tbuckley/cabot-search huggingface dataset:
Abstract 4922: <i>KRAS</i> and <i>BRAF</i> mutations influence correlation structure of locus-specific CpG island methylation and CIMP in colorectal cancer
Authors: Shuji Ogino, Noriko Tanaka, Katsuhiko Nosho, Curtis Huttenhower, John Quackenbush, Kevin Haigis, Charles Fuchs
Journal: Cancer Research (2010)

Abstract Background: The CpG island methylator phenotype (CIMP-high or CIMP1) is a distinct phenotype associated with microsatellite instability (MSI) and BRAF mutation in colon cancer. Recent investigations suggested that a separate KRAS mutation-associated CIMP subtype (CIMP-low or CIMP2) exists. However, no study has deciphered the interrelationship between KRAS, BRAF, CIMP and locus-specific CpG island methylation, utilizing causal modeling by structure equation model (SEM) analysis. Design: Utilizing the database of 861 colorectal cancers, DNA methylation at 16 CpG islands [CACNA1G, CDKN2A (p16), CHFR, CRABP1, HIC1, IGF2, IGFBP3, MGMT, MINT-1, MINT-31, MLH1, NEUROG1, p14 (CDKN2A/ARF), RUNX3, SOCS1, and WRN] was quantified by real-time PCR (MethyLight). We also examined MSI status and DNMT3B expression. To evaluate the effect of KRAS and BRAF mutation on the correlation structure of the CpG island markers and MSI, we categorized tumors into 4 groups; Group 1 (N=440) with wild-type KRAS and BRAF; Group 2 (N=308) with mutant KRAS and wild-type BRAF; Group 3 (N=107) with wild-type KRAS and mutant BRAF; and Group 4 (N=6) with mutant KRAS and BRAF, which was excluded from further analyses. We analyzed data using clustering analysis, principal component analysis (PCA) and SEM. Results: In unsupervised disjoint clustering analysis of the methylation markers, only 4 markers (CACNA1G, IGF2, RUNX3, SOCS1), were clustered with CIMP-high regardless of KRAS or BRAF mutation. In Groups 1 and 2, two latent CIMP classes, CIMP-low and CIMP-high, were assumed. However, in Group 3, CIMP-high status and CIMP-low status were clustered together so that only one latent class, “CIMP”, was assumed. PCA yielded similar findings to clustering. Based on the results of the cluster analysis and PCA and the literature data, we applied causal modeling by SEM analysis. In SEM analyses, the correlation structures between CIMP, locus-specific CpG island methylation and MSI differed according to KRAS and BRAF status, which was in agreement with results by PCA analyses. Differences between Group 1, Group 2 and Group 3 were highly significant p&amp;lt;0.0001). Conclusions: KRAS and BRAF mutations influence correlation structures between locus-specific CpG island methylation, and CIMP status in colorectal cancer. Our data suggest the role of KRAS and BRAF mutations in modifying propensity of CpG island methylation in a locus-specific manner. 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 4922.
Thomas Addis Emmet and William James MacNeven
Authors: J. Fraser Muirhead
Journal: New England Journal of Medicine (1960)

THE nation has been fortunate in receiving many immigrants who have made important contributions to their adopted land. Two little known examples are Thomas Addis Emmet and William James MacNeven, Irish immigrants of the early nineteenth century and physicians afield in more than one sense.Emmet was born April 25, 1764, in Cork, Ireland, the second son of Robert Emmet, state physician of Dublin. His early education completed with a bachelor's degree from Trinity College, Dublin, he went to Edinburgh University, where he received his medical degree in 1784. Being elected president of no less than five debating societies in . . .
Chemokines and Transplant Vasculopathy
Authors: John A Belperio, Abbas Ardehali
Journal: Circulation Research (2008)

Transplant vasculopathy (TV) remains the leading cause of late death among heart transplant recipients. Transplant vasculopathy is characterized by progressive neointimal proliferation, leading to ischemic failure of the allograft. Multiple experimental and clinical studies have shown that injury to the graft at various stages of transplantation can be a risk factor for development of transplant vasculopathy. The hallmark of cardiac allograft injury is the infiltration of leukocytes. Recruitment of leukocytes requires intercellular communication between infiltrating cells, endothelium, parenchymal cells, and components of extracellular matrix. These events are mediated via the generation of adhesion molecules, cytokines, and chemokines. The chemokines, by virtue of their specific cell receptor expression, can selectively mediate the local recruitment/activation of distinct leukocytes/cells, allowing for migration across the endothelium and beyond the vascular compartment. This report provides a comprehensive review of the chemokines that participate in the development of transplant vasculopathy.
The Cost-effectiveness of Antihypertensive Drugs
Authors: Norman M. Kaplan
Journal: JAMA (1990)

To the Editor.—  In these days of increasing concerns about the steadily escalating costs of medical care in the United States, the publication of the article by Edelson et al 1 showing a sevenfold difference between the cost-effectiveness of different antihypertensive drugs in the treatment of mild to moderate hypertension is sure to receive considerable notice, if not by clinicians certainly by those people who are exerting more and more influence over the way clinicians practice medicine— third-party payers, health maintenance organizations' formulary committees, and health policy planners in Washington. Therefore, all who are interested in providing the best possible care for hypertensive patients ought to be aware that the data used to reach the conclusions of this analysis are seriously flawed.  For example, the authors use as little as a single study involving 12 patients for one drug and compare it with another drug for which data are used
Management of fibrosing pancreatitis in children presenting with obstructive jaundice
Authors: F A Sylvester, B Shuckett, E Cutz, P R Durie, M A Marcon
Journal: Gut (1998)

Background —Children with fibrosing pancreatitis are conventionally treated surgically to relieve common bile duct (CBD) obstruction caused by pancreatic compression. Residual pancreatic function has not been formally tested in these patients. Aims —To evaluate the usefulness of non-surgical temporary drainage in children with fibrosing pancreatitis and to assess pancreatic function after resolution of their CBD obstruction. Patients —Four children (1.5–13 years; three girls). Methods and results —Abdominal sonography and computed tomography revealed diffuse enlargement of the pancreas, predominantly the head. The CBD was dilated due to compression by the head of the pancreas. Pancreatic biopsy specimens obtained in three patients showed notable acinar cell atrophy and extensive fibrosis. Cystic fibrosis was excluded. No other cause of pancreatitis was identified. Pancreatic tissue from one patient contained viral DNA sequences for parvovirus B19 detected by polymerase chain reaction; serum IgM to parvovirus was positive. Three patients had temporary drainage of the CBD and one patient underwent a choledochojejunostomy. Serial imaging studies revealed resolution of the CBD obstruction with reduction in pancreatic size. Exocrine pancreatic function deteriorated. Three patients developed pancreatic insufficiency within two to four months of presentation. The fourth patient has notably diminished pancreatic function, but remains pancreatic sufficient. None has diabetes mellitus. Conclusions —Temporary drainage of the CBD obstruction is recommended in fibrosing pancreatitis in children along with close monitoring of the clinical course, before considering surgery.
THE INCIDENCE AND LOCALIZATION OF ACNE
Authors: E. LIPMAN COHEN.
Journal: British Journal of Dermatology (1945)

Journal Article THE INCIDENCE AND LOCALIZATION OF ACNE Get access E. LIPMAN COHEN. E. LIPMAN COHEN. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 57, Issue 1-2, 1 January 1945, Pages 10–14, https://doi.org/10.1111/j.1365-2133.1945.tb11183.x Published: 01 January 1945
Nuclear localization signal-enhanced RNA interference of EZH2 and Oct4 in the eradication of head and neck squamous Cell carcinoma-derived cancer stem cells
Authors: Wen-Liang Lo, Yueh Chien, Guang-Yuh Chiou, Ling-Ming Tseng, Han-Shui Hsu, Yuh-Lih Chang, Kai-Hsi Lu, Chian-Shiu Chien, Mong-Lien Wang, Yi-Wei Chen, Pin-I. Huang, Fang-Wei Hu, Cheng-Chia Yu, Pen-Yuan Chu, Shih-Hwa Chiou
Journal: Biomaterials (2012)
Biographies medicales et scientifiques, XVIIIe siecle: Jean Astruc, Antoine Louis, Pierre Desault, Xavier Bichat
Authors: Lester S. King
Journal: JAMA (1973)

Present-day scholars in medical history are devoting more and more time to conceptual development in medicine and science, or to the relation of medicine to social and political background, or to the psychological aspects of the physician. But there is still ample room for additional work in the more traditional biographical format and in what may be characterized as bio-bibliography. A new series of biographical studies is now appearing in France, edited by Professor Huard. The first volume contains essays on four 18th-century physicians. The first three biographies are by Huard and Imbault-Huart. They write about Jean Astruc (1684-1766), a physician best known for his work on venereal diseases but a prolific writer on other medical subjects; Antoine Louis (1723-1792), a surgeon who advanced surgical technique, wrote extensively on many surgical topics, and helped to establish the discipline of forensic medicine; and Pierre Desault (1738-1795), an influential surgeon best known
JAMA editorial position and US health system reform
Authors: D. G. Stanley
Journal: JAMA (1994)

To the Editor.  —I and many other medical professionals and patients diametrically oppose theJAMArating of the various health care plans as issued by the Cox News Service and carried in theKnoxville News-Sentinelon Thursday, May 19,1994. Erroneously, the impression was given that the American Medical Association (AMA) represents its physicians in supporting such plans as the Expanded Medicare Bill and President Clinton's plan as the  health care alternatives for everyone.  Certainly, such plans are not best for the public majority. Any plan that seeks to punish patients and physicians for pursuing a maximum level of health care and forces lower standards of care on everyone is unjust and should not be backed by the AMA. A Clinton prototype, TennCare, is already in place in Tennessee and is functioning poorly. Vital personal health decisions are being complicated and made even more stressful and unpredictable by TennCare's third-party
Case 18-1968
Authors: Alexander Leaf, Kilmer S. McCully
Journal: New England Journal of Medicine (1968)

Presentation of CaseFirst admission. A fifty-two-year-old man was admitted to the hospital because of hematemesis and melena.For the previous eighteen months he had consumed between a pint and a quart of whiskey daily. During the year before entry he experienced generalized weakness, and during the two weeks before entry he took aspirin tablets every two hours because of increasing malaise and nausea. Three days before admission he vomited bloody gastric contents and passed several tarry, black stools. There was no history of abdominal pain or a peptic ulcer.On physical examination the lungs and heart were normal. There . . .
Surgical Repair of Rupture of Pectoralis Major Muscle
Authors: Laurence R. Schechter, Anthony G. Gristina
Journal: JAMA (1964)

THE FOLLOWING is a report of a case of complete rupture of the sternal portion of the pectoralis major muscle. Rupture of this muscle is an infrequent occurrence.<sup>1</sup> <h3>Report of a Case</h3> A 41-year-old Negro laborer was admitted to the hospital complaining chiefly of a painless mass of four months' duration in the left pectoral region. Eight months prior to admission the patient suffered multiple injuries to both ankles while sliding from a seven-foot ledge with his arms placed behind him in an attempt to arrest his fall. He had no complaints involving the left shoulder. The next day he noted a painless, ecchymotic area over the left shoulder and anterior portion of the upper arm which lasted several days. It was not until four months later that he noted a mass over the left pectoral region which, according to the patient, enlarged during the following four months prior
Feasibility of early discharge after acute Q wave myocardial infarction in patients not receiving thrombolytic treatment
Authors: Ginés Sanz, Amadeu Betriu, Gloria Oller, Mariona Matas, Jordi Magriñá, Carles Paré, Eulàlia Roig, Magda Heras, Manuel Azqueta, Xavier Bosch, Antonio Serra, Tomás de Flores
Journal: Journal of the American College of Cardiology (1993)
A Theory of the Pathogenesis of Rheumatoid Arthritis
Authors: A. D. Wallis
Journal: Annals of the Rheumatic Diseases (1950)

Another assumed cause of origin for these proliferative joint changes (in rheumatoid arthritis) is that an irritant is produced as the result of ' faulty metabolism', i.e. it is assumed that, on account of some supposed abnormality in physiological processes of certain tracts or organs of the body, or as a result of abnormal cellular changes, a soluble irritant of some unknown sort is produced, which for some unexplained reason selects the joint cavities and epiphyses of the bones as the site of most marked activity. . . .Although with the present state of physiological and chemical knowledge the actual demonstration of such an irritant is impossible, the clinical and pathological facts make the assumption of its existence plausible, and we believe that the etiological factor in the production of many of these joint lesions is explicable on these grounds."(Nichols and Richardson, 1909.)It is with some hesitation that one advances a new theory, particularly in regard to rheumatoid (atrophic) arthritis, which has already been the subject of so much speculation.However, recent observations of Wallis and Horvath (1949) on the tissue-fixation of antibodies may provide a missing link worthy of consideration in the pathogenesis of this type of arthritis.Among the various kinds of arthritis there may be others whose pathogenesis is the same as that of typical adult rheumatoid arthritis, but to avoid unnecessary complications the present discussion is restricted to this disease in its classical form.A fairly symmetrical involvement of the proximal interphalangeal finger joints and a disease duration of one year have been adhered to as minimal requirements in selecting patients for study.There is general agreement that circulating antibodies are capable of becoming temporarily attached to tissue cells.An important site of this fixation is believed to be the walls of blood vessels, especially arterioles.The amounts of tissue-fixed and circulating antibody, while they are not necessarily equal, are known to rise and fall together, in a so-called dynamic equilibrium.The purpose of tissue- fixation of antibody is presumably one of temporary storage.This mechanism, however, has unfortunate side-effects, of which the best known are the sensitivity reactions classifiable under the broad heading of anaphylaxis.These reactions, which vary with the organ and the species, are believed to represent tissue response to the union of tissue-fixed antibody and homologous circulating antigen.While sensitivity reactions may play a part in producing the carditis 331
Abstract 4491: AZD5363, a novel Akt inhibitor, delays prostate cancer progression by inhibiting androgen-receptor activity
Authors: Francois Lamoureux, Christian Thomas, Claire Crafter, Barry Davies, Martin E. Gleave, Amina Zoubeidi
Journal: Cancer Research (2011)

Abstract Introduction and Objective: Despite initial response to androgen deprivation therapy, prostate cancer (PCa) inevitably progresses after 3 to 4 years to its castration-resistant state (CRPC). Consequently, there is an urgent need for novel therapeutic agents that can prevent or at least prolong the time to CRPC progression. The phosphoinositide 3-kinase (PI3K)/Akt pathway plays a key role in tumor progression and therefore is an attractive pharmacological target. In this study, we assessed the anti-cancer effects of the novel and selective Akt inhibitor, AZD5363, in vitro and in vivo in PCa. Methods: LNCaP and C4-2 cells were treated with AZD5363 and submitted to western blot, qRT-PCR and immunofluorescence analysis. AZD5363 was tested for its ability to modulate PSA transactivation by luciferase assay. Cell viability was assessed by crystal violet and cell cycle population by flow cytometry. For in vivo xenograft studies, LNCaP cells were inoculated s.c. in the flank region of athymic nude mice. Mice were castrated and randomly treated with AZD5363 or control by oral gavage. Tumor volume and serum prostate-specific antigen (PSA) were evaluated twice per week. Results: Here we report that AZD5363 inhibits cell growth in a dose-dependent manner (IC50 ± 200nM) in both LNCaP and C4-2, induces cell apoptosis as measured with PARP cleavage expression, Caspase 3 activity, and increases sub-G1 population (20.2% and 22.2% at 500nM for LNCaP and C4-2 cells, respectively). Interestingly, AZD5363 significantly abrogates androgen-induced PSA transactivation at concentrations &amp;gt; ∼100nM and down-regulates AR expression at concentrations &amp;gt; ∼1μM. These biologic events were accompanied by inhibition of downstream PI3K/Akt signaling. Most important, targeting the Akt-pathway in vivo significantly reduces tumor volume and serum PSA-levels and thereby delays progression to CRPC. Conclusions: This study reports as a preclinical proof-of-principle that targeting PI3K/Akt pathway with AZD5363 inhibits androgen-dependent PCa progression in vitro and in vivo, using the AR-axis as a pharmacodynamic tool. This work was supported by AstraZeneca, the Deutsche Forschungsgemeinschaft (German Research Foundation; Grant number: TH 1482/2-1), the Canadian Institutes of Health Research and l'Association pour la Recherche sur le Cancer (France). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4491. doi:10.1158/1538-7445.AM2011-4491
Anti-inflammatory Effects Of A Purified Herbal Flavanoid 7, 4' Dihydroxy Flavone In Vivo And In A Murine Model
Authors: S.P. Patil, B. Jayaprakasam, S. Bezdecny, S. Doddaga, E. Rusinova, X. Li
Journal: Journal of Allergy and Clinical Immunology (2009)
UTILITY OF A MULTIPLE BIOMARKER INDEX IN ASYMPTOMATIC ADULTS DEPENDS ON ATHEROSCLEROTIC BURDEN
Authors: Nathan D. Wong, Heidi Gransar, Jamal S. Rana, Johanna Kim, Romalisa Miranda-Peats, Leslee Shaw, Alan Rozanski, Sean Hayes, Louise Thomson, John Friedman, Daniel S. Berman
Journal: Journal of the American College of Cardiology (2010)
Task force III: Major demographic and epidemiologic trends affecting adult cardiology
Authors: Robert L. Frye, Millicent W. Higgins, George A. Beller, John A. Benson, Jeffrey S. Borer, Charles L. Curry, Bernard J. Gersh, Lee Goldman, Francis J. Klocke, Daniel D. Savage, John F. Williams
Journal: Journal of the American College of Cardiology (1988)
Evidence of Systemic Th2-Driven Chronic Inflammation in Patients with Metastatic Melanoma
Authors: Wendy K. Nevala, Celine M. Vachon, Alexey A. Leontovich, Christopher G. Scott, Michael A. Thompson, Svetomir N. Markovic
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Immunotherapeutic modalities are commonly used for treatment of patients with melanoma. The therapeutic success in preclinical models has not yielded the expected clinical results. To understand this discrepancy, we attempted to define immune homeostasis of 209 patients with melanoma across stages of disease relative to normal controls. Experimental Design: Peripheral blood mononuclear cells (PBMC) and plasma were collected from patients and healthy donors. PBMC were analyzed for frequencies of natural killer, dendritic, and T cells and their functional status. Matched plasma samples were analyzed for the concentrations of 27 cytokines, chemokines, and growth factors. RNA was isolated from 24 metastatic melanoma tumor biopsies and profiled by microarray analysis. Results: The frequency of natural killer, T, and dendritic cells in patients does not significantly change across stages of melanoma. However, plasma concentrations of Th2 cytokines [interleukin (IL)-4, IL-5, IL-10, and IL-13] in tumor-bearing patients were significantly higher than those with resected melanoma. Expression array analysis of metastatic melanoma revealed that the malignant melanocytes were not the source of the Th2 cytokines but did highly up-regulate vascular endothelial growth factor (VEGF) transcripts, consistent with plasma VEGF concentrations. In vitro VEGF exposure of normal PBMC lead to repolarization from Th1 to Th2 emulating the state of metastatic melanoma. Conclusions: Patients with metastatic melanoma exist in a state of Th2-mediated “chronic inflammation” as a result of at least VEGF overproduction by malignant tumors. These data support prior observations regarding the effect of VEGF on immune cell function and suggests consideration of VEGF inhibitors in future cancer immunotherapy clinical studies in metastatic melanoma.
Venous leg ulcers: a prognostic index to predict time to healing.
Authors: A. I. Skene, J. M. Smith, C. J. Dore, A. Charlett, J. D. Lewis
Journal: BMJ (1992)

OBJECTIVE--To evaluate the prognostic factors in uncomplicated venous leg ulcer healing. DESIGN--Randomised parallel group controlled trial with subjects stratified by initial ulcer diameter and four months9 maximum duration of follow up. SETTING--Assessment at Northwick Park Hospital vascular unit with community based treatment. PATIENTS--200 patients with clinical and objective evidence of uncomplicated venous leg ulceration and an initial ulcer diameter &gt; 2 cm. MAIN OUTCOME MEASURE--Time to complete healing of the ulcer. RESULTS--In the presence of graduated compression healing occurred more rapidly in patients with a smaller initial ulcer area (relative risk of healing 1.92 associated with halving of ulcer area (95% confidence interval 1.58 to 2.33)), shorter duration of ulceration (relative risk 1.35 associated with halving duration (1.17 to 1.56)), younger age (relative risk 1.34 associated with 10 year decrease (1.12 to 1.59)), and no deep vein involvement (relative risk 1.8 (1.19 to 2.78)). CONCLUSION--These prognostic factors used in a simple scoring system predict time to healing.
Is There a Predisposition to Intestinal Parasitosis in Diabetic Patients?
Authors: Yasar Nazligul, Tevfik Sabuncu, Hatice Ozbilge
Journal: Diabetes Care (2001)

Although intestinal parasites usually create benign diseases, sometimes they may cause complications with high mortality and morbidity (1,2). It is known that diabetic patients are more susceptible to bacterial infections. Decreased arterial perfusion, neuropathy, and suppressed immune response in diabetes aggravate the frequency and severity of infectious diseases (3). Lymphocyte and polymorphonuclear leukocyte functions are altered (4). The most prominent alteration is the phagocytic functions of polymorphonuclear leukocytes (5,6). It has also been reported that candidal infections occur more frequently in diabetic patients than in nondiabetic control subjects (7,8). Is a similar kind of predisposition present against parasitic infections, particularly against the intestinal parasites in diabetic patients? There is no adequate study about this subject. Therefore, we assessed whether there is a predisposition against intestinal parasites in the diabetic population by comparing their prevalence in diabetic and nondiabetic individuals living in the Sanliurfa province, which lies in southeast Anatolia. …