tbuckley/cabot-search huggingface dataset:
Junctional communication of pancreatic β cells contributes to the control of insulin secretion and glucose tolerance
Authors: Anne Charollais, Asllan Gjinovci, Joachim Huarte, Juliette Bauquis, Angel Nadal, Franz Martín, Etelvina Andreu, Juan V. Sánchez-Andrés, Alessandra Calabrese, Domenico Bosco, Bernat Soria, Claes B. Wollheim, Pedro L. Herrera, Paolo Meda
Journal: Journal of Clinical Investigation (2000)

Proper insulin secretion requires the coordinated functioning of the numerous beta cells that form pancreatic islets. This coordination depends on a network of communication mechanisms whereby beta cells interact with extracellular signals and adjacent cells via connexin channels. To assess whether connexin-dependent communication plays a role in vivo, we have developed transgenic mice in which connexin 32 (Cx32), one of the vertebrate connexins found in the pancreas, is expressed in beta cells. We show that the altered beta-cell coupling that results from this expression causes reduced insulin secretion in response to physiologically relevant concentrations of glucose and abnormal tolerance to the sugar. These alterations were observed in spite of normal numbers of islets, increased insulin content, and preserved secretory response to glucose by individual beta cells. Moreover, glucose-stimulated islets showed improved electrical synchronization of these cells and increased cytosolic levels of Ca(2+). The results show that connexins contribute to the control of beta cells in vivo and that their excess is detrimental for insulin secretion.
Induction of systemic anti-melanoma immunity through intratumoral TLR-7/8 activation
Authors: Manisha Singh, Hiep Khong, Zhimin Dai, John P Vasilakos, Patrick Hwu, Willem W Overwijk
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Intratumoral immune activation can induce systemic immunity and anti-tumor activity. Imiquimod is a cream-formulated, TLR-7 agonist that is FDA-approved for the treatment of non-melanoma skin cancers, but has limited activity against melanoma. In the current study, we studied the
402 Clinical and demographic features of hepatitis C-infected Alaska natives with persistently normal, persistantly elevated or fluxuating alanine transaminase levels
Authors: M BRUCE, D BRUDEN, B MCMAHON, C CHRISTENSEN, C HOMAN, D SULLIVAN, H DUBNER, T HENNESSY, J WILLIAMS, D GRETCH
Journal: Hepatology (2003)

The aim of the present study was to identify a high affinity InsP4 receptor in membranes from cerebellum or brain from several species. In samples obtained from sheep, beef, human and rat, a 42 kDa protein represents an Ins(1,3,4,5)P4 receptor, similar to the InsP4 receptor from pig cerebellum, which we have described previously using an InsP4-photoaffinity analogue (Reiser et al., Biochem. J. 1991, 280, 533). CNBr cleavage of the pig receptor protein for peptide sequencing revealed peptide sequences which demonstrate that the 42 kDa InsP4 receptor is a novel protein. Two synthetic peptides derived from the pig receptor were used to generate peptide-specific antisera which recognized also the intact receptor protein from pig. The two antisera showed different reactivity with the InsP4 receptor purified from pig and human compared to sheep, beef and rat. This indicates a species heterogeneity of this protein.
Abstract 3789: The alternatively spliced PRMT1 isoform PRMT1v2 promotes breast cancer cell survival and invasiveness.
Authors: Robert Mitchell Baldwin, Alan Morettin, Genevieve Paris, Isabelle Goulet, Jocelyn Cote
Journal: Cancer Research (2013)

Abstract Breast cancer is the leading cause of cancer-related deaths in women. Despite intensive treatment to overcome this disease, recurrence is common and often incurable due to the highly aggressive nature of the recurrent tumour. Protein arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs) and plays an important role in many cellular processes. Aberrant PRMT expression has been observed in several common cancer types, however their precise contribution to the cell transformation process and cancer progression is not well understood. Previously, we reported that the PRMT1 gene generates several alternatively spliced isoforms and our initial biochemical characterization of these isoforms revealed that they exhibit distinct substrate specificity and sub-cellular localization. Here we have focused on the PRMT1v2 isoform, which is the only predominantly cytoplasmic isoform and has increased relative expression in breast cancer cell lines and tumours. Specific depletion of PRMT1v2 using RNA interference caused a significant decrease in breast cancer cell survival due to an induction of apoptosis. Furthermore, depletion of PRMT1v2 in MDA-MB-231, an aggressive breast cancer cell line, resulted in significantly decreased cell invasion. Alternatively, PRMT1v2 overexpression in a non-aggressive breast cancer cell line, MCF7, was sufficient to enhance their invasiveness. This novel activity is specific to PRMT1v2, as overexpression of other isoforms did not enhance invasion. It also requires both proper subcellular localization and methylase activity. Consistent with an invasive phenotype, PRMT1v2 overexpression caused altered cell morphology and reduced cell-cell adhesion. Finally, we observed a significant reduction in β-catenin protein levels, a critical cell-cell adhesion protein, and show that this reduction is pivotal to PRMT1v2-enhanced cell invasion. Our study underscores the importance of characterizing the distinct functional differences between PRMT1 isoforms. Overall, we demonstrate a specific role for PRMT1v2 in promoting breast cancer cell survival and invasion, and propose that it may represent a promising therapeutic target. *RMB is a Postdoctoral Fellow of the Canadian Institute of Health Research Citation Format: Robert Mitchell Baldwin, Alan Morettin, Genevieve Paris, Isabelle Goulet, Jocelyn Cote. The alternatively spliced PRMT1 isoform PRMT1v2 promotes breast cancer cell survival and invasiveness. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3789. doi:10.1158/1538-7445.AM2013-3789
Fibre Optic Reflection Photometry on Blood
Authors: G. A. Mook, P. Osypka, R. E. Sturm, E. H. Wood
Journal: Cardiovascular Research (1968)

Journal Article Fibre Optic Reflection Photometry on Blood Get access Gerrit A. Mook, Gerrit A. Mook † From the Section of Physiology, Mayo Graduate School of Medicine, Rochester, Minnesota, U.S.A. † On leave from September 1963 to September 1964 from the Laboratory of Chemical Physiology, University of Groningen, the Netherlands. Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter Osypka, Peter Osypka From the Section of Physiology, Mayo Graduate School of Medicine, Rochester, Minnesota, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ralph E. Sturm, Ralph E. Sturm From the Section of Physiology, Mayo Graduate School of Medicine, Rochester, Minnesota, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Earl H. Wood Earl H. Wood From the Section of Physiology, Mayo Graduate School of Medicine, Rochester, Minnesota, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 2, Issue 2, April 1968, Pages 199–209, https://doi.org/10.1093/cvr/2.2.199 Published: 01 April 1968 Article history Received: 08 May 1967 Published: 01 April 1968
Prolonged His-Q interval in chronic bifascicular block. Relation to impending complete heart block.
Authors: Z Vera, D T Mason, R D Fletcher, N A Awan, R A Massumi
Journal: Circulation (1976)

Although prolonged infra-His conduction time in bifascicular block is suspected of denoting trifascicular disease, adquate documentation is lacking concerning the correlation between lengthened His-Q interval (H-Q) and the risk of development of complete heart block (CHB). H-Q in conducted sinus beats in patients with bifascicular block associated with Mobitz II or intermittent CHB represents the approximation of maximal H-Q prolongation prior to onset of trifascicular block. To assess this relationship between prolongation of H-Q and trifascicular block, His bundle electrocardiography (HBE) was performed in 50 patients with chronic bifascicular block exhibiting Mobitz II block or transient CHB. Mobitz II or episodic CHB was shown in all patients: within two days prior to HBE in 45/50 patients; in 39/50 patients during HBE; and following HBE in five patients. In 49/50 patients H-Q was prolonged (greater than 55 msec) and in 47 this interval was substantially lengthened (65 msec or greater). Since marked H-Q prolongation in conducted sinus beats was documented in nearly all patients with bifascicular block associated with intermittent complete trifascicular block, we conclude that a considerably lengthened H-Q interval in bifascicular block is not only a usual prerequisite but strong evidence, for impending complete heart block.
The effects of a cardioselective (metoprolol) and a nonselective (propranolol) beta-adrenergic blocker on the response to dynamic exercise in normal men.
Authors: J Sklar, G D Johnston, P Overlie, J G Gerber, H L Brammell, J Gal, A S Nies
Journal: Circulation (1982)

We compared the effects of a cardioselective beta-adrenergic blocking drug, metoprolol, with a nonselective beta-adrenergic blocker, propranolol, on the response of 10 normal men to dynamic treadmill exercise. The volunteers underwent a standard graded exercise test to exhaustion while receiving placebo; propranolol, 40 mg every 6 hours; propranolol, 80 mg every 6 hours; metoprolol, 50 mg every 6 hours; or metoprolol, 100 mg every 6 hours. The drugs were given in a double-blind fashion for 48 hours before exercise. Five days were allowed between successive drug administrations and the order of drug administration was randomized. Heart rate, arterial pressure, oxygen consumption, minute ventilation and CO2 production were monitored. Plasma drug concentrations were measured at the time of exercise. Judged by plasma levels, propranolol was about three times more potent than metoprolol in attenuating heart rate. Both drugs produced a wide variation in plasma levels after a given oral dose, and both drugs attenuated the systolic blood pressure response to exercise. Neither drug affected diastolic blood pressure or maximum oxygen consumption, maximum minute ventilation or the anaerobic threshold. We conclude that there is no evidence that the cardioselective drug metoprolol is superior to propranolol in terms of the ability to perform or respond to short-term maximal exercise. In addition, the fact that maximal oxygen consumption and the anaerobic threshold were unaffected implies that fatigue during exercise while on beta-adrenergic blocking drugs is not due to an effect of these drugs in limiting blood flow to the exercising extremities.
Operating Under the Threat of Chemical-Biological Warfare
Authors: Victor L. Modesto
Journal: JAMA (1991)

To the Editor.  —On January 20,1991, at 10:15 PM, while serving in the US Army for Operation Desert Storm, surgeons from the Eighth Evacuation Hospital (the first of the army's new Deployable Medical System [DEPMEDS] hospitals) were operating on a 23-year-old soldier for small-bowel obstruction from adhesions.  During the procedure, an explosion shook the operating theater, followed by warning sirens. Since this was the third night of Iraqi SCUD missile attacks, we were concerned that the hospital was under attack. Chemical protective masks were immediately donned; the surgeons and surgical technicians regowned and regloved while other members of the team put on their complete chemical protective suits, gloves, and boots. The air conditioning system was immediately turned off.  The procedure was completed uneventfully and the all-clear siren sounded as the incisional dressings were being applied. The patient had an uncomplicated postoperative recovery. The explosion was apparently a sonic boom from
Abstract PD01-08: Differences in estrogen receptor signaling in non-malignant primary ER-positive breast epithelial cells and breast cancer.
Authors: E Lim, HH He, D Chi, TY Yeung, S Schnitt, SX Liu, J Garber, A Richardson, M Brown
Journal: Cancer Research (2012)

Abstract Background: The estrogen receptor (ER) is expressed in ∼70% of sporadic breast cancer and activates genes driving cell proliferation and tumorigenesis. We have previously performed genome-wide analysis of ER binding sites in MCF-7 breast cancer cells, and identified distinct mechanisms of ER signaling. We have also previously used EpCAM and CD49f as markers to enrich for viable ER-positive (ER+) cells obtained from non malignant breast tissue. Here, we seek to elucidate differences in ER signaling between non-malignant and ER+ breast cancer cells. Methods: Primary breast epithelial cells were obtained from patients undergoing reduction mammoplasties and surgical excision of ER+ breast cancer. After dissociation of breast reductions into a single-cell suspension, ER+ mature luminal (ML; EpCAM+CD49f−) and luminal progenitor (LP; EpCAM+CD49f+) subpopulations were obtained by flow cytometry. Following estrogen stimulation, RNA was extracted for gene microarray analysis. ER chromatin immunoprecipitation and DNA sequencing (ChIP-seq) was performed. These results were compared to MCF-7 breast cancer cells. Results: Reduction mammoplasty and ER+ breast cancer tissues were analyzed, and compared to MCF-7 cells. Gene expression profiles were different between non-malignant tissue and ER+ breast cancer cells following estrogen stimulation, with a 2–3 fold higher number of ER regulated genes in ER+ breast cancer compared to ER+ non malignant cells, and few overlapping estrogen regulated genes. Genes that promotes cell cycling and cell proliferation were downregulated in non-malignant tissue, but were upregulated in breast cancer cells (P &amp;lt; 10–5). CYP1A1, a major estradiol metabolizing enzyme, was upregulated in normal cells but downregulated in ER+ breast cancer cells. Motif analysis of ER ChIP-seq data in normal and ER+ breast cancer tissues demonstrated an enrichment of ER motifs in the overlapping sites and an enrichment of FOXA1 motifs in ER+ breast cancer cells and TCF12 motifs in non-malignant ER+ epithelial cells. Conclusions: There are contrasting differences in ER signaling between normal mammary and breast cancer cells, with estrogen having anti-proliferative effects in normal luminal cells compared to pro-proliferative effects in breast cancer. ER ChIP-Seq has identified TCF12 as a major co-factor in non-malignant breast tissue whilst FOXA1 is a major co-factor in ER+ breast cancer. Our data provides evidence for key alterations in ER-signaling during tumorigenesis, and identifies potential mechanisms to target cancer specific ER signaling. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD01-08.
The ultrastructure of the human epidermis following ultracentrifugation
Authors: G.H. FINDLAY, N.v.d. W. LIEBENBERG
Journal: British Journal of Dermatology (1976)

Ultracentrifugation of the human epidermis was undertaken to uncover the forces responsible for the establishment and maintenance of the supranuclear melanin cap in basal cells. The wide spacing and elasticity of the tonofibrils caused a selective trapping of melanosomes in this region. At the same time the experiments produced pictures resembling dedifferentiation of the plasma membrane as in the fetal state, and differentiation of the tonofibrillar mass resembling the granular and horny layers. Once the tonofibrils had retracted and massed together, the order of intracellular sedimentation was: melanosome, chromatin, mitochondrion, tonofibril and ribosome.
Inhibition of Stathmin1 Accelerates the Metastatic Process
Authors: Karin Williams, Ritwik Ghosh, Premkumar Vummidi Giridhar, Guangyu Gu, Thomas Case, Scott M. Belcher, Susan Kasper
Journal: Cancer Research (2012)

Abstract The oncoprotein stathmin 1 (STMN1) is upregulated in most, if not all, cancers of epithelial cell origin; therefore STMN1 is considered a target for cancer therapy. However, its role during metastasis has not been investigated. Here, we report for the first time that STMN1 strongly inhibits metastatic behavior in both normal epithelial and cancerous epithelial cells. Initially, loss-of-STMN1 compromises cell–cell adhesion. This is followed by epithelial-to-mesenchymal transition (EMT), increased cell migration, and metastasis via cooperative activation of p38 and through TGF-β–independent and -dependent mechanisms. In contrast, expressing STMN1 restores cell–cell adhesion and reverses the metastatic cascade. Primary prostate epithelial cell cultures from benign to undifferentiated adenocarcinoma (UA) clinical biopsies show that EMT-like cells arise while the cancer is still organ-confined and that their emergence is tumor-stage specific. Furthermore, primary EMT-like cells exhibit metastatic behavior both in vitro and in vivo as compared with their non-EMT counterpart. These observations predict that using STMN1 as a generic therapeutic target might accelerate metastasis. Instead, there may be a tumor stage-specific window-of-opportunity in which conserving STMN1 expression is required to inhibit emergence of metastatic disease. Cancer Res; 72(20); 5407–17. ©2012 AACR.
Hepatocyte Growth Factor Sensitizes Brain Tumors to c-MET Kinase Inhibition
Authors: Ying Zhang, Kaitlyn E. Farenholtz, Yanzhi Yang, Fadila Guessous, Charles G. diPierro, Valerie S. Calvert, Jianghong Deng, David Schiff, Wenjun Xin, Jae K. Lee, Benjamin Purow, James Christensen, Emanuel Petricoin, Roger Abounader
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The receptor tyrosine kinase (RTK) c-MET and its ligand hepatocyte growth factor (HGF) are deregulated and promote malignancy in cancer and brain tumors. Consequently, clinically applicable c-MET inhibitors have been developed. The purpose of this study was to investigate the not-well-known molecular determinants that predict responsiveness to c-MET inhibitors and to explore new strategies for improving inhibitor efficacy in brain tumors. Experimental Design: We investigated the molecular factors and pathway activation signatures that determine sensitivity to c-MET inhibitors in a panel of glioblastoma and medulloblastoma cells, glioblastoma stem cells, and established cell line–derived xenografts using functional assays, reverse protein microarrays, and in vivo tumor volume measurements, but validation with animal survival analyses remains to be done. We also explored new approaches for improving the efficacy of the inhibitors in vitro and in vivo. Results: We found that HGF coexpression is a key predictor of response to c-MET inhibition among the examined factors and identified an ERK/JAK/p53 pathway activation signature that differentiates c-MET inhibition in responsive and nonresponsive cells. Surprisingly, we also found that short pretreatment of cells and tumors with exogenous HGF moderately but statistically significantly enhanced the antitumor effects of c-MET inhibition. We observed a similar ligand-induced sensitization effect to an EGF receptor small-molecule kinase inhibitor. Conclusions: These findings allow the identification of a subset of patients that will be responsive to c-MET inhibition and propose ligand pretreatment as a potential new strategy for improving the anticancer efficacy of RTK inhibitors. Clin Cancer Res; 19(6); 1433–44. ©2013 AACR.
Explaining human cognitive autapomorphies
Authors: Thomas Suddendorf
Journal: Behavioral and Brain Sciences (2008)

Abstract The real reason for the apparent discontinuity between human and nonhuman minds is that all closely related hominids have become extinct. Nonetheless, I agree with Penn et al. that comparative psychology should aim to establish what cognitive traits humans share with other animals and what traits they do not share, because this could make profound contributions to genetics and neuroscience. There is, however, no consensus yet, and Penn et al.'s conclusion that it all comes down to one trait is premature.
PREVENTION OF INTRACRANIAL AND INTRAVENOUS COMPLICATIONS IN SUPPURATIVE DISEASES OF THE EAR.
Authors: J. H. WOODWARD
Journal: JAMA (1901)

The predominant task of modern otology has been the evolution of an efficient treatment for mastoiditis and its complications. Formerly, surgical interference with the mastoid region was regarded as a formidable undertaking. In these days, however, we are accustomed to reports of mastoid disease in which cerebral abscesses have been evacuated, thrombosed intracranial sinuses opened and obliterated, and the internal jugular vein removed. Such cases exemplify surgical achievements of the highest order. We must not be dazzled by them, however, for it is a fair question whether there should be any cases of otitic cerebral abscess, or of otitic sinus-thrombosis, or of otitic pyemia. It seems to me that such complications are preventable, or, at least, that they may be relegated to the category of rare occurrences. The following observations are submitted as a contribution to the discussion of the ways and means by which the supervention of these complications
What Should Residents Know About Quality of Care?
Authors: Richard J. D. Pan
Journal: JAMA (1997)

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