tbuckley/cabot-search huggingface dataset:
Cancer-Associated Adipose Tissue Promotes Breast Cancer Progression by Paracrine Oncostatin M and Jak/STAT3 Signaling
Authors: Lore Lapeire, An Hendrix, Kathleen Lambein, Mieke Van Bockstal, Geert Braems, Rudy Van Den Broecke, Ridha Limame, Pieter Mestdagh, Jo Vandesompele, Christian Vanhove, Dawn Maynard, Camille Lehuédé, Catherine Muller, Philippe Valet, Christian P. Gespach, Marc Bracke, Veronique Cocquyt, Hannelore Denys, Olivier De Wever
Journal: Cancer Research (2014)

Increasing evidence supports the critical roles played by adipose tissue in breast cancer progression. Yet, the mediators and mechanisms are poorly understood. Here, we show that breast cancer-associated adipose tissue from freshly isolated tumors promotes F-actin remodeling, cellular scattering, invasiveness, and spheroid reorganization of cultured breast cancer cells. A combination of techniques, including transcriptomics, proteomics, and kinomics enabled us to identify paracrine secretion of oncostatin M (OSM) by cancer-associated adipose tissue. Specifically, OSM, expressed by CD45(+) leucocytes in the stromal vascular fraction, induced phosphorylation of STAT3 (pSTAT3-) Y705 and S727 in breast cancer cells and transcription of several STAT3-dependent genes, including S100 family members S100A7, S100A8, and S100A9. Autocrine activation of STAT3 in MCF-7 cells ectopically expressing OSM-induced cellular scattering and peritumoral neovascularization of orthotopic xenografts. Conversely, selective inhibition of OSM by neutralizing antibody and Jak family kinases by tofacitinib inhibited STAT3 signaling, peritumoral angiogenesis, and cellular scattering. Importantly, nuclear staining of pSTAT3-Y705 identified at the tumor invasion front in ductal breast carcinomas correlates with increased lymphovascular invasion. Our work reveals the potential of novel therapeutic strategies targeting the OSM and STAT3 axis in patients with breast cancer harboring nuclear pSTAT3-Y705.
Metabolism of Fluorides
Authors: Harold C. Hodge
Journal: JAMA (1961)

FLUORIDE in small amounts unquestionably strengthens tooth defenses against dental caries. It cannot be listed literally as an element essential to life, but it is now established beyond reasonable doubt that optimal quantities of fluorides are desirable and beneficial in improving tooth health. When fluoride is naturally present in drinking water, is added mechanically, or more rarely, is ingested in more than minimal amounts in food, tooth decay diminishes. A knowledge of fluoride metabolism provides some understanding of the possible role of fluoride in tooth health, as well as some reassurance as to the safety of fluoridated water. Five aspects of the metabolic process will be discussed; absorption, distribution, excretion, deposition, and mobilization. No attention will be devoted to organic fluorides, such as carbon compounds containing fluorine. <h3>Absorption</h3> In fluoride metabolism, only the ion is important in the body. Compounds do not produce typical fluoride effects unless they release
Thyroid Hormone Levels and Recurrence of Major Depression
Authors: Russell T. Joffe, Michael Marriott
Journal: American Journal of Psychiatry (2000)

The relationship between basal thyroid hormone levels and acute antidepressant response has been studied, but any relationship between basal thyroid hormone levels and long-term course of depressive illness has not been evaluated.The authors used a Cox regression survival analysis to evaluate the relationship between life course of depressive illness and basal levels of thyroid hormones (triiodothyronine [T(3)], thyroxine [T(4)], and thyrotropin) in 75 outpatients with unipolar major depressive disorder.Time to recurrence of major depression was inversely related to T(3) levels but not to T(4) levels.These data may be of clinical interest in view of the fact that T(3) is used to augment antidepressant response.
Abstract 5275: Alternate mechanisms of PI3K pathway activation among subtypes of ductal carcinoma in situ suggest distinct pathways for progression to invasive disease
Authors: Rita Sakr, Sarat Chandarlapaty, Violetta Barbashina, Victor Andrade, Adriana Heguy, Mary Morrogh, Narciso Olvera, Wooyul Paik, Crispinita Arroyo, Monica Morrow, Neal Rosen, Tari King
Journal: Cancer Research (2010)

Abstract INTRODUCTION: Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway via kinase mutations or loss of PTEN is frequently reported in invasive breast cancer and laboratory models suggest that these “second hits” promote invasiveness in HER2 amplified disease. The role of PI3K pathway activation in the transition from in situ to invasive disease remains uncertain. The aim of this study was to assess the frequency of activating lesions in the PI3K pathway in pure high grade DCIS and DCIS associated with HER2 amplified invasive cancer. METHODS: 89 cases of pure high grade DCIS and 73 cases of DCIS associated with HER2 amplified (HER2+) invasive cancer were identified. Sections from FFPE blocks were used for IHC, FISH and DNA extraction. Pure DCIS, DCIS adjacent to invasive and matched invasive cancers were microdissected for multiplex array (Sequenom®) genotyping of PIK3CA and AKT. IHC was performed for HER2 and PTEN. HER2+ was confirmed by FISH. PTEN was scored relative to adjacent normal cells (scale 0-2). RESULTS: Among 89 cases of pure high grade DCIS, 51 (57%) were HER2+. PIK3CA mutations were identified in 13/73 (18%) HER2+ invasive lesions and in 11/13 cases the mutation was also present in the adjacent DCIS (11/73 (15%)). PIK3CA mutations were less common in pure HER2+ DCIS (2/51 (4%)) and pure HER2 neg DCIS (2/38 (5%)). Mutations in AKT1 were not identified HER2+ invasive lesions or the adjacent DCIS, yet were found in 3 cases of pure DCIS (2 HER2 neg, 1 HER2 +). PTEN loss was rare in HER2+ invasive lesions (4%), adjacent HER2+ DCIS (5%) and pure HER2+ DCIS (4%) but was seen in 7/38 (18%) cases of pure HER2 neg DCIS. Concomitant loss of PTEN and PIK3CA mutation was seen in 1 case of pure HER2 neg DCIS. CONCLUSIONS: PIK3CA mutations were observed with similar frequency in HER2+ invasive cancers and in the adjacent DCIS and were uncommon in pure DCIS, suggesting that mutational activation of PI3K may cooperate with HER2 in disease progression. PTEN loss was more common in HER2 neg DCIS and may not be mutually exclusive with PIK3CA mutations, suggesting that these mechanisms may interact in the progression of HER2 neg disease. AKT1 mutations were rare in pure DCIS and not identified in matched HER2+ DCIS and invasive cancer. These data support a role for activation of the PI3K pathway in the transition from in situ to invasive disease and suggest that the mechanism of activation may vary by HER2 status. Further work in HER2 neg DCIS and matched HER2 neg invasive cancer is underway. 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 5275.
Educating Physicians for Population-Based Clinical Practice
Authors: Merwyn R. Greenlick
Journal: JAMA (1992)

Debates about changing the current paradigm of medical education and medical practice have become fairly common in recent years. Based on my experience as a research director of a prepaid group practice program and as chair of a medical school department of public health and preventive medicine, I contend that the traditional one-to-one physician-patient role obligations should be expanded to include a set of "one-to-n" physician-population obligations. The latter include at least three components: (1) a resource allocation component, (2) a component focusing on the epidemiologic nature of clinical practice, and (3) a component focusing on members of the population who are not regularly attended to within the normal context of physician care. Discussing these in turn, I argue for a population-based clinical practice model of medical education that preserves the Hippocratic tradition while better preparing physicians for the complex practice and insurance realities of the 21st century. (<i>JAMA</i>. 1992;267:1645-1648)
Kallistatin Stimulates Vascular Smooth Muscle Cell Proliferation and Migration In Vitro and Neointima Formation in Balloon-Injured Rat Artery
Authors: Robert Q. Miao, Hideyuki Murakami, Qing Song, Lee Chao, Julie Chao
Journal: Circulation Research (2000)

Abstract —Kallistatin, a serine proteinase inhibitor (serpin), is expressed in the endothelial and smooth muscle cells of blood vessels. The potential function of kallistatin in vascular biology was investigated by studying its role in the proliferation and migration of cultured primary aortic vascular smooth muscle cells (VSMCs) in vitro and in neointima formation in rat artery after balloon angioplasty in vivo. Exogenous kallistatin induced a &gt;2-fold increase of VSMC proliferation and cell growth as measured by [ 3 H]thymidine incorporation and cell counts and a 2.3-fold increase of cell migration in modified Boyden chambers. In balloon-injured vessels, endogenous kallistatin mRNA and protein levels increased up to 10-fold as determined by competitive polymerase chain reaction and by ELISA. Intense staining of kallistatin mRNA was identified in the proliferating VSMCs of balloon-injured arteries during cell migration from media to neointima by in situ hybridization histochemistry and immunohistochemistry. We observed an induction of kallistatin expression by platelet-derived growth factor (PDGF) and upregulation of p42/44 mitogen-activated protein kinase (MAPK) activity by kallistatin in cultured VSMCs. Conversely, adenovirus-mediated transfer of kallistatin antisense cDNA into cultured VSMCs inhibited PDGF-induced p42/44 MAPK activity and cell proliferation. Furthermore, local delivery of adenovirus carrying kallistatin antisense cDNA significantly downregulated kallistatin mRNA levels and attenuated neointima formation in balloon-injured rat arteries in vivo. These results indicate that kallistatin may play an important role in mediating PDGF-induced MAPK pathway on VSMC proliferation and in neointima formation after balloon angioplasty.
Variation in Event Rates in Trials of Patients With Type 2 Diabetes
Authors: Bruce M. Psaty, Ross L. Prentice
Journal: JAMA (2009)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
The James D. Bruce Memorial Lecture on Preventive Medicine: Eradication of Poliomyelitis.
Authors: A. B. Sabin
Journal: Annals of Internal Medicine (1961)

s1 May 1961The James D. Bruce Memorial Lecture on Preventive Medicine: Eradication of Poliomyelitis.A. B. Sabin, M.D.A. B. Sabin, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1057_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe extensive field trials of 1959 on millions of susceptible persons of various ages not only established the safety and effectiveness of the oral, live poliovirus vaccine that I developed, but also suggested the possibility that the disease as well as the causative paralytic viruses could, under certain conditions, be completely eliminated. This is theoretically possible with the oral live vaccine, which gives rise to varying degrees of resistance to reinfection of the intestinal tract, but not with the killed virus vaccine, which, while protecting the individual against paralysis, does not prevent him from becoming a carrier.The first steps... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cincinnati, O. (CS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1961Volume 54, Issue 5Page: 1057-1057KeywordsParalysisPoliomyelitisPreventive medicineSafetyVaccines ePublished: 1 December 2008 Issue Published: 1 May 1961 PDF downloadLoading ...
Adeno-Associated Virus 2-Mediated Antiangiogenic Cancer Gene Therapy
Authors: Selvarangan Ponnazhagan, Gandham Mahendra, Sanjay Kumar, Denise R. Shaw, Cecil R. Stockard, William E. Grizzle, Sreelatha Meleth
Journal: Cancer Research (2004)

Abstract Angiogenesis is characteristic of solid tumor growth and a surrogate marker for metastasis in many human cancers. Inhibition of tumor angiogenesis using antiangiogenic drugs and gene transfer approaches has suggested the potential of this form of therapy in controlling tumor growth. However, for long-term tumor-free survival by antiangiogenic therapy, the factors controlling tumor neovasculature need to be systemically maintained at stable therapeutic levels. Here we show sustained expression of the antiangiogenic factors angiostatin and endostatin as secretory proteins by recombinant adeno-associated virus 2 (rAAV)-mediated gene transfer. Both vectors provided significant protective efficacy in a mouse tumor xenograft model. Stable transgene persistence and systemic levels of both angiostatin and endostatin were confirmed by in situ hybridization of the vector-injected tissues and by serum ELISA measurements, respectively. Whereas treatment with rAAV containing either endostatin or angiostatin alone resulted in moderate to significant protection, the combination of endostatin and angiostatin gene transfer from a single vector resulted in a complete protection. These data suggest that AAV-mediated long-term expression of both endostatin and angiostatin may have clinical utility against recurrence of cancers after primary therapies and may represent rational adjuvant therapies in combination with radiation or chemotherapy.
Chemokine and chemokine receptor expression during colony stimulating factor-1–induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for CCL9 (MIP-1γ) in osteoclastogenesis in vivo and in vitro
Authors: Meiheng Yang, Geneviève Mailhot, Carole A. MacKay, April Mason-Savas, Justin Aubin, Paul R. Odgren
Journal: Blood (2005)
Human monoclonal antibodies to group B streptococcus. Reactivity and in vivo protection against multiple serotypes.
Authors: H V Raff, P J Siscoe, E A Wolff, G Maloney, W Shuford
Journal: The Journal of Experimental Medicine (1988)

Group B streptococcal (GBS) infections cause significant mortality and morbidity among infants. Passive antibody immunotherapy has been proposed as treatment for infected infants. To this end, two human mAb-secreting cell lines were produced by EBV immortalization of human B cells. The mAbs were specific for the group B polysaccharide and bound to strains of all five serotypes as demonstrated by ELISA and crossed immunoelectrophoresis. The mAbs reacted and opsonized 100% (132/132) of the clinical isolates tested which represented all four capsule types. Both prophylactic and therapeutic protection with these mAbs were demonstrated in neonatal rats given lethal infections of types Ia and III human clinical isolates. These data indicate that a single human mAb directed against the group B carbohydrate can protect against GBS infections caused by the different serotypes. This antibody may be useful in the passive immunotherapy of infants infected with GBS.
Lifetime exposure to environmental lead and children's intelligence at 11-13 years: the Port Pirie cohort study
Authors: S. Tong, P. Baghurst, A. McMichael, M. Sawyer, J. Mudge
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To examine the association between environmental exposure to lead and children9s intelligence at age 11-13 years, and to assess the implications of exposure in the first seven years of life for later childhood development. <b>Design</b>: Prospective cohort study. <b>Subjects</b>: 375 children born in or around the lead smelting town of Port Pirie, Australia, between 1979 and 1982. <b>Main outcome measure</b>: Children9s intelligence quotient (IQ) measured at 11-13 years of age. <b>Results</b>: IQ was inversely associated with both antenatal and postnatal blood lead concentrations. Verbal, performance, and full scale IQ were inversely related to blood lead concentration with no apparent threshold. Multivariate analyses indicated that after adjustment for a wide range of confounders, the postnatal blood lead concentrations (particularly within the age range 15 months to 7 years) exhibited inverse associations with IQ. Strong associations with IQ were observed for lifetime average blood lead concentrations at various ages. The expected mean full scale IQ declined by 3.0 points (95% confidence interval 0.07 to 5.93) for an increase in lifetime average blood lead concentration from 0.48 to 0.96 µmol/l (10 to 20 µg/dl). <b>Conclusions</b>: Exposure to environmental lead during the first seven years of life is associated with cognitive deficits that seem to persist into later childhood. <h3>Key messages</h3> Few longitudinal data have yet been reported on the time course of the effects of exposure to environmental lead Exposure to environmental lead early in life is associated with cognitive deficits that persist into middle childhood The duration, intensity, and timing of exposure to lead, as well as other social and familial factors, may influence the nature and degree of reversibility The formulation of a public health policy for preventing any possible effects of lead exposure should be based on a composite consideration of the child9s health and the best use of existing resources
Unselective screening for liver disease may not be cost effective
Authors: M. Marks, A. Chadwick
Journal: BMJ (2014)

Sattar and colleagues review the epidemiology, manifestations, and management of non-alcoholic fatty liver disease.1 They recommend considering screening for other liver conditions such as chronic viral hepatitis, autoimmune liver disease, haemochromatosis, and drug induced liver injury. The value and cost implications of such screening in people with abnormal results in liver function tests are unclear.

A prospective …
A comparison of histocompatibility antigens in dermatitis herpetiformis and adult coeliac disease
Authors: P.P. SEAH, LIONEL FRY, J.W. KEARNEY, ELIZABETH CAMPBELL, J.F. MOWBRAY, J.S. STEWART, A.V. HOFFBRAND
Journal: British Journal of Dermatology (1976)

The incidence of histocompatibility antigens HL-A, 4a and 4b was studied in thirty-eight patients with dermatitis herpetiformis (DH) and thirty-six patients with adult coeliac disease (ACD). The 4b antigen was found in all the DH and ACD patients. HL-A 8 was found in 89% of patients with ACD similar to the incidence reported in previous studies—and in 79% of patients with DH, a higher incidence than in previous studies which may be due to stricter criteria being used here to diagnose DH. There was no significant difference in the incidence of HL-A 8 between those patients with DH whose small intestinal biopsies appeared macroscopically abnormal and those with a normal macroscopic appearance. These findings suggest that patients with DH form a single disease group and do not support the concept previously postulated that there are two groups of patients with DH, one with an increased incidence of HL-A 8 antigen similar to that in ACD who have a gluten sensitive enteropathy (GSE), and another with a normal incidence of HL-A 8 antigen and without enteropathy.
PRE-REPERFUSION METOPROLOL ADMINISTRATION DIMINISHES CMR-QUANTIFIED MICROVASCULAR OBSTRUCTION IN STEMI PATIENTS UNDERGOING PCI. ROLE OF NEUTROPHIL-PLATELET COAGGREGATES INHIBITION
Authors: Ines G. Lunar, Gonzalo Pizarro, Rodrigo Fernandez-Jimenez, Jaime García-Prieto, Esther Bernardo, Ana García-Alvarez, Leticia Fernandez-Friera, José Manuel García-Ruiz, Andres Iñiguez, Carlos Macaya Miguel, Valentin Fuster, Antonio Fernandez-Ortiz, Borja Ibanez
Journal: Journal of the American College of Cardiology (2014)
Nicholson "bitterly regrets" not meeting patient groups at Mid Staffs hospitals in 2009
Authors: G. Iacobucci
Journal: BMJ (2014)

The outgoing chief executive of NHS England, David Nicholson, has admitted that he “bitterly regrets” his failure to meet with patient groups during a visit to scandal hit Mid Staffordshire hospital trust in 2009, describing the decision as the “biggest mistake” of his eight year tenure in charge of the NHS.

Nicholson, who steps down at the end of this month, said he took the decision at the time in order to avoid a “media circus” like …
GMC under the cosh
Authors: R. Smith
Journal: BMJ (1998)

These are difficult times for the General Medical Council. The media seem to be circling, perhaps sensing a kill. The media are, of course, not one thing but a collection of newspapers, magazines, and radio and television programmes, most of them in furious competition. They do not ever sit down together and decide that something is a story, although they do feed off each other. Thus, when you see a pattern of stories about one organisation—like the GMC—it may mean that the media are reflecting some deeper social mood.

Sir Donald Irvine, the current president of the GMC, constantly reminds doctors that self regulation is not a right of professionals but rather a privilege that has to be earned every day. The media seem to be arguing that the medical profession is not keeping its side of the bargain—to guarantee that registered doctors are competent and trustworthy. And what the media say today, politicians may be forced to act on tomorrow, whether they want to or not. Few politicians want to pick a fight with the medical profession. Nor do they want to pick up the costs and headaches of regulating doctors, but there may come a point when …
TCT-149 Intracoronary injection of bone marrow derived mononuclear cells, early or late after acute myocardial infarction: Long-term effects on global left ventricular function - Twelve months MRI and long-term clinical results of the SWISS-AMI trial
Authors: Daniel Suerder, Robert Manka, Lucia Turchetto, Tiziano Moccetti, Paul Erne, Michel Zuber, Thomas F. Luescher, Stephan Windecker, Aris Moschovitis, Sebastian Kozerke, Roberto Corti
Journal: Journal of the American College of Cardiology (2014)