012)
STAT5 is a potent negative regulator of TFH cell differentiation
Authors: Robert J. Johnston, Youn Soo Choi, Jeffrey A. Diamond, Jessica A. Yang, Shane Crotty
Journal: The Journal of Experimental Medicine (2012)

Follicular helper T cells (TFH cells) constitute the CD4+ T cell subset that is specialized to provide help to germinal center (GC) B cells and, consequently, mediate the development of long-lived humoral immunity. TFH cell differentiation is driven by the transcription factor Bcl6, and recent studies have identified cytokine and cell–cell signals that drive Bcl6 expression. However, although TFH dysregulation is associated with several major autoimmune diseases, the mechanisms underlying the negative regulation of TFH cell differentiation are poorly understood. In this study, we show that STAT5 inhibits TFH cell differentiation and function. Constitutive STAT5 signaling in activated CD4+ T cells selectively blocked TFH cell differentiation and GCs, and IL-2 signaling was a primary inducer of this pathway. Conversely, STAT5-deficient CD4+ T cells (mature STAT5fl/fl CD4+ T cells transduced with a Cre-expressing vector) rapidly up-regulated Bcl6 expression and preferentially differentiated into TFH cells during T cell priming in vivo. STAT5 signaling failed to inhibit TFH cell differentiation in the absence of the transcription factor Blimp-1, a direct repressor of Bcl6 expression and TFH cell differentiation. These results demonstrate that IL-2, STAT5, and Blimp-1 collaborate to negatively regulate TFH cell differentiation.
Calcineurin Inhibition in Hypertrophy
Authors: Gerald W. Dorn
Journal: Circulation (2001)

eactive cardiac hypertrophy has long been recognized as a compensatory process that enhances ventricular function through normalization of wall stress in the face of increased hemodynamic load.For almost as long, it has also been appreciated that the natural history of a hypertrophied heart faced with unremitting hemodynamic overload is progression from a state of functional compensation to one of functional decompensation, or heart failure. 1 Under these circumstances, the heart dilates and fails because hypertrophy fails, and in this manner, nature's temporary cure for hemodynamic overload becomes part and parcel of the disease.
Evolution of pathology.
Authors: I Friedmann
Journal: BMJ (1972)

August, p. 329) should have mentioned co-trimoxazole as an alternative drug to chloramphenicol in the treatment of typhoid fever.To date we have successfully treated over 30 patients with acute typhoid or paratyphoid A fever with this drug.'But in addition we have found co-trimoxazole to be very useful in the treatment of chronic salmonellosis where antibiotic treatment usually has to be given for at least four to six weeks.2In patients with irreparably damaged urinary tracts due to schistosomiasis and persistent salmonella urinary excretion prolonged suppressive therapy with co- trimoxazole has successfully maintained the urine s:erile for over a year.4-Weare, etc.,
Lung adenocarcinoma subtypes based on expression of human airway basal cell genes
Authors: Tomoya Fukui, Renat Shaykhiev, Francisco Agosto-Perez, Jason G. Mezey, Robert J. Downey, William D. Travis, Ronald G. Crystal
Journal: European Respiratory Journal (2013)

Lung cancer, including lung adenocarcinoma, is a heterogeneous disease, which evolves from molecular alterations in the airway epithelium. This study explores whether a subtype of lung adenocarcinomas expresses the unique molecular features of human airway basal cells (BCs), and how expression of the airway BC features correlates with the molecular, pathological and clinical phenotype of lung adenocarcinoma. Three independent lung adenocarcinoma data sets were analysed for expression of genes that constitute the airway BC signature. Expression of the BC signature in lung adenocarcinoma was then correlated to clinical and biological parameters. Remarkable enrichment of airway BC signature genes was found in lung adenocarcinomas. A subset of lung adenocarcinomas (BC-high adenocarcinoma) exhibited high expression of BC signature genes in association with poorer tumour grade, higher frequency of vascular invasion and shorter survival than adenocarcinomas with lower expression of these genes. At the molecular level, BC-high adenocarcinomas displayed a higher frequency of <i>KRAS</i> mutations, activation of transcriptional networks and pathways related to cell cycle, extracellular matrix organisation, and a distinct differentiation pattern with suppression of ciliated and exocrine bronchiolar cell (Clara cell)-related genes. Activation of the airway BC programme is a molecular feature of a distinct, aggressive subtype of lung adenocarcinoma.
Characteristics and Outcomes of Children With the Wilms Tumor-Aniridia Syndrome: A Report From the National Wilms Tumor Study Group
Authors: Norman E. Breslow, Robin Norris, Patricia A. Norkool, Tammy Kang, J. Bruce Beckwith, Elizabeth J. Perlman, Michael L. Ritchey, Daniel M. Green, Kim E. Nichols
Journal: Journal of Clinical Oncology (2003)

Purpose: Children with the rare Wilms tumor (WT)-aniridia (WAGR) syndrome have not had systematic evaluation of their clinical and pathologic features. We compared demographics, disease characteristics, and treatment outcomes in a large cohort of WT patients who did or did not have the WAGR syndrome. Patients and Methods: Clinical and pathology records were reviewed for 8,533 patients enrolled between 1969 and 2002 by the National Wilms Tumor Study Group. Results: Sixty-four patients (0.75%) had the WAGR syndrome. For WAGR and non-WAGR patients, respectively, the average birth weights (2.94 and 3.45 kg), median ages at diagnosis (22 and 39 months), and the percentages with bilateral disease (17% and 6%), metastatic disease (2% and 13%), favorable histology (FH) tumors (100% and 92%), and intralobar nephrogenic rests (ILNR; 77% and 22%) all differed. Survival estimates for WAGR and non-WAGR patients were 95% ± 3% and 92% ± 0.3% at 4 years but 48% ± 17% and 86% ± 1.0%, respectively, at 27 years from diagnosis. Five late deaths in WAGR patients were from end-stage renal disease (ESRD). Conclusion: The excess of bilateral disease, ILNR-associated FH tumors of mixed cell type, and early ages at diagnosis in WAGR patients all fit the known phenotypic spectrum of constitutional deletion of chromosome 11p13. Despite a favorable response of their WT to treatment, WAGR patients have a high risk of ESRD as they approach adulthood. The renal pathology associated with this apparent late manifestation of WT1 deletion, and the explanation for the abnormally low birth weights in patients with del 11p13, have yet to be determined.
Transplantation of Bone Marrow–Derived Mononuclear Cells in Ischemic Apolipoprotein E–Knockout Mice Accelerates Atherosclerosis Without Altering Plaque Composition
Authors: Jean-Sébastien Silvestre, Andrea Gojova, Valérie Brun, Stéphane Potteaux, Bruno Esposito, Micheline Duriez, Michel Clergue, Sophie Le Ricousse-Roussanne, Véronique Barateau, Régine Merval, Hervé Groux, Gérard Tobelem, Bernard Levy, Alain Tedgui, Ziad Mallat
Journal: Circulation (2003)

Bone marrow-derived mononuclear cells (BM-MNCs) enhance postischemic neovascularization, and their therapeutic use is currently under clinical investigation. We evaluated the safety of BM-MNC-based therapy in the setting of atherosclerosis.Apolipoprotein E (apoE)-knockout (KO) mice were divided into 4 groups: 20 nonischemic mice receiving intravenous injection of either saline (n=10) or 10(6) BM-MNCs from wild-type animals (n=10) and 20 mice with arterial femoral ligature receiving intravenous injection of either saline (n=10) or 10(6) BM-MNCs from wild-type animals (n=10) at the time of ischemia induction. Animals were monitored for 4 additional weeks. Atherosclerosis was evaluated in the aortic sinus. BM-MNC transplantation improved tissue neovascularization in ischemic hind limbs, as revealed by the 210% increase in angiography score (P<0.0001), the 33% increase in capillary density (P=0.01), and the 65% increase in tissue Doppler perfusion score (P=0.0002). Hindlimb ischemia without BM-MNC transplantation or BM-MNC transplantation without ischemia did not affect atherosclerotic plaque size. However, transplantation of 10(6) BM-MNCs into apoE-KO mice with hindlimb ischemia induced a significant 48% to 72% increase in lesion size compared with the other 3 groups (P=0.0025), despite similar total cholesterol levels. Transplantation of 10(5) BM-MNCs produced similar results, whereas transplantation of 10(6) apoE-KO-derived BM-MNCs had neither proangiogenic nor proatherogenic effects. There was no difference in plaque composition between groups.BM-MNC therapy is unlikely to affect atherosclerotic plaque stability in the short term. However, it may promote further atherosclerotic plaque progression in an ischemic setting.
Essential Role of Aldehyde Dehydrogenase 1A3 for the Maintenance of Non–Small Cell Lung Cancer Stem Cells Is Associated with the STAT3 Pathway
Authors: Chunli Shao, James P. Sullivan, Luc Girard, Alexander Augustyn, Paul Yenerall, Jaime Rodriguez-Canales, Hui Liu, Carmen Behrens, Jerry W. Shay, Ignacio I. Wistuba, John D. Minna
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Lung cancer stem cells (CSC) with elevated aldehyde dehydrogenase (ALDH) activity are self-renewing, clonogenic, and tumorigenic. The purpose of our study is to elucidate the mechanisms by which lung CSCs are regulated. Experimental Design: A genome-wide gene expression analysis was performed to identify genes differentially expressed in the ALDH+ versus ALDH− cells. RT-PCR, Western blot analysis, and Aldefluor assay were used to validate identified genes. To explore the function in CSCs, we manipulated their expression followed by colony and tumor formation assays. Results: We identified a subset of genes that were differentially expressed in common in ALDH+ cells, among which ALDH1A3 was the most upregulated gene in ALDH+ versus ALDH− cells. shRNA-mediated knockdown of ALDH1A3 in non–small cell lung cancer (NSCLC) resulted in a dramatic reduction in ALDH activity, clonogenicity, and tumorigenicity, indicating that ALDH1A3 is required for tumorigenic properties. In contrast, overexpression of ALDH1A3 by itself it was not sufficient to increase tumorigenicity. The ALDH+ cells also expressed more activated STAT3 than ALDH− cells. Inhibition of STAT3 or its activator EZH2 genetically or pharmacologically diminished the level of ALDH+ cells and clonogenicity. Unexpectedly, ALDH1A3 was highly expressed in female, never smokers, well-differentiated tumors, or adenocarcinoma. ALDH1A3 low expression was associated with poor overall survival. Conclusions: Our data show that ALDH1A3 is the predominant ALDH isozyme responsible for ALDH activity and tumorigenicity in most NSCLCs, and that inhibiting either ALDH1A3 or the STAT3 pathway are potential therapeutic strategies to eliminate the ALDH+ subpopulation in NSCLCs. Clin Cancer Res; 20(15); 4154–66. ©2014 AACR.
Health-related quality of life in patients with high-grade glioma
Authors: Jin-xiang Cheng, Xiang Zhang, Bo-Lin Liu
Journal: Neuro-Oncology (2008)

Health-related quality of life (HRQOL) has become an increasingly important endpoint in cancer studies; however, the research into the HRQOL of patients with high-grade glioma (HGG) is sparse compared with that for patients with other neoplasms. Owing to the specific location and poor prognosis, it is more important and difficult to study HRQOL in patients with HGG than in those with other tumors; furthermore, the study of HRQOL in patients with HGG differs from that for patients with other tumors. In this review, we identified and compared the most frequently used instruments to assess HRQOL; analyzed specific facets and determinants of HRQOL (such as sex, tumor location and histological classification, depression, and cognitive function), as well as the association between HRQOL and survival; and appraised the effects of new treatments on HRQOL in patients with HGG from randomized controlled trials. Furthermore, we detected broadly existing problems and many contradictory outcomes and gave some proper interpretation and suggestions regarding them.
Universal Cancer Peptide-Based Therapeutic Vaccine Breaks Tolerance against Telomerase and Eradicates Established Tumor
Authors: Magalie Dosset, Yann Godet, Charline Vauchy, Laurent Beziaud, Yu Chun Lone, Christine Sedlik, Christelle Liard, Emeline Levionnois, Bertrand Clerc, Federico Sandoval, Etienne Daguindau, Simon Wain-Hobson, Eric Tartour, Pierre Langlade-Demoyen, Christophe Borg, Olivier Adotévi
Journal: Clinical Cancer Research (2012)

To evaluate CD4(+) helper functions and antitumor effect of promiscuous universal cancer peptides (UCP) derived from telomerase reverse transcriptase (TERT).To evaluate the widespread immunogenicity of UCPs in humans, spontaneous T-cell responses against UCPs were measured in various types of cancers using T-cell proliferation and ELISPOT assays. The humanized HLA-DRB1*0101/HLA-A*0201 transgenic mice were used to study the CD4(+) helper effects of UCPs on antitumor CTL responses. UCP-based antitumor therapeutic vaccine was evaluated using HLA-A*0201-positive B16 melanoma that express TERT.The presence of a high number of UCP-specific CD4(+) T cells was found in the blood of patients with various types of cancer. These UCP-specific T cells mainly produce IFN-γ and TNF-α. In HLA transgenic mice, UCP vaccinations induced high avidity CD4(+) T(H)1 cells and activated dendritic cells that produced interleukin-12. UCP-based vaccination breaks self-tolerance against TERT and enhances primary and memory CTL responses. Furthermore, the use of UCP strongly improves the efficacy of therapeutic vaccination against established B16-HLA-A*0201 melanoma and promotes tumor infiltration by TERT-specific CD8(+) T cells.Our results showed that UCP-based vaccinations strongly stimulate antitumor immune responses and could be used to design efficient immunotherapies in multiple types of cancers.
CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation.
Authors: K Kato, M Koyanagi, H Okada, T Takanashi, Y W Wong, A F Williams, K Okumura, H Yagita
Journal: The Journal of Experimental Medicine (1992)

CD2 is an intercellular adhesion molecule that has been implicated in T cell activation and differentiation both in humans and mice. Although the ligand for human CD2 has been defined as LFA-3, that for murine CD2 has not been identified yet. To identify the ligand for mouse CD2, we generated a chimeric molecule consisting of the extracellular domain of mouse CD2 and human immunoglobulin (Ig)G1 Fc (mCD2Rg). A hamster monoclonal antibody (mAb), HM48-1, was established by screening mAbs that could block the binding of mCD2Rg to T cell lines at the ligand site. The putative mouse CD2 ligand recognized by this mAb was a glycosyl phosphatidylinositol-anchored glycoprotein with an apparent molecular mass of 45 kD, which were shared characteristics with human LFA-3. However, its expression was predominantly restricted to hematopoietic cells, unlike human LFA-3. Protein microsequencing analysis for the NH2-terminal 18 amino acid residues of the affinity-purified HM48-1 antigen revealed that it is almost identical with mouse CD48. This identity was further confirmed by the reactivity of HM48-1 with a soluble recombinant CD48 (sCD48) protein and the molecule recognized by a rat mAb raised against sCD48. A rat anti-CD48 mAb blocked the mCD2Rg binding as well as HM48-1. Moreover, sCD48 also inhibited the mCD2Rg binding to the cellular ligand. Finally, like anti-CD2 mAb, HM48-1 inhibited the phytohemagglutinin response and, when crosslinked, augmented the anti-CD3 response of splenic T cells. These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation.
Intracellular calcium transients in myocardium from spontaneously hypertensive rats during the transition to heart failure.
Authors: O H Bing, W W Brooks, C H Conrad, S Sen, C L Perreault, J P Morgan
Journal: Circulation Research (1991)

To investigate the mechanism of impaired myocardial function after long-term pressure overload, we studied cardiac muscle mechanical contraction and intracellular calcium transients using the bioluminescent indicator aequorin. Left ventricular papillary muscle preparations were examined from three groups of rats: 1) aging spontaneously hypertensive rats (SHR) with clinical and pathological evidence suggesting heart failure (SHR-F group), 2) age-matched SHRs with no evidence of heart failure (SHR-NF group), and 3) age-matched normotensive Wistar-Kyoto rats (WKY group). Isometric force development was depressed in both SHR groups relative to the WKY group. Resting [Ca2+]i was lower in the SHR-F group, and the time to peak [Ca2+]i was prolonged in this group. The relative increases in peak [Ca2+]i with the inotropic interventions of increased [Ca2+]o and the addition of isoproterenol were similar among groups. Although inotropy increased in all groups with increased [Ca2+]o, after isoproterenol, inotropy increased only in the WKY group. Thus, in SHR myocardium, [Ca2+]i increased after isoproterenol, but inotropy failed to increase. Myosin isozymes were shifted toward the V3 isoform in both SHR groups; the V3 isoform was virtually 100% in papillary muscles from the SHR-F group. These changes may reflect events directly contributing to the development of heart failure or represent adaptive changes to chronic pressure overload and heart failure.
Getting Scotland on the move? Reflections on a 5-year review of Scotland's national physical activity strategy
Authors: Emma Halliday, Nanette Mutrie, Fiona Bull
Journal: British Journal of Sports Medicine (2013)

The public health risks of physical inactivity have led many national governments to develop policies that aim to increase population levels of physical activity. There is however, little evidence available about the effectiveness of such strategies and physical activity leaders may also face challenges in securing sufficient levels of political will and lasting investment for physical activity. This article reports on a review of a national physical activity strategy in Scotland after 5 years of implementation and offers lessons that may assist policymakers, practitioners and communities seeking to mobilise political commitment and leadership for physical activity in their own countries.