tbuckley/cabot-search huggingface dataset:
AllergoOncology: the role of IgE‐mediated allergy in cancer
Authors: E. Jensen‐Jarolim, G. Achatz, M. C. Turner, S. Karagiannis, F. Legrand, M. Capron, M. L. Penichet, J. A. Rodríguez, A. G. Siccardi, L. Vangelista, A. B. Riemer, H. Gould
Journal: Allergy (2008)

Epidemiological studies have suggested inverse associations between allergic diseases and malignancies. As a proof of concept for the capability of immunoglobulin E (IgE) to destruct tumor cells, several experimental strategies have evolved to specifically target this antibody class towards relevant tumor antigens. It could be demonstrated that IgE antibodies specific to overexpressed tumor antigens have been superior to any other immunoglobulin class with respect to antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) reactions. In an alternative approach, IgE nonspecifically attached to tumor cells proved to be a powerful adjuvant establishing tumor-specific immune memory. Active Th2 immunity could also be achieved by applying an oral immunization regimen using mimotopes, i.e. epitope mimics of tumor antigens. The induced IgE antibodies could be cross-linked by live tumor cells leading to tumoricidic mediator release. Thus, IgE antibodies may not only act in natural tumor surveillance, but could possibly also be exploited for tumor control in active and passive immunotherapy settings. Thereby, eosinophils, mast cells and macrophages can be armed with the cytophilic IgE and become potent anti-tumor effectors, able to trace viable tumor cells in the tissues. It is strongly suggested that the evolving new field AllergoOncology will give new insights into the role of IgE-mediated allergy in malignancies, possibly opening new avenues for tumor therapy.
RU-486-Reply
Authors: Etienne-Emile Baulieu
Journal: JAMA (1990)

<h3>In Reply.—</h3> Mr Godefroid implies that the subject of RU-486 in fertility control should be excluded from open consideration, in reputable journals, by physicians. This notion belongs to a class of argument that, if given a bit of thought, needs no further discussion. Moreover, the language used by Mr Godefroid is designed, through thoroughly unscientific semantic manipulation, to bring about a rejection a priori of the facts I present and the ideas I wish to communicate to the medical community. As all know, great care must be taken in extracting phrases from their contexts. The fact remains that thousands of women die each year and millions are wounded and traumatized by poorly performed abortions, legal or illegal. Is it not precisely our obligation as physicians, working for life and health, to consider seriously every and any solution to such a high death rate? Although the definition of "personhood" is not
Experimental Therapy of Hepatoma with Artemisinin and Its Derivatives: <i>In vitro</i> and <i>In vivo</i> Activity, Chemosensitization, and Mechanisms of Action
Authors: Junmei Hou, Disong Wang, Ruiwen Zhang, Hui Wang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: ART and its derivatives, clinically used antimalarial agents, have recently shown antitumor activities. However, the mechanisms underlying these activities remain unclear. This study was designed to determine their antitumor efficacy and underlying mechanisms of action in human hepatoma cells. Experimental Design: The in vitro cytotoxicities of ART, DHA, artemether, and artesunate were compared in human hepatoma cells, HepG2 (p53 wild-type), Huh-7 and BEL-7404 (p53 mutant), and Hep3B (p53 null), and a normal human liver cell line, 7702. Based on their activity and specificity, ART and DHA were further investigated for their in vitro and in vivo antitumor effects and their effects on the protein expression of genes associated with cell proliferation and apoptosis. Results: ART and DHA exerted the greatest cytotoxicity to hepatoma cells but significantly lower cytotoxicity to normal liver cells. The compounds inhibited cell proliferation, induced G1-phase arrest, decreased the levels of cyclin D1, cyclin E, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and E2F1, and increased the levels of Cip1/p21 and Kip1/p27. They induced apoptosis, activated caspase-3, increased the Bax/Bcl-2 ratio and poly(ADP-ribose) polymerase, and down-regulated MDM2. In mice bearing HepG2 and Hep3B xenograft tumors, ART and DHA inhibited tumor growth and modulated tumor gene expression consistent with in vitro observations. DHA increased the efficacy of the chemotherapeutic agent gemcitabine. Conclusions: ART and DHA have significant anticancer effects against human hepatoma cells, regardless of p53 status, with minimal effects on normal cells, indicating that they are promising therapeutics for human hepatoma used alone or in combination with other therapies.
Environmental factors contributing to the development of childhood leukemia in children with Down's syndrome
Authors: J M Mejía-Aranguré, A Fajardo-Gutiérrez, H Flores-Aguilar, M C Martínez-García, F Salamanca-Gómez, V Palma-Padilla, R Paredes-Aguilera, R Bernáldez-Ríos, A Ortiz-Fernández, A Martínez-Avalos, C Gorodezky
Journal: Leukemia (2003)
Coincidence of Gaucher's disease due to a private mutation and Ph′ positive chronic myeloid leukemia
Authors: Petro E. Petrides, Philipp leCoutre, Johann Müller-Höcker, Eberhard Magin, Klaus Harzer, Anna Demina, Ernest Beutler
Journal: American Journal of Hematology (1998)

We report the case of a 46-year-old female with coexisting type I Gaucher's disease and chronic myeloid leukemia (CML). The diagnosis of Gaucher's disease was made in early childhood by bone marrow biopsy and was recently confirmed by biochemical demonstration of reduced leukocyte β-glucocerebrosidase activity and the presence of Gaucher cells in a bone marrow aspirate. We analyzed the patient's genomic DNA for the underlying glucocerebrosidase mutations and have found homozygosity for a C→T transition in cDNA nucleotide 593 (159 Pro→Leu), presently an undescribed mutation. After initiation of replacement therapy with alglucerase we observed a significant increase of the platelet count in our patient. The diagnosis of CML was based on standard hematological parameters and the detection of the Philadelphia chromosome (Ph). With intermittent treatment with busulfan the patient has remained in chronic phase for nine years. The patient suffered from hepatosplenomegaly and thrombocytopenia, both of which can be caused by Gaucher's disease and CML. The aggravation of skeletal manifestations of Gaucher's disease, which occurred at the time of diagnosis of CML, could be due to increased production of leukocyte-derived glucocerebrosides that were not appropriately degraded because of the genetic β-glucocerebrosidase deficiency. Am. J. Hematol. 59:87–90, 1998. © 1998 Wiley-Liss, Inc.
Hall of Mirrors
Authors: Lester S. King
Journal: JAMA (1966)

Of the many novels written about doctors, only relatively few have been written by doctors, and of these only a small number have high literary merit. Hall of Mirrors belongs to this latter category.  The interest lies on two planes. The subtitle Doctors on Trial refers first of all to the antagonists engaged in a libel suit. But the trial also refers to the medical profession as a whole, which comes under significant implied criticism. The plot—thoroughly absorbing and maintaining its suspense to the very end—concerns a libel action which followed the death of a prominent political figure. The illness had been misdiagnosed. A surgeon, deeply involved with computer technique, alleged that had the physician in charge used an available computer (the novel takes place in the future) this might have provided a diagnosis. There was the insinuation that, considering the puzzling features of the case, failure to use such
Pirfenidone Prevents the Development of a Vulnerable Substrate for Atrial Fibrillation in a Canine Model of Heart Failure
Authors: Ken W. Lee, Thomas H. Everett, Dulkon Rahmutula, Jose M. Guerra, Emily Wilson, Chunhua Ding, Jeffrey E. Olgin
Journal: Circulation (2006)

Background— Atrial fibrosis is an important substrate in atrial fibrillation (AF), particularly in the setting of structural heart disease. In a canine model, congestive heart failure (CHF) produces significant atrial fibrosis and the substrate for sustained AF. This atrial remodeling is a potential therapeutic target. The objective of the present study is to evaluate the effects of the antifibrotic drug pirfenidone (PFD) on arrhythmogenic atrial remodeling in a canine CHF model. Methods and Results— We studied 15 canines, divided equally into 3 groups: control, CHF canines not treated with PFD, and CHF canines treated with PFD. CHF was induced by ventricular tachypacing (220 bpm for 3 weeks), and oral PFD was administered for the 3-week pacing period. We performed electrophysiology and AF vulnerability studies, atrial fibrosis measurements, and atrial cytokine expression studies. Only canines in the untreated CHF group developed sustained AF (&gt;30 minutes, 4 of 5 canines; P &lt;0.05). Treatment of CHF canines with PFD resulted in an attenuation of arrhythmogenic left atrial remodeling, with a significant reduction in left atrial conduction heterogeneity index (median [25% to 75% interquartile range] 4.96 [3.53 to 5.64] versus 2.52 [2.11 to 2.82], P &lt;0.01; pacing cycle length 300 ms), left atrial fibrosis (16.0% [13.0% to 17.5%] versus 8.7% [5.7% to 10.6%], P &lt;0.01), and AF duration (1800 [1020 to 1800] seconds versus 6 [5 to 22] seconds, P &lt;0.01). Immunoblotting studies demonstrated the drug’s effects on multiple cytokines, including a reduction in transforming growth factor-β1 expression. Conclusions— Treatment of CHF canines with PFD results in significantly reduced arrhythmogenic atrial remodeling and AF vulnerability. Pharmacological therapy targeted at the fibrotic substrate itself may play an important role in the management of AF.
Control, Complications, Confidence: The Regenstrief Conference on the Risks and Benefits of Intensive Management in NIDDM
Authors: Frank Davidoff
Journal: Annals of Internal Medicine (1996)

Editorials1 January 1996Control, Complications, Confidence: The Regenstrief Conference on the Risks and Benefits of Intensive Management in NIDDMFrank Davidoff, MD, EditorFrank Davidoff, MD, EditorSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-1_Part_1-199601010-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Many adult diabetic patients and their doctors, it seems, minimize the importance of non-insulin dependent diabetes mellitus (NIDDM), seeing it as “just a touch of sugar” and not confronting the real damage it can inflict. But even those of us who, as diabetologists, have spent a good part of our careers struggling with the worst diabetes has to offer—the ugly foot ulcers and the mutilating amputations, the enervating nephrotic syndrome and renal failure, the seemingly endless constipation and diarrhea and gastroparesis, the ravages of galloping proliferative retinopathy—have until now directed our therapies more to the control of acute, present symptoms ...References1. Davidoff F, Case K, Fried P. Evidence-based medicine: why all the fuss? [editorial] Ann Intern Med. 1996; 122:727. Google Scholar2. McDonald C. Medical heuristics: the silent adjudicators of practice patterns. Ann Intern Med. 1996; 124 (1 pt 1):56-62. Google Scholar3. Diamond G, Forrester JS. Metadiagnosis. An epistemologic model of clinical judgment. Am J Med. 1983; 75:129-37. Google Scholar4. Thornton JG, Lilford RJ, Johnson N. Decision analysis in medicine. BMJ. 1992; 304:1099-103. Google Scholar5. Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non–insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Research and Clinical Practices. 1995; 28:103-17. Google Scholar Author, Article, and Disclosure InformationAuthors: Frank Davidoff, MD, Editor PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMoving Diabetes Care from Science to Practice: The Evolution of the National Diabetes Prevention and Control ProgramDara Murphy, MPH, Tom Chapel, MA, MBA, and Cynthia Clark, MAChallenges in the dietary treatment of cystic fibrosis related diabetes mellitusDIABETES MELLITUS IN OLDER PERSONS 1 January 1996Volume 124, Issue 1_Part_1Page: 65-66KeywordsDiabetes mellitusExtrapolationForecastingHealth careHypertensionInsulinTouchToxicityType 2 diabetesUlcers ePublished: 15 August 2000 Issue Published: 1 January 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The magic number and the episodic buffer
Authors: Alan Baddeley
Journal: Behavioral and Brain Sciences (2001)

Cowan's revisiting of the magic number is very timely and the case he makes for a more moderate number than seven is persuasive. It is also appropriate to frame his case within a theoretical context, since this will influence what evidence to include and how to interpret it. He presents his model however, as a contrast to the working memory model of Baddeley (1986). I suggest that this reflects a misinterpretation of our model resulting in a danger of focusing attention on pseudo-problems rather than genuine disparities between his approach and my own.
The development of immunomodulatory monoclonal antibodies as a new therapeutic modality for cancer: The Bristol-Myers Squibb experience
Authors: David Berman, Alan Korman, Ronald Peck, David Feltquate, Nils Lonberg, Renzo Canetta
Journal: Pharmacology & Therapeutics (2014)

The discovery and increased understanding of the complex interactions regulating the immune system have contributed to the pharmacologic activation of antitumor immunity. The activity of effector cells, such as T and NK cells, is regulated by an array of activating and attenuating receptors and ligands. Agents that target these molecules can modulate immune responses by exerting antagonistic or agonistic effects. Several T- or NK-cell modulators have entered clinical trials, and two have been approved for use. Ipilimumab (Yervoy®, Bristol-Myers Squibb) and nivolumab (OPDIVO, Ono Pharmaceutical Co., Ltd./Bristol-Myers Squibb) were approved for the treatment of metastatic melanoma, in March 2011 in the United States, and in July 2014 in Japan, respectively. The clinical activity of these two antibodies has not been limited to tumor types considered sensitive to immunotherapy, and promising activity has been reported in other solid and hematologic tumors. Clinical development of ipilimumab and nivolumab has presented unique challenges in terms of safety and efficacy, requiring the establishment of new evaluation criteria for adverse events and antitumor effects. Guidelines intended to help oncologists properly manage treatment in view of these non-traditional features have been implemented. The introduction of this new modality of cancer treatment, which is meant to integrate with or replace the current standards of care, requires additional efforts in terms of optimization of treatment administration, identification of biomarkers and application of new clinical trial designs. The availability of immune modulators with different mechanisms of action offers the opportunity to establish immunological combinations as new standards of care.
Inorganic Nanoparticles Based Contrast Agents for X‐ray Computed Tomography
Authors: Anshuman Jakhmola, Nicolas Anton, Thierry F. Vandamme
Journal: Advanced Healthcare Materials (2012)

Abstract Nanomaterials have gained considerable attention and interest in the development of new and efficient molecular probes for medical diagnosis and imaging. Heavy metal nanoparticles as such are excellent absorber of X‐rays and can offer excellent improvement in medical diagnosis and X‐ray imaging. Substantial progress has been made in the synthesis protocol and characterization studies of these materials but a major challenge still lies in the toxicological studies, which are rather incomplete. The worst known cases were those associated with Thorotrast (suspension of ThO 2 nanoparticles) which resulted in many deaths over years. Properly protected nanomaterials conjugated or coated with biocompatible materials can be used for the fabrication of various functional systems with multimodality, targeting properties, reduced toxicity and proper removal from the body. This review aims mainly to provide the advances in the development of inorganic nanoparticle based X‐ray contrasting agents with an overview of methods of their preparation, functionalization and applications in medical diagnosis.
BCG: An Effective Immunizing Agent
Authors: William R. Barclay
Journal: JAMA (1983)

BCG, an attenuated strain of<i>Mycobacterium tuberculosis</i>, has been used as a vaccine against tuberculosis for more than 50 years. There is no consensus, however, on the degree of protection it may offer. Antibacterial vaccines, unlike antiviral vaccines, usually produce only relative protection. Therefore, they offer little hope of eradicating a disease, and their usefulness must be judged by the amount of protection conferred<i>v</i>the cost of administration, and the overall resources that exist to limit the spread of a disease must also be considered. As pointed out by Clemens et al in this issue ofThe Journal(p 2362), BCG vaccine trials have shown a broad spectrum of effectiveness, all the way from increasing susceptibility to tuberculosis to 80% protection. The eight trials analyzed in this study represent only a small percentage of those that have been conducted throughout the world, but they are the ones that best
Abstract 4162: PTPRO silencing by MAPK pathway in colorectal cancer
Authors: Loredana Vecchione, Antonio Fabio di Narzo, Layka Abbasi Asbagh, Sabine Tejpar
Journal: Cancer Research (2012)

Abstract Background The analysis of gene expression profile of a total of 688 primary colorectal (CRC) cancers revealed PTPRO to have an intriguing bimodal distribution. When looking for variables associated to it, such as clinical variables, mutation status, gene copy number variation and methylation pattern, a significant association was found with the BRAF mutated (BRAF mut) tumors and a not perfect association with the CIMP high methylation subtype. Based on these findings, we postulated that the Ras/Raf mitogen activated protein kinase (MAPK) pathway and the methylation could concomitantly or independently be involved in the downregulation of the gene. Material and methods Basal PTPRO mRNA was evaluated in a total of 13 CRC cell lines (7 wild type for BRAF and KRAS, 2 BRAF mut and 4 KRAS mut) by RT-qPCR. PTPRO promoter region (366bp, 15475534 - 15475900 - Human Genome browser gateway NCBI36/hg18) was studied by sequencing analysis after bisulfite conversion of DNA extracted from these cells. Treatments with 10 microM of 5-azacytidine (5-AZA), 1 microM of Mek inhibitor (AS703026) and the combination of 10 microM of 5-AZA with 1 microM of Meki were performed in SW480 and Lim1215. After 72 hrs of treatment samples were profiled for gene expression and methylation. Results 10 out of 13 cell lines showed low PTPRO expression at mRNA level independently from the methylation status. The expression of the gene was induced after treatment with 5-AZA in SW480 and Lim1215. PTPRO expression was also induced after Mek inhibition of 5,6 fold and 44 fold in SW480 and Lim1215, respectively, without any modifications of the methylation pattern. Moreover, Mek inhibitor could further increase the expression of the gene in cells treated with 5-AZA Conclusion Our clinical and preclinical data confirm the MAPK pathway to be involved in PTPRO silencing independently from its methylation status. PTPRO loss might play a role in mediating the oncogenic function of the MAPK activation in CRC cells either by deregulating receptor type kinanses (RTKs) or by directly modulating Erk activity. On going experiments will answer to this question Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4162. doi:1538-7445.AM2012-4162
Cross-Sectional Study of Older Outpatients With Schizophrenia and Healthy Comparison Subjects: No Differences in Age-Related Cognitive Decline
Authors: Lisa T. Eyler Zorrilla, Robert K. Heaton, Lou Ann McAdams, Sidney Zisook, M. Jackuelyn Harris, Dilip V. Jeste
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Little is known about the progression of cognitive deficits in older, community-dwelling patients with schizophrenia, especially in comparison to healthy subjects. METHOD: The authors examined the relationship of age to performance on the Mattis Dementia Rating Scale in 116 outpatients with schizophrenia and 122 normal comparison subjects. Subjects ranged in age from 40 to 85 years. RESULTS: Dementia Rating Scale scores were lower in the schizophrenia group but correlated negatively with age in both groups, with no significant differences seen between the schizophrenia and normal comparison groups in slopes that depicted age-related variation. CONCLUSIONS: This cross-sectional study suggests a relatively stable long-term course of cognitive impairment in individuals with schizophrenia, with no evidence of faster cognitive decline in outpatients with schizophrenia than in normal comparison subjects.
Studies of the Arterial Pulse Wave
Authors: ARTHUR W. FEINBERG, HENRY LAX, William Urban
Journal: Circulation (1958)

Previous studies have shown abnormalities of the arterial pulse wave in hypertensive subjects of all age groups. The major change has been diminution to disappearance of the dicrotic wave. The pharmacologic differences between epinephrine and norepinephrine offer a means of studying the mechanism of this change in the dicrotic wave. In the present study, normotensive subjects have had transient hypertension induced by the infusion of epinephrine and norepinephrine. The different effects of these drugs on their arterial pulse waves have been recorded.
Computerized Surveillance of Diabetic Patient/Health Care Delivery System Interfaces
Authors: Douglas Bryant, Allene Van Son, Paul J Davis, Carol Segal
Journal: Diabetes Care (1978)

DIASURV is a computerized surveillance program developed to monitor the interaction of a large cohort of diabetic patients with a tertiary care institution. The input of this simple program consists of a file of diabetic patients, the daily census of hospital inpatients, and the daily census of hospital outpatients. Written in COBOL, the program consists of edit and file-maintenance components and inpatient and outpatient search components. The output is a daily listing of all inpatient (x- = 60) and outpatient transactions (x- = 20) for the cohort of 1,800 patients. The output also summarizes previous exposures of patients to specific bedside and classroom activities in diabetes education. DIASURV has a variety of applications in terms of organization of teaching efforts and facilitated access to a limited amount of patient management information.