tbuckley/cabot-search huggingface dataset:
Transforming growth factor-β1 regulates macrophage migration via RhoA
Authors: Jun-Sub Kim, Jae-Gyu Kim, Mi-Young Moon, Chan-Young Jeon, Ha-Young Won, Hee-Jun Kim, Yee-Jin Jeon, Ji-Yeon Seo, Jong-Il Kim, Jaebong Kim, Jae-Yong Lee, Pyeung-Hyeun Kim, Jae-Bong Park
Journal: Blood (2006)
CONCERNING COMPENSATORY HYPERPLASIA OF THE INTIMA
Authors: Oskar Klotz
Journal: The Journal of Experimental Medicine (1910)

We agree with Jores and others that not one but many factors may be at work leading to intimal hyperplasia. Among these factors may be mentioned infection, bacterial toxins, organic poisons, inflammation and increased arterial tension. The theory of Thoma that the connective tissue developed in the intima is compensatory cannot be sustained. From the evidence which we have at hand it is not possible to state that the proliferative changes in the intima are uniformly secondary to the weakening of the media. Common influences may act simultaneously upon the media and the intima. Progressive medial degeneration of the peripheral arteries (Moenckeberg's sclerosis) is the result of muscle fatigue coupled with nutritional disturbance.
LEFT ATRIAL VOLUME INDEX (LAVI) OVER LATE DIASTOLIC MITRAL ANNULAR VELOCITY (A') IS A POWERFUL PREDICTOR OF CARDIAC DEATH AND CONGESTIVE HEART FAILURE (CHF) IN PATIENTS WITH A FIRST ST-ELEVATION ACUTE MYOCARDIAL INFARCTION (STEMI)
Authors: Noriaki Iwahashi, Masami Kosuge, Mitsuaki Endo, Nobuhiko Maejima, Kengo Tsukahara, Yoshio Tahara, Kiyoshi Hibi, Toshiaki Ebina, Shinichi Sumita, Satoshi Umemura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2011)
Abstract 2101: Role of CDK8 in estrogen receptor signaling in breast cancers
Authors: Martina McDermott, Balazs Gyorffy, Chang-uk Lim, Alexander Chumanevich, Zhengguan Yang, Mengqian Chen, James F. Catroppo, Igor Roninson, Eugenia V. Broude
Journal: Cancer Research (2014)

Abstract The majority of breast cancers (BrCa) overexpress estrogen receptor (ER)α, which regulates transcription and drives estrogen-stimulated proliferation of ER+ tumor cells. ER+ patients usually receive adjuvant anti-estrogen therapy based on ER modification, downregulation, or estrogen depletion. Tumors frequently develop resistance to anti-estrogen therapy through various mechanisms, which may involve stimulation of ER itself or of downstream mediators of ER-driven transcription, as well as activation of alternative proliferation pathways, in particular those driven by HER2/EGFR. The treatment efficacy of hormone-resistant BrCa could be greatly augmented by targeting new druggable mediators of ER activity. We have now identified a transcription-regulating oncogenic kinase CDK8 as a potentiator of ER signaling and ER-driven BrCa cell proliferation. Immunohistochemical staining of breast tissue arrays and bioinformatics analysis of gene expression microarray data of breast cancer patients revealed that CDK8 is overexpressed in BrCa and that higher CDK8 expression correlates with the failure of systemic therapy. Among systemically untreated patients, higher CDK8 expression was correlated with shorter relapse-free survival in a subset of ER+ tumors that expressed the lowest levels of ERα. This correlation suggested that CDK8 could play a role in the progression of ER+ breast cancers with reduced levels of ER, possibly by stimulating the mitogenic effects of ER-mediated transcription. Indeed, a selective small-molecule CDK8 inhibitor (Senexin A) decreased estrogen-induced ER-dependent transcription and inhibited estrogen-stimulated proliferation of ER+ BrCa cell lines. Microarray analysis revealed that CDK8 inhibition diminished the induction of genes that show rapid and sustained activation by estrogen in ER+ cells. CDK8 inhibition had an additive effect in combination with anti-estrogens in ER+ BrCa and a synergistic effect with fulvestrant in BrCa cells resistant to estrogen deprivation. Some of these cell lines also express HER2/EGFR, and CDK8 inhibition in combination with a HER2/EGFR inhibitor lapatinib synergistically inhibited the growth of these cells. These results suggest that combining anti-estrogen and anti-CDK8 therapy may be more effective than conventional hormone therapy for ER+ BrCa. Citation Format: Martina McDermott, Balazs Gyorffy, Chang-uk Lim, Alexander Chumanevich, Zhengguan Yang, Mengqian Chen, James F. Catroppo, Igor Roninson, Eugenia V. Broude. Role of CDK8 in estrogen receptor signaling in breast cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2101. doi:10.1158/1538-7445.AM2014-2101
THE FATE OF TYPHOID BACILLI WHEN INJECTED INTRAVENOUSLY INTO NORMAL RABBITS
Authors: Carroll G. Bull
Journal: The Journal of Experimental Medicine (1915)

Typhoid bacilli are agglutinated promptly in the circulating blood of normal rabbits and quickly removed from the blood stream. The clumped bacilli accumulate in the organs and are taken up by assembled polymorphonuclear leucocytes in the liver, spleen, and possibly other organs. The phagocyted clumps of bacilli are digested and destroyed by the phagocytes. Hence, destruction of typhoid bacilli intra vitam is brought about by an entirely different process than is the destruction by serum and whole blood in vitro. While the latter is caused by bacteriolysis, the former results from agglutination and intraphagocytic digestion. Lysis by fresh blood serum is not appreciably affected by spleen or kidney pulp, but it is inhibited by liver pulp. The action of the liver is referable to its biliary constituents, which exert anticomplementary action. Probably in certain examples of typhoid fever in man the typhoid bacilli in the circulating blood being inagglutinable cannot be removed by the organs and hence are not phagocyted and destroyed. The observed disparity between the ready destruction of typhoid bacilli by serum and shed blood and the resistance sometimes offered by the bacilli in the infected body is explained by the essential differences in the destructive processes in operation within and without the body.
Alexander Fleming: The Man and the Myth
Authors: Harold C. Neu
Journal: JAMA (1985)

Do we really need another book about Alexander Fleming? As a scientist who has devoted his last 15 years to working with β-lactam antibiotics and has read many of the works about Fleming, including the excellent writings of Ronald Hare, I questioned the need for a new book. Nevertheless, I was extremely pleased when I finished reading Dr Macfarlane's excellent account of Fleming. There has been so much controversy in recent years about Fleming's role in the development of penicillin that it is useful to have a text that fairly and honestly describes this famous man, born in a remote area of Scotland. The relationship of Fleming and Sir Almroth Wright is made much clearer by Macfarlane than in any of the early works about Fleming. Fleming's earlier works on antiseptics and their deleterious effect on wounds may have been one of the reasons that he was slow to pursue
Benefit of the 70-gene profile for widely used guidelines: an answer to increased selection for adjuvant chemotherapy in breast cancer.
Authors: M Knauer, V Retèl, J Bueno-de-Mesquita, E Rutgers, W van Harten, S Rodenhuis, M van de Vijver, L van 't Veer, S Linn
Journal: Cancer Research (2009)

Abstract Abstract #1084 Introduction:&amp;#x2028; Risk assessment for breast cancer patients differs substantially among treatment guidelines. The NCCN, St.Gallen, Adjuvant!Online, and Dutch 2008 guidelines are less restrictive in comparison to the 2004 Dutch guidelines and Nottingham Prognostic Index, when selecting patients for adjuvant systemic treatment. The Dutch Institute for Healthcare Improvement (CBO) has introduced slight changes in the concept 2008 guidelines. Adjuvant systemic treatment is only advised when the absolute 10-years survival benefit is 5% or more. The new recommendations for adjuvant systemic treatment are based on survival tables used in the Adjuvant! software. The changes affect only node-negative patients aged 35 years: since 2008 patients with G2/G3 tumors &amp;gt;1cm or every tumor &amp;gt;2cm are advised to undergo adjuvant systemic therapy, while in 2004 this was the case for tumors G3&amp;gt;1cm, G2&amp;gt;2cm or every tumor &amp;gt;3cm.&amp;#x2028; Patients and Methods:&amp;#x2028; Risk was assessed for 427 lymph-node negative (LNN) patients in the prospective RASTER-study (Bueno-de-Mesquita, 2007) and 151 LNN patients in the NEJM-series (van de Vijver, 2002). Clinical risk was calculated using the 2004 and 2008 Dutch guidelines. Genetic risk was assigned according to the result of the Amsterdam 70-gene signature. Survival analyses were done according to the univariate Kaplan-Meier-method.&amp;#x2028; Results:&amp;#x2028; Instead of 57% in 2004, in 2008 only 24% of patients were assigned to clinical low risk in the RASTER study, and 141 patients (33%) changed from low to high risk (p&amp;lt;0.001). The rate of discordant findings between clinical assessment and 70-gene signature increased from 30% in 2004 to 41% in 2008 (p&amp;lt;0.001, table 1). Similar results were obtained for the 151 patients of the NEJM-series (30% and 35% discordance for the 2004 and 2008 CBO guidelines, respectively). At 10 years follow-up, differences between the high and low risk categories according to the 2004, 2008 guidelines and the 70-gene profile, were best predicted by the latter: distant-disease-free survival (DDFS) log-rank p=0.002, p=0.11 and p&amp;lt;0.001 respectively.&amp;#x2028; &amp;#x2028; Conclusion:&amp;#x2028; As adjuvant systemic treatments become more effective, guidelines become less restrictive, resulting in more patients being selected for adjuvant therapy. Since newer treatment guidelines do not better predict survival, the magnitude of the 70-gene profiles benefit, which is defined as proportion of patients in whom over- and undertreatment can be avoided, depends on present guidelines for risk assessment and shows a remarkable increase. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1084.
WHO team visits Israel to learn about adult circumcision
Authors: Judy Siegel-Itzkovich
Journal: BMJ (2006)

The World Health Organization has sent a team of AIDS experts to Israel to gather information on circumcision of adult men that developing countries can use. These countries are interested in expanding the practice to try to reduce the rate of transmission of HIV. 

Tim Farley, of WHO's department of reproductive health and research, and Timothy Hargreaves, a WHO consultant from the University of Edinburgh, viewed the ritual circumcision in a Jerusalem hospital of a 21 year old Jewish immigrant from Russia who had not been circumcised as a baby. 

Israel has much experience of circumcision …
Michael Ernest Nicholas Anfilogoff
Authors: R. Anfilogoff
Journal: BMJ (2009)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Michael Ernest Nicholas Anfilogoff Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Serum Brain-Derived Neurotrophic Factor as a Predictor of Incident Dementia
Authors: Kenji Hashimoto
Journal: JAMA Neurology (2014)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
Telomeres, stem cells, senescence, and cancer
Authors: Norman E. Sharpless, Ronald A. DePinho
Journal: Journal of Clinical Investigation (2004)

Mammalian aging occurs in part because of a decline in the restorative capacity of tissue stem cells. These self-renewing cells are rendered malignant by a small number of oncogenic mutations, and overlapping tumor suppressor mechanisms (e.g., p16INK4a-Rb, ARF-p53, and the telomere) have evolved to ward against this possibility. These beneficial antitumor pathways, however, appear also to limit the stem cell life span, thereby contributing to aging.
The lysosomal-mitochondrial axis in free fatty acid-induced hepatic lipotoxicity
Authors: ZhengZheng Li, Michael Berk, Thomas M. McIntyre, Gregory J. Gores, Ariel E. Feldstein
Journal: Hepatology (2008)

Impaired mitochondrial function is largely thought to be a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms resulting in mitochondrial dysfunction in NAFLD remain poorly understood. This study examined the effects of excessive accumulation of free fatty acids (FFAs) in liver cells on mitochondrial function and the role of the lysosomal-mitochondrial axis on lipotoxicity. Primary mouse hepatocytes, HepG2 and McNtcp.24 cells, were treated with varied concentrations of FFAs with different degrees of saturation for up to 24 hours. Mitochondrial function was monitored by real-time imaging, cytochrome c redistribution, and reactive oxygen species (ROS) production. The temporal relationship of lysosomal and mitochondrial permeabilization was established. Activity of the lysosomal protease cathepsin B was suppressed by genetic and pharmacological approaches. Cathepsin B–knockout mice and wild-type animals were place on a high-carbohydrate diet for 16 weeks, and mitochondrial function and liver damage were assessed. Exposure of liver cells to saturated FFAs resulted in mitochondrial depolarization, cytochrome c release, and increased ROS production. Lysosomal permeabilization and cathepsin B redistribution into the cytoplasm occurred several hours prior to mitochondrial dysfunction. Either pharmacological or genetic inhibition of cathepsin B preserved mitochondrial function. Finally, cathepsin B inactivation protected mitochondria, decreased oxidative stress, and attenuated hepatic injury in vivo. Conclusion: These data strongly suggest excessive accumulation of saturated FFAs in liver cells directly induce mitochondrial dysfunction and oxidative stress. Our data further suggest this process is dependent on lysosomal disruption and activation of cathepsin B.
Outcome of work-related asthma exacerbations in Quebec and Ontario
Authors: Catherine Lemière, Teresa To, Carlo de Olim, Marcos Ribeiro, Gary Liss, M. Diane Lougheed, Ryan Hoy, Amélie Forget, Lucie Blais, Jingqin Zhu, Susan M. Tarlo
Journal: European Respiratory Journal (2014)

There are differences in the management of workers with work-related asthma within Canadian provinces. In Quebec, the compensation of a case of occupational asthma is usually based on the positivity of a specific inhalation challenge, whereas in Ontario, the diagnosis is usually based on serial peak expiratory flow (PEF), provocative methacholine concentration causing a 20% decrease in forced expiratory volume in 1 s (PC20) monitoring at and away from work, and specific skin-prick tests (that is, less often on specific inhalation challenges) [1]. We aimed: 1) to compare the delay between the onset of work-related asthma symptoms and the diagnosis of occupational asthma and work-exacerbated asthma between Quebec and Ontario; and 2) to assess and compare the healthcare utilisation in subjects with occupational asthma and work-exacerbated asthma between the provinces before and after the first assessment in two tertiary clinics in Quebec and Ontario that specialise in work-related asthma. Diagnosing work-related asthma decreased asthma-related healthcare utilisation in Quebec and Ontario <http://ow.ly/CFrPk> Provincial population-based administrative data were made available for record linkage of the study populations. In Ontario, record linkage was conducted by the Institute for Clinical Evaluative Sciences and in Quebec, the Régie de l'assurance maladie du Québec. The opinions, results, and conclusions reported in this paper are those of the authors and are independent of these agencies: The authors want to thank Suzanne Dostaler for her administrative support of the AllerGen NCE grant.
ST. HELENIAN CELLULITIS.
Authors: I.B. SHINE
Journal: British Journal of Dermatology (1964)

Journal Article ST. HELENIAN CELLULITIS. Get access I.B. SHINE I.B. SHINE Population Genetics Research Unit, Old Road, Headington, Oxford Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 76, Issue 8-9, 1 August 1964, Pages 357–361, https://doi.org/10.1111/j.1365-2133.1964.tb14542.x Published: 01 August 1964
A long‐term study of hemophilic arthropathy of the knee joint on a program of factor VIII replacement given at time of each hemarthrosis
Authors: Doreen B. Brettler, Ann D. Forsberg, Francis D. O'Connell, Andrew I. Cederbaum, Andrea K. Chaitman, Peter H. Levine
Journal: American Journal of Hematology (1985)

Because there is little available data to demonstrate whether demand therapy is adequate to prevent progression of hemophilic arthropathy, a cohort of 64 patients with severe Hemophilia A (Factor VIII level less than 1%) and no inhibitor were studied with respect to the progression of knee arthropathy over a period of 6 years. Both degree of disease in flexion and extension and progression of disease were rated on an arbitrary scale. At the outset of the study, the majority of knees were either not restricted or mildly restricted as to motion. Of those knees that were not restricted at the outset, 96% remained not restricted. Of the knees that were mildly restricted, only 58% remained stable or improved over the 6 years, and of the knees that were moderately to severely restricted, 75% improved or remained stable. It thus appears that a demand therapy program can maintain normal range of motion in a knee joint. However, if the patient's joint has progressed to mild disease, the ability to maintain or improve the joint with demand therapy appears to be decreased.
Adaptive Dose-Finding Studies: A Review of Model-Guided Phase I Clinical Trials
Authors: Alexia Iasonos, John O'Quigley
Journal: Journal of Clinical Oncology (2014)

Purpose We provide a comprehensive review of adaptive phase I clinical trials in oncology that used a statistical model to guide dose escalation to identify the maximum-tolerated dose (MTD). We describe the clinical setting, practical implications, and safety of such applications, with the aim of understanding how these designs work in practice. Methods We identified 53 phase I trials published between January 2003 and September 2013 that used the continual reassessment method (CRM), CRM using escalation with overdose control, or time-to-event CRM for late-onset toxicities. Study characteristics, design parameters, dose-limiting toxicity (DLT) definition, DLT rate, patient-dose allocation, overdose, underdose, sample size, and trial duration were abstracted from each study. In addition, we examined all studies in terms of safety, and we outlined the reasons why escalations occur and under what circumstances. Results On average, trials accrued 25 to 35 patients over a 2-year period and tested five dose levels. The average DLT rate was 18%, which is lower than in previous reports, whereas all levels above the MTD had an average DLT rate of 36%. On average, 39% of patients were treated at the MTD, and 74% were treated at either the MTD or an adjacent level (one level above or below). Conclusion This review of completed phase I studies confirms the safety and generalizability of model-guided, adaptive dose-escalation designs, and it provides an approach for using, interpreting, and understanding such designs to guide dose escalation in phase I trials.
Tobacco Support Programs
Authors: Horace R. Kornegay
Journal: JAMA (1975)

To the Editor.—  Last Dec 16,The Journalpublished an article (230: 1529, 1974) and an editorial (230: 1564, 1974) that called on Congress to abolish the tobacco support programs. WhileThe Journalhas the same privilege as any other publication in this country to make recommendations for legislation, it has at the same time a responsibility to adhere to facts. Because in our viewThe Journal'sarguments were not factually accurate, the following observations are pertinent.  The Journalreported that a decline in US heart disease death rates began with cessation of smoking after what it called the watershed 1964 report of the Advisory Committee to the Surgeon General, Smoking and Health . This observation apparently resulted from a misunderstanding of the data. The problem was compounded by a misconception of the effects of government tobacco programs.  Footnotes indicated reliance on two government publications. 1,2 The Table of this
Dickinson W. Richards Lecture: Circulatory adjustments to hypoxia.
Authors: D D Heistad, F M Abboud
Journal: Circulation (1980)

Circulatory adjustments during hypoxia act to redistribute blood flow and maintain arterial pressure. Redistribution of blood flow is accomplished by a local effect of hypoxia, which produces dilatation in coronary and cerebral vessels, and the chemoreceptor reflex, which produces vasoconstriction in skeletal muscle and the splanchnic bed and dilatation in coronary vessels. Arterial pressure is maintained primarily by the chemoreceptor reflex. If the chemoreceptor reflex fails to maintain arterial pressure, hypoxia and hypotension together activate the central pressor response. Compensatory mechanisms usually are sufficient to maintain homeostasis during hypoxia. However, when a hypotensive stress is superimposed during hypoxia, compensatory mechanisms may fail to maintain arterial pressure. Thus, systemic hypoxia interferes with autonomic cardiovascular adjustments.