tbuckley/cabot-search huggingface dataset:
Diffuse intrinsic pontine gliomas: New waves
Authors: R. Nishikawa
Journal: Neuro-Oncology (2012)

Brainstem lesions are heterogenous. Although the majority are astrocytomas, adult and pediatric gliomas differ in their molecular genetic aberrations; gliomas located in the brainstem differ biologically from those located supratentorially; and there is tremendous intratumoral variation in histologic type and genetic profile, as shown in the paper by Warren et al (1) in this issue of Neuro-Oncology. We must perform biopsies to determine the precise histologic types and genetic profiles of lesions in the brainstem. However, textbooks usually state that biopsy or surgery is not required for the diagnosis or treatment of diffuse intrinsic pontine gliomas (DIPGs) and cannot be recommended routinely; diagnosis can be made using MRI alone. The advent of stereotactic biopsy has made the surgical diagnosis of brainstem lesions less dangerous and more feasible. In this issue of the journal, Dellaretti et al (2) report on 96 brainstem biopsies performed at the Roger Salengro Hospital in Lille, France, between February 1988 and August 2007. The overall morbidity rate associated with biopsy was 9%, and one patient died of causes associated with the procedure; these morbidity and mortality rates are considered acceptable. Stereotactic biopsy makes it possible to conduct new clinical studies of DIPG, such as a currently ongoing phase II trial to determine survival after molecularly determined treatment in children and young adults with newly diagnosed DIPG (http://clinicaltrials.gov/ ct2/show/NCT01182350). MRI-guided stereotactic biopsies will be performed. On the basis of molecular parameters after biopsy, patients will receive erlotinib or temozolomide after radiotherapy with bevacizumab. Stratification will be based on O 6 -methylguanine-DNA methyltransferase promoter methylation status and epidermal growth factor receptor expression in tumor biopsy samples. These new treatments for DIPG are now raising hopes for responses to tailored treatment.
Rare genetic variation at Zea mays crtRB1 increases β-carotene in maize grain
Authors: Jianbing Yan, Catherine Bermudez Kandianis, Carlos E Harjes, Ling Bai, Eun-Ha Kim, Xiaohong Yang, Debra J Skinner, Zhiyuan Fu, Sharon Mitchell, Qing Li, Maria G Salas Fernandez, Maria Zaharieva, Raman Babu, Yang Fu, Natalia Palacios, Jiansheng Li, Dean DellaPenna, Thomas Brutnell, Edward S Buckler, Marilyn L Warburton, Torbert Rocheford
Journal: Nature Genetics (2010)
Detachment of Corneal Epithelium(?)
Authors: J. A. Menzies
Journal: BMJ (1900)

LzeIDIAuJoURP 623Largin is also of service after trachoma operations, as, for oxample, squeezing or "brushing " the conjunctiva, where, in my experience, it is equal to silver nitrate.Largin will sometimes bring about a speedy cure in that form of chronic opthalmia associated with the diplo-bacillus of Morax.But, as a rule, it is markedly inferior to a watery solution of zinc sulphate, Io to 40 grs. to the ounce.CASE v.-A.F., aged 7 years, suffered from slight congestion of the pal- pebral conjunctiva, soreness at the angles of the licis, and a mucous secretion from the eyes.Enormous masses of diplobacilli were present in cover-glass preparations from the secretion, and the organisms were cultivated on blood serum and blood agar.After eight daily applications of 5 per cent.largin, the condition of the conjunctiva was good and diplo- bacilli could not be demonstrated.CASE vI.-In the case of E. G., aged 8 years, the characteristic micro- parasites did not disappear until twelve applications had been made of IO per cent.largin.
Management of Bipolar Disorder During Pregnancy and the Postpartum Period
Authors: Kimberly A. Yonkers, Katherine L. Wisner, Zachary Stowe, Ellen Leibenluft, Lee Cohen, Laura Miller, Rachel Manber, Adele Viguera, Trisha Suppes, Lori Altshuler
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Bipolar disorder affects 0.5%–1.5% of individuals in the United States. The typical age at onset is late adolescence or early adulthood, placing women at risk for episodes throughout their reproductive years. General guidelines for the treatment of bipolar disorder are available from the American Psychiatric Association, but additional issues arise when these guidelines are applied in the treatment of peripartum women. The authors summarize knowledge regarding the management of bipolar disorder during pregnancy and the postpartum period, with a focus on managing mania, hypomania, and the psychotic components of the illness. METHOD: An expert panel reviewed articles that address the management of bipolar disorder and the consequences of the use of mood stabilizers during pregnancy, and a consensus document was generated. RESULTS: The treatment of bipolar disorder in pregnant women involves significant challenges. Some mood stabilizers, e.g., sodium valproate and carbamazepine, are human teratogens. On the other hand, the teratogenicity associated with lithium may have been overestimated in the past. CONCLUSIONS: Since treatment can be managed most effectively if pregnancy is planned, clinicians should discuss the issue of pregnancy and its management with every bipolar disorder patient who has childbearing potential, regardless of future reproductive plans. Additional research should address the risks of disturbed sleep to pregnant and postpartum women with bipolar disorder, as well as structural and behavioral consequences to offspring when mood stabilizers are used during pregnancy. Longitudinal and cohort studies can promote these efforts. Given the rate of bipolar disorder in the general population, research efforts will need to be broad based and include multiple collaborating centers.
Post-irradiation morphoea
Authors: J. Verbov
Journal: British Journal of Dermatology (1989)

Journal Article Post‐irradiation morphoea Get access J. Verbov J. Verbov Department of Dermatology, Roy al Liverpool Hospital, Prescot Street, Liverpool, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 121, Issue 6, 1 December 1989, Pages 819–820, https://doi.org/10.1111/j.1365-2133.1989.tb08227.x Published: 01 December 1989
Vinorelbine and prednisone in frail elderly patients with intermediate-high grade non-Hodgkin's lymphomas
Authors: S. Monfardini, S.M.L. Aversa, V. Zoli, L. Salvagno, A. Bianco, R. Bordonaro, G. Benevolo, M. Crugnola, G. Crivellari, P. Vivaldi, U. Basso, V. Torri
Journal: Annals of Oncology (2005)
A negative feedback loop mediated by the Bcl6–cullin 3 complex limits Tfh cell differentiation
Authors: Rebecca Mathew, Ai-ping Mao, Andrew H. Chiang, Clara Bertozzi-Villa, Jeffrey J. Bunker, Seth T. Scanlon, Benjamin D. McDonald, Michael G. Constantinides, Kristin Hollister, Jeffrey D. Singer, Alexander L. Dent, Aaron R. Dinner, Albert Bendelac
Journal: The Journal of Experimental Medicine (2014)

Induction of Bcl6 (B cell lymphoma 6) is essential for T follicular helper (Tfh) cell differentiation of antigen-stimulated CD4+ T cells. Intriguingly, we found that Bcl6 was also highly and transiently expressed during the CD4+CD8+ (double positive [DP]) stage of T cell development, in association with the E3 ligase cullin 3 (Cul3), a novel binding partner of Bcl6 which ubiquitinates histone proteins. DP stage–specific deletion of the E3 ligase Cul3, or of Bcl6, induced the derepression of the Bcl6 target genes Batf (basic leucine zipper transcription factor, ATF-like) and Bcl6, in part through epigenetic modifications of CD4+ single-positive thymocytes. Although they maintained an apparently normal phenotype after emigration, they expressed increased amounts of Batf and Bcl6 at basal state and produced explosive and prolonged Tfh responses upon subsequent antigen encounter. Ablation of Cul3 in mature CD4+ splenocytes also resulted in dramatically exaggerated Tfh responses. Thus, although previous studies have emphasized the essential role of Bcl6 in inducing Tfh responses, our findings reveal that Bcl6–Cul3 complexes also provide essential negative feedback regulation during both thymocyte development and T cell activation to restrain excessive Tfh responses.
The Elephant and the Whale
Authors: J. E. Powell
Journal: BMJ (1961)

<h3>Background:</h3> The ESR1 AGATA haplotype is composed of five markers located within introns 5 and 6 of the human oestrogen receptor 1 (<i>ESR1</i>) gene. This haplotype has been studied in several male urogenital tract anomalies and male infertility. In one of these studies, a deviation from Hardy–Weinberg equilibrium (DHW) was found for the ESR1 AGATA marker rs3020375 in two groups of healthy controls. In the present study, we investigated whether the observed DHW is caused by structural variants present within the <i>ESR1</i> gene. <h3>Participants:</h3> 229 family units achieving pregnancy through assisted reproductive technologies (n = 129) or by natural means (n = 100), 2465 general Spanish population controls and 162 men with idiopathic infertility. <h3>Main outcome measurements:</h3> Segregation analyses of genetic markers in family units and case–control genetic association studies. <h3>Results:</h3> We identified a new interstitial deletion of 2244 base pairs within intron 6 of the human <i>ESR1</i> gene as the cause for the observed DHW. This new variant presents a 10% allelic frequency in the general Spanish population and it is associated with idiopathic male infertility (OR = 1.51; p = 0.03). The percentage of infertile couples in which both members carried the <i>ESR1</i> deletion (10.08%) was also a higher than expected value of 6% (p = 0.03). <h3>Conclusions:</h3> We have characterised a novel structural variation in human <i>ESR1</i> gene. The available data indicate a deleterious action of the ESR1 deletion in both male and couple fertility. The potential effects of this deletion on other oestrogen-related diseases need to be determined.
Disruption of Laminin-Integrin-CD151-Focal Adhesion Kinase Axis Sensitizes Breast Cancer Cells to ErbB2 Antagonists
Authors: Xiuwei H. Yang, Ludmila M. Flores, Qinglin Li, Pengcheng Zhou, Fenghui Xu, Ian E. Krop, Martin E. Hemler
Journal: Cancer Research (2010)

Resistance to anti-ErbB2 agents is a significant problem in the treatment of human ErbB2+ breast cancers. We show here that adhesion of human ErbB2+ breast cancer cells to basement membrane laminin-5 provides substantial resistance to trastuzumab and lapatinib, agents that respectively target the extracellular and kinase domains of ErbB2. Knockdown of laminin-binding integrins (alpha6beta4, alpha3beta1) or associated tetraspanin protein CD151 reversed laminin-5 resistance and sensitized ErbB2+ cells to trastuzumab and lapatinib. CD151 knockdown, together with trastuzumab treatment, inhibited ErbB2 activation and downstream signaling through Akt, Erk1/2, and focal adhesion kinase (FAK). Hence, ErbB2 function in mammary tumor cells is promoted by integrin-mediated adhesion to laminin-5, with strong support by CD151, leading to signaling through FAK. Consequently, removal or inhibition of any of these components (laminin-5, integrin, CD151, FAK) markedly sensitizes cells to anti-ErbB2 agents. These new insights should be useful when devising strategies for overcoming drug resistance in ErbB2+ cancers.
A memorable patient: The headache and the rabbi
Authors: P. Arnold
Journal: BMJ (2002)

“The sudden onset of severe headache, in someone who doesn't usually get headaches, especially a young person….”—the professor's words, as best as I recall.

A woman in her mid-30s accompanied her mother to my surgery one afternoon. The appointment was for the mother, who asked if, instead, I could attend to the daughter, who had a severe headache and didn't normally get headaches.

She said that the headache had started suddenly that morning. Asked what she was doing at the time, she said that she was at the children's school's speech day. Which school? “You know, the one on the hill.” …
Prostaglandin D2 relaxes bovine coronary arteries by endothelium-dependent nitric oxide-mediated cGMP formation.
Authors: M Braun, K Schrör
Journal: Circulation Research (1992)

This study investigates the vasomotor activities of prostaglandin (PG) D2 in bovine coronary arteries in relation to endothelial function. Isolated segments of bovine coronary arteries with intact endothelium were concentration-dependently relaxed by PGD2 (0.01-1 microM), a reaction that was blocked by a selective PGD receptor antagonist (BW A868C). There was a tight correlation between PGD2- and acetylcholine-induced relaxations (r = 0.894, n = 96, p &lt; 0.001). Removal of endothelium abolished the PGD2-induced relaxation and unmasked a contractile activity of the compound. Inhibition of endogenous PGI2 formation by indomethacin did not modify these responses, whereas inhibition of endogenous nitric oxide generation by NG-nitro-L-arginine and NG-monomethyl L-arginine (10 or 100 microM) or scavenging of released nitric oxide by oxyhemoglobin (3 microM) considerably (&gt; 50%) antagonized the PGD2-induced relaxation. The vessel relaxation by PGD2 was associated with a threefold to fourfold increase in vascular cGMP. A considerable reduction in vascular cGMP was measured after removal of the endothelium (by 53%) and inhibition of endogenous nitric oxide generation by NG-nitro-L-arginine (by 70%). This also resulted in a complete inhibition of PGD2-induced cGMP accumulation. Similar results were obtained with the stable PGD2 mimetic ZK 110.841, suggesting that these biological activities of PGD2 were due to the compound itself and not caused by any PGD2 metabolite. A slight but significant increase in cAMP was observed in arteries with intact endothelium as well as after removal of endothelium. Because the relaxing effect of PGD2 was strictly endothelium dependent, the observed relaxation cannot be explained by cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Does PTEN Loss Impair DNA Double-Strand Break Repair by Homologous Recombination?
Authors: Clayton R. Hunt, Arun Gupta, Nobuo Horikoshi, Tej K. Pandita
Journal: Clinical Cancer Research (2011)

Abstract The tumor suppressor PTEN is frequently lost in cancer cells, resulting in altered radiation and drug sensitivity. However, the role of PTEN in DNA repair is controversial. Detailed studies in prostate cancer cells now indicate PTEN does not regulate RAD51 expression or homologous recombination and is not a biomarker for PARP inhibitor sensitivity. Clin Cancer Res; 18(4); 920–2. ©2011 AACR.
DLL4-Notch Signaling Mediates Tumor Resistance to Anti-VEGF Therapy <i>In Vivo</i>
Authors: Ji-Liang Li, Richard C.A. Sainson, Chern Ein Oon, Helen Turley, Russell Leek, Helen Sheldon, Esther Bridges, Wen Shi, Cameron Snell, Emma T. Bowden, Herren Wu, Partha S. Chowdhury, Angela J. Russell, Craig P. Montgomery, Richard Poulsom, Adrian L. Harris
Journal: Cancer Research (2011)

Resistance to VEGF inhibitors is emerging as a major clinical problem. Notch signaling has been implicated in tumor angiogenesis. Therefore, to investigate mechanisms of resistance to angiogenesis inhibitors, we transduced human glioblastoma cells with retroviruses encoding Notch delta-like ligand 4 (DLL4), grew them as tumor xenografts and then treated the murine hosts with the VEGF-A inhibitor bevacizumab. We found that DLL4-mediated tumor resistance to bevacizumab in vivo. The large vessels induced by DLL4-Notch signaling increased tumor blood supply and were insensitive to bevacizumab. However, blockade of Notch signaling by dibenzazepine, a γ-secretase inhibitor, disrupted the large vessels and abolished the tumor resistance. Multiple molecular mechanisms of resistance were shown, including decreased levels of hypoxia-induced VEGF and increased levels of the VEGF receptor VEGFR1 in the tumor stroma, decreased levels of VEGFR2 in large blood vessels, and reduced levels of VEGFR3 overall. DLL4-expressing tumors were also resistant to a VEGFR targeting multikinase inhibitor. We also observed activation of other pathways of tumor resistance driven by DLL4-Notch signaling, including the FGF2-FGFR and EphB4-EprinB2 pathways, the inhibition of which reversed tumor resistance partially. Taken together, our findings show the importance of classifying mechanisms involved in angiogenesis in tumors, and how combination therapy to block DLL4-Notch signaling may enhance the efficacy of VEGF inhibitors, particularly in DLL4-upregulated tumors, and thus provide a rational base for the development of novel strategies to overcome antiangiogenic resistance in the clinic.
Incorporation of paramagnetic, fluorescent and PET/SPECT contrast agents into liposomes for multimodal imaging
Authors: Nick Mitchell, Tammy L. Kalber, Margaret S. Cooper, Kavitha Sunassee, Samantha L. Chalker, Karen P. Shaw, Katherine L. Ordidge, Adam Badar, Samuel M. Janes, Philip J. Blower, Mark F. Lythgoe, Helen C. Hailes, Alethea B. Tabor
Journal: Biomaterials (2012)

A series of metal-chelating lipid conjugates has been designed and synthesized. Each member of the series bears a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) macrocycle attached to the lipid head group, using short n-ethylene glycol (n-EG) spacers of varying length. Liposomes incorporating these lipids, chelated to Gd3+, 64Cu2+, or 111In3+, and also incorporating fluorescent lipids, have been prepared, and their application in optical, magnetic resonance (MR) and single-photon emission tomography (SPECT) imaging of cellular uptake and distribution investigated in vitro and in vivo. We have shown that these multimodal liposomes can be used as functional MR contrast agents as well as radionuclide tracers for SPECT, and that they can be optimized for each application. When shielded liposomes were formulated incorporating 50% of a lipid with a short n-EG spacer, to give nanoparticles with a shallow but even coverage of n-EG, they showed good cellular internalization in a range of tumour cells, compared to the limited cellular uptake of conventional shielded liposomes formulated with 7% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethyleneglycol)2000] (DSPE-PEG2000). Moreover, by matching the depth of n-EG coverage to the length of the n-EG spacers of the DOTA lipids, we have shown that similar distributions and blood half lives to DSPE-PEG2000-stabilized liposomes can be achieved. The ability to tune the imaging properties and distribution of these liposomes allows for the future development of a flexible tri-modal imaging agent.
Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy
Authors: Massimiliano Gnecchi, Zhiping Zhang, Aiguo Ni, Victor J. Dzau
Journal: Circulation Research (2008)

Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been initially proposed as mechanisms of stem cell action. However, in many cases, the frequency of stem cell engraftment and the number of newly generated cardiomyocytes and vascular cells, either by transdifferentiation or cell fusion, appear too low to explain the significant cardiac improvement described. Accordingly, we and others have advanced an alternative hypothesis: the transplanted stem cells release soluble factors that, acting in a paracrine fashion, contribute to cardiac repair and regeneration. Indeed, cytokines and growth factors can induce cytoprotection and neovascularization. It has also been postulated that paracrine factors may mediate endogenous regeneration via activation of resident cardiac stem cells. Furthermore, cardiac remodeling, contractility, and metabolism may also be influenced in a paracrine fashion. This article reviews the potential paracrine mechanisms involved in adult stem cell signaling and therapy.
Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes
Authors: Qibin Zhang, Thomas L. Fillmore, Athena A. Schepmoes, Therese R.W. Clauss, Marina A. Gritsenko, Patricia W. Mueller, Marian Rewers, Mark A. Atkinson, Richard D. Smith, Thomas O. Metz
Journal: The Journal of Experimental Medicine (2012)

Using global liquid chromatography-mass spectrometry (LC-MS)–based proteomics analyses, we identified 24 serum proteins that were significantly variant between those with type 1 diabetes (T1D) and healthy controls. Functionally, these proteins represent innate immune responses, the activation cascade of complement, inflammatory responses, and blood coagulation. Targeted verification analyses were performed on 52 surrogate peptides representing these proteins, with serum samples from an antibody standardization program cohort of 100 healthy control and 50 type 1 diabetic subjects. 16 peptides were verified as having very good discriminating power, with areas under the receiver operating characteristic curve ≥0.8. Further validation with blinded serum samples from an independent cohort (10 healthy control and 10 type 1 diabetics) demonstrated that peptides from platelet basic protein and C1 inhibitor achieved both 100% sensitivity and 100% specificity for classification of samples. The disease specificity of these proteins was assessed using sera from 50 age-matched type 2 diabetic individuals, and a subset of proteins, C1 inhibitor in particular, were exceptionally good discriminators between these two forms of diabetes. The panel of biomarkers distinguishing those with T1D from healthy controls and those with type 2 diabetes suggests that dysregulated innate immune responses may be associated with the development of this disorder.
Report of the Pediatric Heart Network and National Heart, Lung, and Blood Institute Working Group on the Perioperative Management of Congenital Heart Disease
Authors: Jonathan R. Kaltman, Dean B. Andropoulos, Paul A. Checchia, J. William Gaynor, Timothy M. Hoffman, Peter C. Laussen, Richard G. Ohye, Gail D. Pearson, Frank Pigula, James Tweddell, Gil Wernovsky, Pedro del Nido
Journal: Circulation (2010)