tbuckley/cabot-search huggingface dataset:
The trophic action of growth hormone, insulin-like growth factor-I, and insulin on human duodenal mucosa cultured in vitro.
Authors: E E Wheeler, D N Challacombe
Journal: Gut (1997)

BACKGROUND: Experimental evidence suggests that hormones may regulate small intestinal adaptation after surgical resection. AIMS: To characterise the effect of recombinant human growth hormone (GH), insulin-like growth factor-I (IGF-I) and insulin on crypt epithelial cell proliferation in the human duodenal mucosa cultured in vitro. PATIENTS: Thirty nine adults had endoscopic duodenal biopsy specimens taken, which were histologically normal and pair matched specimens from each patient acted as their own control. METHODS: Paired biopsy specimens from patients were cultured in vitro, with or without the addition of GH (0.004 IU/ml), IGF-I (400 ng/ml) or insulin (50 micrograms/ml), alone or in combination. After 22 hours, vincristine sulphate was added to the cultures and three hours later specimens were removed and fixed, and DNA stained by the Feulgen method. Intestinal crypts were microdissected and crypt epithelial cell proliferation determined by estimating mean numbers of accumulated metaphase arrests/crypt present in tests and controls between 22-25 hours of culture. RESULTS: The addition of GH, IGF-I, and insulin, alone or in combination, significantly increased crypt epithelial cell proliferation in test explants compared with controls. IGF-I was most potent and its trophic effect was modified by insulin. CONCLUSIONS: GH, IGF-I, and insulin are involved in the regulation of crypt cell proliferation in the human small intestine in vitro and possibly in vivo.
Primary structure and functional expression of a mammalian skeletal muscle sodium channel
Authors: James S. Trimmer, Sharon S. Cooperman, Sally A. Tomiko, Jiuying Zhou, Shelia M. Crean, Mary B. Boyle, Roland G. Kalen, Zuhang Sheng, Robert L. Barchi, Frederick J. Sigworth, Richard H. Goodman, William S. Agnew, Gail Mandel
Journal: Neuron (1989)
New Activity of Spironolactone
Authors: Nancy Klauber, Fiona Browne, Bela Anand-Apte, Robert J. D'Amato
Journal: Circulation (1996)

Background The formation of new blood vessels (angiogenesis) is a critical component in a variety of pathological settings, including solid tumor growth, macular degeneration, and atherosclerosis. Methods and Results We have found that orally administered spironolactone inhibited the area of angiogenesis induced by basic fibroblast growth factor (bFGF) in a rabbit corneal micropocket assay. Additionally, spironolactone inhibited bFGF- and vascular endothelial growth factor–stimulated capillary endothelial cell proliferation in vitro, inhibited bFGF-stimulated capillary endothelial cell chemotaxis in vitro, and caused avascular zones when placed on the chick chorioallantoic membrane. Experiments analyzing spironolactone metabolites revealed that the major human metabolites 6β-hydroxy-7α-thiomethyl spironolactone and canrenoic acid retained antiangiogenic activity. The antiangiogenic activity appears to be unrelated to the antiandrogenic and antimineralocorticoid effects of spironolactone. Conclusions These experiments hold promise for the potential use of spironolactone as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.
A review of human carcinogens—Part C: metals, arsenic, dusts, and fibres
Authors: Kurt Straif, Lamia Benbrahim-Tallaa, Robert Baan, Yann Grosse, Béatrice Secretan, Fatiha El Ghissassi, Véronique Bouvard, Neela Guha, Crystal Freeman, Laurent Galichet, Vincent Cogliano
Journal: The Lancet Oncology (2009)
Silencing Survivin Splice Variant 2B Leads to Antitumor Activity in Taxane-Resistant Ovarian Cancer
Authors: Pablo E. Vivas-Mejia, Cristian Rodriguez-Aguayo, Hee-Dong Han, Mian M.K. Shahzad, Fatma Valiyeva, Mineko Shibayama, Arturo Chavez-Reyes, Anil K. Sood, Gabriel Lopez-Berestein
Journal: Clinical Cancer Research (2011)

Abstract Purpose: To study the role of survivin and its splice variants in taxane-resistant ovarian cancer. Experimental Design: We assessed the mRNA levels of survivin splice variants in ovarian cancer cell lines and ovarian tumor samples. siRNAs targeting survivin were designed to silence all survivin splice variants (T-siRNA) or survivin 2B (2B-siRNA) in vitro and orthotopic murine models of ovarian cancer. The mechanism of cell death was studied in taxane-resistant ovarian cancer cells and in tumor sections obtained from different mouse tumors. Results: Taxane-resistant ovarian cancer cells express higher survivin mRNA levels than their taxane-sensitive counterparts. Survivin 2B expression was significantly higher in taxane-resistant compared with -sensitive cells. Silencing survivin 2B induced growth inhibitory effects similar to silencing total survivin in vitro. In addition, survivin 2B-siRNA incorporated into DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) nanoliposomes resulted in significant reduction in tumor growth (P &amp;lt; 0.05) in orthotopic murine models of ovarian cancer, and these effects were similar to T-siRNA-DOPC. The antitumor effects were further enhanced in combination with docetaxel chemotherapy (P &amp;lt; 0.01). Finally, we found a significant association between survivin 2B expression and progression-free survival in 117 epithelial ovarian cancers obtained at primary debulking surgery. Conclusions: These data identify survivin 2B as an important target in ovarian cancer and provide a translational path forward for developing new therapies against this target. Clin Cancer Res; 17(11); 3716–26. ©2011 AACR.
Paracrine Hedgehog Signaling in Cancer
Authors: Jan-Willem Theunissen, Frederic J. de Sauvage
Journal: Cancer Research (2009)

Abstract Ligand-dependent and ligand-independent activation of the Hedgehog (Hh) signaling pathway is involved in tumorigenesis. The importance of mutations in Hh pathway components leading to constitutive signaling has been well established in basal cell carcinoma and medulloblastoma. However, the role of ligand-driven Hh pathway activation in cancer remains to be established. Three recent articles support a model in which, in the absence of mutations in the Hh pathway, Hh ligands expressed by a subset of epithelial cancers, including colon, pancreatic, and ovarian cancer, promote tumor growth indirectly by activating Hh signaling in the surrounding stroma, which, in turn, provides a more favorable environment for tumor growth. These data have important implications for the use of Hh pathway inhibitors currently in development and for selection of tumors likely to respond to such inhibitors. [Cancer Res 2009;69(15):6007–10]
Ring avulsion injuries and the basketball player.
Authors: B R Pynn, T P Bartkiw, H M Clarke
Journal: British Journal of Sports Medicine (1997)

As basketball increases in worldwide popularity, more epidemiological data on injury rate and type will be documented. A serious ring avulsion injury (Urbaniuk Class I) is here reported in an adolescent incurred while attempting a slam dunk. The management of this injury is discussed as well as safety concerns for coaches and supervisory staff.
Head and neck melanoma: pattern of sun exposure and histological subtypes
Authors: N.R. Attard
Journal: British Journal of Dermatology (2015)

Journal Article Head and neck melanoma: pattern of sun exposure and histological subtypes Get access N.R. Attard N.R. Attard St John's Institute of Dermatology Guy's and St Thomas’ NHS Foundation Trust Great Maze Pond London SE1 9RT U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 3, 1 March 2015, Pages 560–561, https://doi.org/10.1111/bjd.13659 Published: 01 March 2015
Putrid gums and 'Dead Men's Cloaths': James Lind aboard the Salisbury
Authors: G. Sutton
Journal: Journal of the Royal Society of Medicine (2003)

18th century sailors often suffered from scurvy.In 1747 James Lind conducted his classic experiments aboard the Salisbury, in which he cured scurvy with oranges and lemons.The Royal Navy did not introduce citrus rations until 1795.The original ship's papers allow the circumstances of the experiment to be reconstructed.The relevant patrol began in March 1747, and Lind's experiment began after 8 weeks at sea.The muster roll records almost no sickness aboard until the ship returned to Plymouth in June.This is at odds with Lind's account and suggests an antisickness official culture, which may have contributed to the neglect of his work.
Management of breast cancer in elderly individuals: recommendations of the International Society of Geriatric Oncology
Authors: Hans Wildiers, Ian Kunkler, Laura Biganzoli, Jacques Fracheboud, George Vlastos, Chantal Bernard-Marty, Arti Hurria, Martine Extermann, Véronique Girre, Etienne Brain, Riccardo A Audisio, Harry Bartelink, Mary Barton, Sharon H Giordano, Hyman Muss, Matti Aapro
Journal: The Lancet Oncology (2007)
Parallel Evolution of an Enzyme Family in Plants and Animals May Signal Coevolution of Consumed and Consumer
Authors: J. Caspermeyer
Journal: Molecular Biology and Evolution (2014)

Crab Nebula of LifeCrabs-those sometimes pesky, hard-shelled beachcombers-are a highly diverse animal, with some 7,000 species found in oceans, lakes, and on land, varying in size from the diminutive pea crab (millimeters) to the giant 4-m wide Japanese spider crab.Tsang et al. ( 2014) have constructed the most complete and extensive data set to date.Their recalibrated crab gene tree using DNA and mitochondrial sequences from 140 species and 58 crab families provides some new important insights into the timing and diversity of crab evolution.The research team's estimates confirm the fossil record of most living crab families and superfamilies first arising during the late Cretaceous and early Tertiary (60-100 Ma), at the same time when dinosaurs ruled the Earth.They also demonstrated that freshwater crabs were derived early in the evolution of true crabs and are shown to have at least two independent origins.Molecular methods estimate that
Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells
Authors: Sofia Winslow, Karin Leandersson, Christer Larsson
Journal: Molecular Cancer (2013)

Abstract Background Regulation of mRNAs is one way to control protein levels and thereby important cellular processes such as growth, invasion and apoptosis. G3BPs constitute a family of mRNA-binding proteins, shown to be overexpressed in several cancer types, including breast, colon and pancreas cancer. G3BP has been reported to both stabilize and induce degradation of specific mRNAs. Results Here, we show that G3BP1, but not G3BP2, supports proliferation of several breast cancer cell lines. Global gene expression analyses of G3BP1- and G3BP2-depleted cells indicate that primarily G3BP1, and much less G3BP2, influences mRNA expression levels. Peripheral myelin protein 22 (PMP22) was one gene that was significantly influenced by G3BP1 depletion which led to a 2–3 fold increased expression . Depletion of PMP22 resulted in increased proliferation and the G3BP1-mediated effect on proliferation was not seen upon PMP22-depletion. Conclusions This indicates a novel role for G3BP1 in the regulation of cell proliferation in breast cancer cells, perhaps via a regulatory effect on PMP22 expression.
Life Span of Carbamylated Red Cells in Sickle Cell Anemia
Authors: Paul F. Milner, Samuel Charache
Journal: Journal of Clinical Investigation (1973)

By using three isotopes of diisopropyl-phosphofluoridate ([(3)H]-, [(14)C]-, and [(32)P]DFP) simultaneously, the life span of red cells from 20 patients with sickle cell anemia (Hb SS) has been studied after varying degrees of carbamylation in vitro with cyanate (NCO) and carbamyl phosphate (CP). The results are expressed in terms of the red cell mean life span (MLS). The MLS of red cells in the patients studied averaged 15.2+/-6.3 (SD) days. After carbamylation the increase in red cell life span was linearly proportional to the concentration of cyanate used, so that at 0.01. 0.02, and 0.3 M NCO (approximately 1, 1.6, and 2 mol NCO/mol Hb) the average increase in MLS was 8.14+/-4.9 days, 14.7+/-4.1 days, and 18.4+/-8.8 days, respectively. Analysis of survival curves and the results of an experiment using a population of Hb SS cells separated by centrifugation indicated that carbamylation had a disproportionate effect on the survival of the youngest cells in the population. Improvement in MLS correlated with the reticulocyte count of the cells carbamylated. This finding is explained on the hypothesis that the life span of irreversibly sickled and other damaged cells is not improved by carbamylation but that carbamylation greatly improves the life span of the young, and as yet undamaged, cells. For this reason extracorporeal carbamylation is not favored as a form of therapy. At the level of carbamylation attainable by oral therapy, however, it would appear likely that only a modest increase in red cell life span will be achieved.
Erratum to “Hepatocyte growth factor-induced proliferation of hepatic stem-like cells depends on activation of NF-κB” [J Hepatol 40 (2004) 391–398]
Authors: Peng Yao, Yiqun Zhan, Wangxiang Xu, Changyan Li, Peibin Yue, Chengwang Xu, Darong Hu, Cheng-Kui Qu, Xiaoming Yang
Journal: Journal of Hepatology (2004)
Impaired monocyte‐macrophage functions and defective toll‐like receptor signaling in hepatitis E virus‐infected pregnant women with acute liver failure
Authors: Rashi Sehgal, Sharda Patra, Paul David, Ashish Vyas, Arshi Khanam, Syed Hissar, Ekta Gupta, Guresh Kumar, Shyam Kottilil, Rakhi Maiwall, Shiv Kumar Sarin, Nirupama Trehanpati
Journal: Hepatology (2015)

Acute viral hepatitis resulting due to hepatitis E viral infection (AVH‐E) is often serious in pregnancy and could result in acute liver failure (ALF). The role of monocytes and macrophages (mono‐macs) in the pathogenesis of AVH‐E and development of ALF‐E in pregnancy is unclear. We investigated the functions of mono‐macs in pregnant (P), AVH‐E (n = 44), ALF‐E (n = 12), healthy controls (HC; n = 20) and compared with nonpregnant (NP) AVH‐E (n = 10), ALF‐E (n = 5), and HC (n = 10). We also recruited non‐hepatitis E virus‐related pregnant (P), ALF‐NE (n = 5) and non‐pregnant (NP), ALF‐NE (n = 12) patients with ALF. Mono‐macs, dendritic cell (DC) phenotypes, and Toll‐like receptor (TLR) expressions were studied by flow cytometry and reverse‐transcriptase polymerase chain reaction. Mono‐macs functionality was determined by analyzing their phagocytic activity and reactive oxygen species (ROS) generation by using flow cytometry. Frequency of mono‐macs and DCs was increased during HEV infection compared to HC ( P &lt; 0.001). Macrophages were increased ( P &lt; 0.002) in ALF‐E(P) compared to ALF‐NE(P). The macrophage phagocytic activity and Escherichia coli ‐induced ROS production was significantly impaired in ALF‐E(P) compared to AVH‐E(P) ( P &lt; 0.001), ALF‐E(NP), and ALF‐NE(P) patients ( P &lt; 0.02). TLR3 and TLR9 expression and downstream MYD88 signalling molecules IRF3 and IRF7 were significantly down‐regulated in ALF‐E(P) ( P &lt; 0.00) compared to AVH‐E(P) and ALF‐NE(P). Conclusion: Functionality of mono‐macs is impaired in pregnant ALF‐E patients compared to AVH‐E(P). Reduced TLR3 and TLR7 expression and TLR downstream‐signaling molecules in pregnant ALF‐E patients suggests inadequate triggers for the innate immune responses contributing to development and severity of ALF‐E. Studies using TLR agonists to activate mono‐macs may be of use and in vitro studies should be undertaken using patient samples.(H epatology 2015;62:1683–1696)
The Numbers Are In
Authors: Claire S. Duvernoy, Roger Blumenthal
Journal: Circulation (2010)

I n this issue of Circulation, Mora et al demonstrate for the first time that statins are effective for the primary prevention of cardiovascular events in women. 1 Under a prespecified analysis, the authors examined sex-specific outcomes in JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), which enrolled 6801 women Ն60 years old and 11 001 men Ն50 years old without prior history of coronary heart disease, diabetes mellitus, or stroke who had low-density lipoprotein cholesterol (LDL-C) Ͻ130 mg/dL and high-sensitivity C-reactive protein (hsCRP) Ն2.0 mg/L.
Cadherins, RhoA, and Rac1 Are Differentially Required for Stretch-Mediated Proliferation in Endothelial Versus Smooth Muscle Cells
Authors: Wendy F. Liu, Celeste M. Nelson, John L. Tan, Christopher S. Chen
Journal: Circulation Research (2007)

Abnormal mechanical forces can trigger aberrant proliferation of endothelial and smooth muscle cells, as observed in the progression of vascular diseases such as atherosclerosis. It has been previously shown that cells can sense physical forces such as stretch through adhesions to the extracellular matrix. Here, we set out to examine whether cell-cell adhesions are also involved in transducing mechanical stretch into a proliferative response. We found that both endothelial and smooth muscle cells exhibited an increase in proliferation in response to stretch. Using micropatterning to isolate the role of cell-cell adhesion from cell-extracellular matrix adhesion, we demonstrate that endothelial cells required cell-cell contact and vascular endothelial cadherin engagement to transduce stretch into proliferative signals. In contrast, smooth muscle cells responded to stretch without contact to neighboring cells. We further show that stretch stimulated Rac1 activity in endothelial cells, whereas RhoA was activated by stretch in smooth muscle cells. Blocking Rac1 signaling by pharmacological or adenoviral reagents abrogated the proliferative response to stretch in endothelial cells but not in smooth muscle cells. Conversely, blocking RhoA completely inhibited the proliferative response in smooth muscle cells but not in endothelial cells. Together, these data suggest that vascular endothelial cadherin has an important role in mechanotransduction and that endothelial and smooth muscle cells use different mechanisms to respond to stretch.
ACE in COPD: a therapeutic target?
Authors: R Forth
Journal: Thorax (2003)

Chronic lowering of ACE activity may have profound benefits in the long term treatment of patients with chronic lung disease such as COPD.

As a component of the circulating (or endocrine) renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) plays an important role in circulatory homeostasis. ACE cleaves angiotensin I to yield the potent vasopressor octapeptide angiotensin II while simultaneously cleaving vasodilator kinins, and angiotensin II drives renal salt/water retention through release of adrenal aldosterone. In this way, ACE exerts tonic influence on water balance and blood pressure. However, local cellular (autocrine) and organ (paracrine) RAS exist in tissues as diverse as human heart,1 skeletal muscle,2 fat,3 and brain,4 where they play a variety of roles. Whether in the circulation or the tissues,1,5 the presence (insertion, I allele) rather than the absence (deletion, D allele) of a 287 base pair fragment in the human ACE gene is associated with increased ACE activity.

Increasing RAS activity certainly exerts powerful proinflammatory effects in many systems,6–10 while angiotensin II has direct profibrotic actions.11 Local RAS has …
Combating the Threat of Pandemic Influenza: Drug Discovery Approaches
Authors: W. Paul Glezen
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sir Thomas Browne's birthday
Authors: C. Morris
Journal: Journal of the Royal Society of Medicine (2005)

The mistaken belief that Sir Thomas Browne was born on 19 October 1605, exactly 77 years before his death, originated in the anonymous biography preceding Browne's Posthumous Works,1 which included his musings on such a rare coincidence of dates. It gathered credence by frequent repetition, as in Professor Breathnach's appreciative memoir (January 2005, JRSM2), and has endured for nearly 300 years. Yet it should have been abandoned by now.3 Sir Thomas himself, in answer to John Aubrey's request, wrote on 24 August 1672: 'I was borne Novemb. 19, 1605'.4 There is no reason to doubt his word, which was accepted by Anthony Wood for the first biography5 and is affirmed in the recent Oxford Dictionary of National Biography.6
Validation, revision and extension of the Follicular Lymphoma International Prognostic Index (FLIPI) in a population-based setting
Authors: S.A.M. van de Schans, E.W. Steyerberg, M.R. Nijziel, G.-J. Creemers, M.L. Janssen-Heijnen, D.J. van Spronsen
Journal: Annals of Oncology (2009)
Random migration precedes stable target cell interactions of tumor-infiltrating T cells
Authors: Paulus Mrass, Hajime Takano, Lai Guan Ng, Sachin Daxini, Marcio O. Lasaro, Amaya Iparraguirre, Lois L. Cavanagh, Ulrich H. von Andrian, Hildegund C.J. Ertl, Philip G. Haydon, Wolfgang Weninger
Journal: The Journal of Experimental Medicine (2006)

The tumor microenvironment is composed of an intricate mixture of tumor and host-derived cells that engage in a continuous interplay. T cells are particularly important in this context as they may recognize tumor-associated antigens and induce tumor regression. However, the precise identity of cells targeted by tumor-infiltrating T lymphocytes (TILs) as well as the kinetics and anatomy of TIL-target cell interactions within tumors are incompletely understood. Furthermore, the spatiotemporal conditions of TIL locomotion through the tumor stroma, as a prerequisite for establishing contact with target cells, have not been analyzed. These shortcomings limit the rational design of immunotherapeutic strategies that aim to overcome tumor-immune evasion. We have used two-photon microscopy to determine, in a dynamic manner, the requirements leading to tumor regression by TILs. Key observations were that TILs migrated randomly throughout the tumor microenvironment and that, in the absence of cognate antigen, they were incapable of sustaining active migration. Furthermore, TILs in regressing tumors formed long-lasting (≥30 min), cognate antigen–dependent contacts with tumor cells. Finally, TILs physically interacted with macrophages, suggesting tumor antigen cross-presentation by these cells. Our results demonstrate that recognition of cognate antigen within tumors is a critical determinant of optimal TIL migration and target cell interactions, and argue against TIL guidance by long-range chemokine gradients.