tbuckley/cabot-search huggingface dataset:
Abstract A64: Cell-extrinsic effects of metformin in the breast cancer microenvironment
Authors: Christopher Charles Williams, Kabrina Miller
Journal: Cancer Research (2015)

Abstract Currently, few drugs have been formulated to disturb the autocrine/paracrine communication circuits which maintain the tumor-supportive microenvironment as a method of cancer chemoprevention. PGE2 (Prostaglandin E2) plays an important role in mediating the production of pro-inflammatory cytokines associated with tumor progression and metastasis. Recently, the anti-diabetic drug metformin has been associated with decreased incidence of several solid cancers among diabetic patients and has previously been shown to reduce expression of systemic inflammatory markers. However, few studies have detailed the intersection of metformin-mediated chemoprevention and chronic inflammation. As such, we investigated whether metformin impacts the inflammatory microenvironment in breast cancer to disrupt tumorigenesis and cancer progression. We hypothesize that metformin disrupts pro-neoplastic autocrine/paracrine inflammatory signaling by BCCs and its associated stroma. We have previously published that metformin inhibits proliferation of breast cancer cells, and that this impairment was associated with increased expression of growth differentiation factor 15 (GDF15) and repression of cyclooxygenase 1 mRNA expression. Here, we confirm that metformin decreases the intracellular and secreted GDF15 levels, and causes a reduction in the expression of proinflammatory annexin A2 protein, a component of the plasminogen receptor. Furthermore, exposure of breast cancer cells to metformin resulted in decreased PGE2 synthesis. Significantly, metformin mediated cell death was abrogated by addition of exogenous PGE2, suggesting that metformin at least in part elicits its antineoplastic function through PGE2 dependent mechanisms. Together these findings suggest a model in which metformin represses annexin A2 and cyclooxygenase expression, culminating in the loss of tumor-associated PGE2, induction of GDF15, and impaired breast cancer cell survival and invasiveness. As such, metformin may function to condition the pre-cancerous microenvironment/stroma to render it inhospitable toward further cancer progression. Citation Format: Christopher Charles Williams, Kabrina Miller. Cell-extrinsic effects of metformin in the breast cancer microenvironment. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A64. doi:10.1158/1538-7445.CHTME14-A64
Abstract 4704: Racial/ethnic differences in double-strand-break repair signaling in breast cancer
Authors: Jorge L. Rodriguez-Gil, Jeff W. Hill, Glenn O. Allen, Venetta Thomas, Jennifer J. Hu
Journal: Cancer Research (2010)

Abstract To evaluate whether deficient DNA repair contributes to elevated DNA damage and breast carcinogenesis, we used a newly developed flow-cytometry assay for rapid assessment of H2AX phosphorylation (gamma-H2AX) in response to double strand breaks (DSBs) in peripheral lymphocytes from 64 breast cancer cases and 71 controls. Basal or ionizing radiation (IR)-induced gamma-H2AX was not influenced by age, smoking status, family history (FH), age at menarche, age at first birth or parity and body mass index (BMI). With limited sample size, basal or IR-induced gamma-H2AX level did not differ between breast cancer cases (mean+SD, 6.65+1.18; 29.23+6.88) and controls (6.48+0.95; 27.19+7.26). In subgroup analysis of women with younger age at first live birth (&amp;lt;24), breast cancer cases have a significantly higher IR-induced gamma-H2AX level (29.87+6.45) than that in controls (26.60+7.19). In cases, African Americans (AA) had a significantly higher IR-induced gamma-H2AX level (32.17+6.76) than that in Caucasians (28.08+6.65), particularly in the younger age group (&amp;lt;50), never smokers, negative FH, and higher BMI (&amp;gt;25 kg/m2). In younger cases, a higher gamma-H2AX was observed in AA (p=0.042) compared to Caucasians (32.71+5.43 vs. 27.32+5.33). In never smokers, AA cases had a significantly higher level of IR-induced gamma-H2AX than Caucasians (32.70+5.77 vs. 27.58+6.41, p=0.03). In cases without FH, AA had a significantly higher level of IR-induced gamma-H2AX than Caucasians (32.38+6.90 vs. 28.02+7.09, p=0.044). In cases with a higher BMI, AA had a significantly higher level of IR-induced gamma-H2AX than Caucasians (33.36+5.94 vs. 26.93+6.00, p=0.001). Our results, although based on a relatively small group of subjects, indicate that DSBs response is significantly higher in AA breast cancer cases. Future larger studies are warranted to test whether this racial/ethnic difference in IR-induced gamma-H2AX levels contribute to breast cancer risk, tumor phenotypes, treatment response, and/or clinical outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4704.
Management of pregnancy in a woman with Hb H disease.
Authors: J M White, R W Jones
Journal: BMJ (1969)

Background/Aim: Targeting of the human epidermal growth factor receptor 2 (HER2) is suggested to be beneficial for esophageal squamous cell carcinoma (ESCC) patients with HER2 amplification. In this study, we evaluated the effects of combination chemotherapy with HER2-targeted drug trastuzumab in ESCC cells and examined the underlying mechanism contributing to these effects. Materials and Methods: HER2 expression was verified, and the efficacy of chemotherapy with and without trastuzumab was investigated in vitro and in vivo. Results: The combination of trastuzumab and a combined-modality therapy stimulated the PI3K/Akt pathway in ESCC cells overexpressing HER2. Trastuzumab treatment resulted in the intranuclear accumulation of FOXO3A in ESCC xenografts overexpressing HER2. The combination of trastuzumab and a combined-modality therapy enhanced antitumor effects in HER2-overexpressing ESCC xenografts. Conclusion: FOXO3A plays an important role in mediating the effects of trastuzumab, and combination chemotherapy may be a promising treatment for patients with HER2-overexpressing ESCC.
Cystic Disease of Renal Medulla
Authors: William M. Bennett, Norman Simon
Journal: Annals of Internal Medicine (1971)

Letters and Comments1 June 1971Cystic Disease of Renal MedullaWILLIAM M. BENNETT, M.D., NORMAN SIMON, M.D.WILLIAM M. BENNETT, M.D.Search for more papers by this author, NORMAN SIMON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-6-1011 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We read with interest the paper by Dr. Gardner in the January ANNALS (73:47-54, 1971) suggesting that cystic disease of the renal medulla in adults be distinguished from familial juvenile nephronophthisis on the bases of age of onset and an autosomal dominant mode of inheritance. In preparation is a report of a kindred, already published in abstract form (1), that does not support this separation.The proband in our kindred presented at age 22 with uremia and salt wasting and subsequently had pathological confirmation of renal medullary cysts, interstitial fibrosis, round cell infiltration, tubular atrophy, and periglomerular...References1. SIMONBENNETTWEINSTEIN NWR: Retinitis pigmentosa and salt wasting renal disease. International Congress of Nephrology Free Communications 1966, p. 274 Google Scholar2. MEIERHESS DJ: Familial nephropathy with retinitis pigmentosa: a new oculorenal syndrome in adults. Amer J Med 39:58-69, 1965 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAutosomal Dominant Tubulointerstitial Kidney DiseaseAutosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management—A KDIGO consensus report 1 June 1971Volume 74, Issue 6Page: 1011-1012KeywordsAtrophyAutosomal dominant diseasesFibrosisRenal diseasesSalts Issue Published: 1 June 1971 PDF downloadLoading ...
Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion
Authors: Patrick C. Hines, Qin Zen, Sharran N. Burney, Deborah A. Shea, Kenneth I. Ataga, Eugene P. Orringer, Marilyn J. Telen, Leslie V. Parise
Journal: Blood (2003)
Corticosteroid Therapy and Osteoporosis
Authors: A. B. Myles, P. A. Bacon, J. R. Daly, O. Savage
Journal: BMJ (1967)

In our work at the Pneumoconiosis Research Unit we actually used Indian ink instead of glycerol-water, as this gives a per- manent deposit on which differential counts can be made.In practice these turned out to be uninformative as the maximum drop- let size dominated the result, and it is a rather messy technique.In our studies we found an enormous range of performance, some nebulizers marketed by reputable firms having virtually no delivery and others producing dense clouds of droplets 20-30 microns in diameter.Inquiry among commercial firms produced no better account of test procedure than that given to Bruce by British Drug Houses.-Iam, etc.,
Novel Targets for Lung Cancer Therapy: Part I
Authors: Grace K. Dy, Alex A. Adjei
Journal: Journal of Clinical Oncology (2002)

Lung cancer is the second most common form of cancer in the United States, and although it accounts for 15% of all cancers, it is the most lethal, accounting for approximately 28% of cancer deaths. In 2002, it is estimated that 177,000 new cases of lung cancer will be diagnosed in the United States, and an estimated 160,000 men and women will die from the disease. This mortality rate is greater than that attributable to colorectal, breast, and prostate cancer combined. Systemic treatments for lung cancer with standard chemotherapy agents are still relatively ineffective. Agents targeting novel proliferative and survival pathways in lung cancer are needed to improve treatment outcomes. In recent years, numerous agents inhibiting aberrant processes in tumor cells have undergone clinical evaluation. This review is the first of a two-part series that summarizes pertinent preclinical and clinical information on novel drugs that target critical abnormalities in lung cancer. In this article, agents inhibiting growth factor receptors and various molecules downstream of activated signaling cascades, such as cytoplasmic second messengers, are described.
Herpes gestationis factor reacts with the amniotic epithelial basement membrane
Authors: J.-P. ORTONNE, B.-L. HSI, P. VERRANDO, F. BERNERD, G. PAUTRAT, A. PISANI, C.-J.G. YEH
Journal: British Journal of Dermatology (1987)

Journal Article Herpes gestationis factor reacts with the amniotic epithelial basement membrane Get access J.‐P. ORTONNE, J.‐P. ORTONNE Professor Jean‐Paul Ortonne, Service de Dermatologie, Hôpital Pasteur, 06000 Nice, France. Search for other works by this author on: Oxford Academic Google Scholar B.‐L. HSI, B.‐L. HSI INSERM U2IO, Faculté de Médecinc, Sophia Antipolis, Valbonne, France. Search for other works by this author on: Oxford Academic Google Scholar P. VERRANDO, P. VERRANDO Service de Dermatologie, Hôpital Pasteur, Nice, Sophia Antipolis, Valbonne, France. Search for other works by this author on: Oxford Academic Google Scholar F. BERNERD, F. BERNERD CIRD, Sophia Antipolis, Valbonne, France. Search for other works by this author on: Oxford Academic Google Scholar G. PAUTRAT, G. PAUTRAT CIRD, Sophia Antipolis, Valbonne, France. Search for other works by this author on: Oxford Academic Google Scholar A. PISANI, A. PISANI Service de Dermatologie, Hôpital Pasteur, Nice, Sophia Antipolis, Valbonne, France. Search for other works by this author on: Oxford Academic Google Scholar C.‐J.G. YEH C.‐J.G. YEH INSERM U2IO, Faculté de Médecinc, Sophia Antipolis, Valbonne, France. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 2, 1 August 1987, Pages 147–154, https://doi.org/10.1111/j.1365-2133.1987.tb04110.x Published: 01 August 1987
Effect of Central Catecholamine Depletion on the Osmotic and Nonosmotic Stimulation of Vasopressin (Antidiuretic Hormone) in the Rat
Authors: Thomas R. Miller, William A. Handelman, Patricia E. Arnold, Keith M. McDonald, Perry B. Molinoff, Robert W. Schrier
Journal: Journal of Clinical Investigation (1979)

The central nervous system (CNS) mechanism(s) for the release of antidiuretic hormone (ADH) by various stimuli is unknown. In this study, the role of CNS catecholamines in effecting ADH release was examined in conscious rats 10-14 d after the cerebroventricular injection of 6-hydroxydopamine (6-OHDA). This dose of 6-OHDA caused a 67% depletion of brain tissue norepinephrine and only 3% depletion of heart norepinephrine, as compared with controls, which were injected with the vehicle buffer alone. Either intravenous 3% saline (osmotic stimulus) or intraperitoneal hyperoncotic dextran (nonosmotic stimulus) was administered to water-diuresing rats through indwelling catheters. Neither of these maneuvers changed arterial pressure, pulse, or inulin clearance in control or 6-OHDA rats. The 3% saline caused similar increases in plasma osmolality (15 mosmol/kg H2O) in control and 6-OHDA rats. The control rats, however, increased urinary osmolality (Uosm) to 586 mosmol/kg H2O, whereas 6-OHDA rats increased Uosm only to 335 mosmol/kg H2O (P < 0.005). These changes in Uosm were accompanied by an increase in plasma ADH to 7.6 μIU/ml in control animals vs. 2.9 μIU/ml in 6-OHDA rats (P < 0.005). All waterdiuresing animals had undetectable plasma ADH levels. Dextran-induced hypovolemia caused similar decrements (− 10%) in blood volume in both control and 6-OHDA animals, neither of which had significant changes in plasma osmolality. This nonosmotic hypovolemic stimulus caused an increase in Uosm to 753 mosmol/kg H2O in control rats, whereas Uosm in 6-OHDA rats increased to only 358 mosmol/kg H2O (P < 0.001). At the same time, ADH levels also were significantly greater in Cont rats (2.4 μIU/ml) than in the 6-OHDA animals (0.69 μIU/ml; P < 0.05). These results therefore suggest that CNS catecholamines may play an important role in mediating ADH release in response to both osmotic and nonosmotic (hypovolemic) stimuli.
Alloalbuminemia. Albumin Naskapi in Indians of the Ungava
Authors: B. S. Blumberg
Journal: JAMA (1968)

Alloalbuminemia is a condition in which the individual has an albumin variant different from common albumin (albumin A). Clinical examinations were performed on Naskapi and Montagnais Indians homozygous and heterozygous for an inherited albumin variant, albumin Naskapi, common in several North American Indian tribes but absent in other populations. None of the individuals with albumin Naskapi appears to have clinical or laboratory findings which could be ascribed to alloalbuminemia. Many physiological materials, dyes, and drugs bind to serum albumin, and some of these bind differentially to the albumin variants. This could be of clinical importance in American Indians.
Primary Mother Care and Population
Authors: T. McMichael
Journal: BMJ (2003)

![][1] 

Eds Glen Mola, Jim Thornton, Michael Breen, Colin Bullough, John Guillebaud, Frank Addo

Published privately by Maurice King, pp 416 ISBN pp 416 ISBN 0 9544212 0 5. For information about price and ordering, email sales@spiegl.co.uk or telephone + 44 (0)1780 762550

www.leeds.ac.uk/demographic.disentrapment/

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A remarkable thing about Maurice King is his ingenuity in getting his controversial ideas into print. Motivated by public health and humanitarian concerns, he has long pursued a well researched, passionate, somewhat eccentric, and tireless campaign to avert demographic and environmental disaster in an increasingly overpeopled, overconsuming world. Now entering the fourth quarter of his first century, after several decades of engagement and leadership in primary health care in developing countries, King has reinvented himself as “knowledge engineer,” a sort of literary puppeteer. The editors of this book, all colleagues from his years of work and travel, have contributed ideas and critiques. King, however, has done much of the writing and design.

The …

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Frida Kahlo de Rivera Symposium
Authors: Leo Eloesser
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Frida Kahlo de Rivera, than whom no painter ever more successfully transferred his (or her) emotions to canvas, would, were she able, reject your designation of her as a European, with a whirlwind of protest. Though her father was a German-born photographer, her mother was Mexican; she herself was born and bred a Mexican; and passionately Mexican she lived. As for the painting's intending "to illustrate the transfusion of cultures which the marriage epitomized"—guess again!
The supernatural guilt trip does not take us far enough
Authors: Nathalia L. Gjersoe, Bruce M. Hood
Journal: Behavioral and Brain Sciences (2006)

Belief in souls is only one component of supernatural thinking in which individuals infer the presence of invisible mechanisms that explain events as paranormal rather than natural. We believe it is important to place greater emphasis on the prevalence of supernatural beliefs across other domains, if only to counter simplistic divisions between rationality and irrationality recently aligned with the contentious science/religion debate.
Thyroid Hormone Transport and Utilization.
Authors: S. H. Ingbar
Journal: Annals of Internal Medicine (1962)

s1 April 1962Thyroid Hormone Transport and Utilization.S. H. Ingbar, M.D.S. H. Ingbar, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-675_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFollowing its release from the thyroid gland, thyroxine enters into a reversible binding equilibrium with specific plasma proteins. As a result of these interactions, only a small proportion of the hormone remains free or unbound, while the remainder acquires macromolecular characteristics which profoundly influence its subsequent metabolism. Evidence indicates that it is the unbound hormone which is available to tissues for metabolic action, degradation, or excretion, while the bound hormone may be metabolically inert. Changes in the protein-hormone interaction, resulting from alterations in the concentration of either thyroxine or its binding sites, alter the proportion of the unbound thyroxine and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Mass. (BS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 675-675KeywordsAttentionExcretionHormonesPlasma proteinsThyroidThyroid hormonesThyroxine Issue Published: 1 April 1962 PDF DownloadLoading ...
Book Review Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, diagnosis, management Sixth edition. Edited by Mark Feldman, Bruce F. Scharschmidt, and Marvin H. Sleisenger, with Samuel Klein. 2046 pp. in two volumes, illustrated. Philadelphia, W.B. Saunders, 1998. $195. 0-7216-6291-9
Authors: C.N. Ghent
Journal: New England Journal of Medicine (1998)
Rapid glutamate receptor 2 trafficking during retinal degeneration
Authors: Yanhua Lin, Bryan W Jones, Aihua Liu, Félix R Vazquéz-Chona, J Scott Lauritzen, W Drew Ferrell, Robert E Marc
Journal: Molecular Neurodegeneration (2012)

Retinal degenerations, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), are characterized by photoreceptor loss and anomalous remodeling of the surviving retina that corrupts visual processing and poses a barrier to late-stage therapeutic interventions in particular. However, the molecular events associated with retinal remodeling remain largely unknown. Given our prior evidence of ionotropic glutamate receptor (iGluR) reprogramming in retinal degenerations, we hypothesized that the edited glutamate receptor 2 (GluR2) subunit and its trafficking may be modulated in retinal degenerations.Adult albino Balb/C mice were exposed to intense light for 24 h to induce light-induced retinal degeneration (LIRD). We found that prior to the onset of photoreceptor loss, protein levels of GluR2 and related trafficking proteins, including glutamate receptor-interacting protein 1 (GRIP1) and postsynaptic density protein 95 (PSD-95), were rapidly increased. LIRD triggered neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites. Immunoprecipitation analysis showed interaction between KIF3A and GRIP1 as well as PSD-95, suggesting that KIF3A may mediate transport of GluR2 and its trafficking proteins to the novel dendrites. However, in areas of photoreceptor loss, GluR2 along with its trafficking proteins nearly vanished in retracted retinal neurites.All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.
Treatment of Renal Failure in a Unit with Facilities for Haemodialysis (Twin-coil Artificial Kidney)
Authors: R. C. Jackson, N. V. D. Bunker, W. J. Elder, A. M. Joekes
Journal: BMJ (1960)

MEDICAL JOUJRNAL 10 and varying signs of precocious puberty and virilization.After puberty defeminization merging into virilization occurs and the clitoris rarely exceeds 1 cm. in diameter.
Large deletion of the X‐linked lymphoproliferative disease gene detected by fluorescence in situ hybridization
Authors: K. Honda, H. Kanegane, M. Eguchi, H. Kimura, T. Morishima, K. Masaki, G. Tosato, T. Miyawaki, E. Ishii
Journal: American Journal of Hematology (2000)

The X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by an abnormal responses to infection with Epstein-Barr virus (EBV), resulting in fatal infectious mononucleosis, hypogammaglobulinemia, virus-associated hemophagocytic syndrome, and malignant lymphoma. Mutations in the gene coding for a T cell-specific SLAM-associated protein (SAP) have been recently identified in XLP patients. We report on a 1-year-old boy representing fulminant hemophagocytic syndrome. He developed high fever, lymphadenopathy, hepatosplenomegaly with liver dysfunction, and pancytopenia with marrow hemophagocytosis. EBV DNA was abnormally increased in the blood. Polymerase chain reaction failed to amplify SAP mRNA and genomic DNA products from the patient' As peripheral blood. A large deletion of the SAP gene was confirmed by fluorescence in situ hybridization (FISH). FISH analysis also disclosed that the patient's mother was a carrier. We conclude that FISH can be useful in the diagnosis of XLP with large deletions of the SAP gene and its carrier state.