tbuckley/cabot-search huggingface dataset:
Cholera Toxin Suppresses Interleukin (IL)-12 Production and IL-12 Receptor β1 and β2 Chain Expression
Authors: Michael C. Braun, Jianping He, Chang-You Wu, Brian L. Kelsall
Journal: The Journal of Experimental Medicine (1999)

Cholera toxin (CT) is a potent mucosal vaccine adjuvant, which has been shown to induce T helper cell type 2 (Th2) responses in systemic and mucosal tissues. We report that CT inhibits the production of interleukin (IL)-12, a major Th2 counterregulatory cytokine. IL-12 p70 production by stimulated human monocytes was inhibited by CT in a dose-dependent manner. This suppression occurred at the level of gene transcription, was maximal at low concentrations of CT, and was dependent on the A subunit of the toxin, since purified CT B subunit had minimal effect. CT also inhibited the production of IL-12 p70 by monocyte-derived dendritic cells, as well as the production of tumor necrosis factor alpha, but not IL-10, IL-6, or transforming growth factor (TGF)-beta1, by stimulated monocytes. The effects of CT were not due to autocrine production of IL-10, TGF-beta1, or prostaglandin E2. CT inhibited the production of IFN-gamma by anti-CD3-stimulated human peripheral blood mononuclear cell, due in part to suppression of IL-12 production, but also to the inhibition of expression of the beta1 and beta2 chains of the IL-12 receptor on T cells. In vivo, mice given CT before systemic challenge with lipopolysaccharide had markedly reduced serum levels of IL-12 p40 and interferon gamma. These data demonstrate two novel mechanisms by which CT can inhibit Th1 immune responses, and help explain the ability of mucosally administered CT to enhance Th2-dependent immune responses.
Review of Alireza Bagheri, ed.,<i>Medical Futility: A Cross-National Study</i>
Authors: James J. Rusthoven
Journal: The American Journal of Bioethics (2014)

"Review of Alireza Bagheri, ed., Medical Futility: A Cross-National Study ." The American Journal of Bioethics, 14(1), pp. 52–53 Notes 1. London, UK: Imperial College Press, 2013, 312 pp. $98.00 USD, hardcover.
Hormone Levels During Dietary Changes in Premenopausal African-American Women
Authors: Margo N. Woods, Junaidah B. Barnett, Donna Spiegelman, Nancy Trail, Ellen Hertzmark, Christopher Longcope, Sherwood L. Gorbach
Journal: JNCI Journal of the National Cancer Institute (1996)

Background:In the United States, 5-year survival rates of 69% and 84%, respectively, have recently been reported for African-American and Caucasian women diagnosed with breast cancer. Differences in the levels of endogenous sex hormones in these populations could explain some of the variation in survival rates, since estrogen is recognized as a risk factor for this type of cancer.
Clinical Lecture on the Administration of Chloroform
Authors: G. H. B. Macleod
Journal: BMJ (1876)

Concluded from page 7 of last number.In the first part of this paper, at page 5, column i. line 5 from bottom, for " individual", read " tindivided"; anid in column 2a line 26 from bottom, for "meat, soup, and bread", read " meat-soup and bread".
St Ronald and the dragons.
Authors: G Dunea
Journal: BMJ (1984)

authors of this report concluded that it had not been possible to predict the ultimate neurological outcome of a patient with a head injury on the basis of initial examination.They suggested that the orthopaedic surgeon should proceed on the basic assumption of full neurological recovery.Having achieved the best possible resuscitative state a general anaesthetic was permissible if the patient's state remained stable during an immediate observation period.Thus operations on fractured femurs could be performed within eight hours of injury.5We agree with an aggressive approach to operative reduction in cases of injury to major joints associated with head injury.This should reduce musculoskeletal morbidity in the patient with a head injury and will minimise the type of unfortunate conse- quences shown in the case reported.References
Considerations for Diabetes Translational Research in Real-World Settings
Authors: Sanford A. Garfield, Saul Malozowski, Marshall H. Chin, K.M. Venkat Narayan, Russell E. Glasgow, Lawrence W. Green, Roland G. Hiss, Harlan M. Krumholz
Journal: Diabetes Care (2003)

IDDK's mission is to conduct and support research on diseases such as diabetes in order to increase knowledge to improve the public's health.NIDDK's goals will not be completely achieved until the knowledge gained from the research it supports is translated and fully applied.
Maladaptive Remodeling Is Associated With Impaired Survival in Women But Not in Men After Aortic Valve Replacement
Authors: George Petrov, Elke Dworatzek, Tabea Marie Schulze, Michael Dandel, Georgios Kararigas, Shokufeh Mahmoodzadeh, Christoph Knosalla, Roland Hetzer, Vera Regitz-Zagrosek
Journal: JACC. Cardiovascular imaging (2014)

The purpose of this study was to test whether adaptive or maladaptive remodeling is associated with survival in women and men after aortic valve replacement (AVR). Women with isolated aortic valve stenosis (AS) develop more concentric left ventricular hypertrophy (LVH) than men in similar disease states. We recently reported less up-regulation of profibrotic genes at AVR and faster LVH regression post-operatively in women than in men, suggesting that there are sex differences in the adaptation to pressure overload and its regression. The study cohort included 128 patients (age 70.0 ± 9.6 years, 49% women) undergoing AVR for AS. Echocardiography was obtained before and 4.0 ± 1.6 years after surgery. Factor analysis was used to classify LVH as adaptive (combining smaller left ventricular [LV] mass/diameters and greater relative wall thicknesses) or maladaptive. Myocardial tissue samples from the LV septum were obtained during AVR to analyze cardiac fibrosis and associated key molecular regulators. Before AVR, LVH was classified as adaptive in 62% of women and 45% of men (p < 0.050). Four years after AVR, adaptive LVH was observed in 75% of women and 49% of men (p < 0.031). At surgery, more cardiac fibrosis was present in men compared with women (p < 0.05). Higher levels of transforming growth factor beta 1 (p < 0.01), SMAD2 phosphorylation (p < 0.001), and periostin expression (p < 0.05) were found in men than in women. Women with maladaptive LVH had worse survival than women with adaptive LVH (p < 0.050), whereas the pattern of LVH did not affect survival in men (p < 0.307). Women more frequently exhibit adaptive LV remodeling with less fibrosis than men. Maladaptive LVH is associated with worse survival in women. Thus, sex should be considered as a strong modulating factor when management of patients with AS is discussed.
Argon plasma coagulation has a long-lasting therapeutic effect in patients with chronic radiation proctitis
Authors: G. Karamanolis, K. Triantafyllou, Z. Tsiamoulos, D. Polymeros, T. Kalli, N. Misailidis, S. Ladas
Journal: Endoscopy (2009)

Background and study aims: The optimal treatment of bleeding due to radiation proctitis is still controversial. Although argon plasma coagulation (APC) has been recently reported as an effective treatment, its efficacy in relation to disease severity is unknown. The study aims were to prospectively evaluate (i) the efficacy of APC in endoscopically mild and severe radiation proctitis, and (ii) the recurrence rate following successful treatment.
Semantic Hypersensitivity to Penicillin?
Authors: Morris J. Finer
Journal: JAMA (1964)

<h3>To the Editor:—</h3> The selection of a title for scientific papers is a serious responsibility. An inaccurate choice of words can convey an unwarranted impression and make medico-legal misinterpretation possible. For example, the contribution entitled "Brain Damage Due to Penicillin" (<i>JAMA</i><b>186</b>:899 [Dec 7] 1963) describes a long-known sequel to cerebral hypoxia resulting from<i>any</i>cause of brain ischemia. The title implies that the brain damage was uniquely and specifically attributable to penicillin as one of its possible adverse pharmacological properties. A more truthful choice of words would be "Brain Damage Following Anaphylactic Shock." The case histories do not sustain the proposition that penicillin per se will produce brain damage. Let us not provide litigious attorneys or clients with illusory material based on semantic carelessness.
Recent developments in carbohydrate‐decorated targeted drug/gene delivery
Authors: Hailong Zhang, Yong Ma, Xue‐Long Sun
Journal: Medicinal Research Reviews (2009)

Abstract Targeted delivery of a drug or gene to its site of action has clear therapeutic advantages by maximizing its therapeutic efficiency and minimizing its systemic toxicity. Generally, targeted drug or gene delivery is performed by loading a macromolecular carrier with an appropriate drug or gene, and by targeting the drug/gene carrier to specific cell or tissue with the help of specific targeting ligand. The emergence of glycobiology, glycotechnology, and glycomics and their continual adaptation by pharmaceutical scientists have opened exciting avenue of medicinal applications of carbohydrates. Among them, the biocompatibility and specific receptor recognition ability confer the ability of carbohydrates as potential targeting ligands for targeted drug and gene delivery applications. This review summarizes recent progress of carbohydrate‐decorated targeted drug/gene delivery applications. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 2, 270–289, 2010
Low serum C4 concentrations and microangiopathy in type I and type II diabetes.
Authors: M E Cooper, R Duff, R Buchanan, J McPherson, G Jerums
Journal: BMJ (1986)

hospitals were attributed to publicity about overuse.4In our hospital use of chest radiography has fallen by 55% since the first survey.That appropriate use has been sustained or improved is suggested by a small increase in the proportion of patients admitted with an abnormal chest x ray film.The increased proportion of examinations showing significant abnormality from 90/o to 24% suggests a reduction in routine or screening radiography.The findings suggest that in adult psychiatry chest radiography should be used when there is clinical evidence ofcardiothoracic disease or unexplained failure of an episode of mental illness to remit, and screening should be confined to alcoholism.'A reduction of 51% in the use of skull radiography occurred after guidelines were issued to junior staff assessing head injuries.5In our hospital the use of skull radiography has fallen by 42% since the first survey.All patients with an abnormality on computed tomography showed normal results on skull radiography.Skull radiography is thus not useful in adult psychiatry.The use of computed tomography increased from 0-8% to 3-3% of admissions.The proportion ofabnormal results increased from 31% to 36%, suggesting that clinical judgment is improving.Abnormal radiological findings were confined to patients with clinical evidence of organic brain disease.Prolonged or atypical affective psychoses accounted for most normal scans.The findings suggest that in adult psychiatry computed tomography is of value only when there are symptoms or signs of neurological disease.1 Vergani D, Johnston C, Abdullah NB, Barnett AH.Low serum C4 concentrations: an inherited predisposition to insulin dependent diabetes.
Abstract 5142: VEGFA gene amplification and protein expression in breast cancer
Authors: Mariacarla Andreozzi, Sandra Schneider, Inti Zlobec, Coya Tapia, Luigi Tornillo, Serenella Eppengerger, Luigi Terracciano, Christian Ruiz
Journal: Cancer Research (2011)

Abstract Background: The vascular endothelial growth factor A (VEGFA) protein is a chemical signaling molecule that is known to be a major factor in the induction of angiogenesis during tumor initiation and progression, and is also a target of anti-angiogenic therapies. Recently, we discovered the genomic amplification of the VEGFA gene in a small subset of colorectal cancers. Aim of this study was to investigate the presence of VEGFA gene amplification in breast cancer and to determine its potential impact on VEGFA protein expression. Methods: VEGFA gene amplification was evaluated by fluorescence in situ hybridization (FISH) on a multitumor tissue microarray (MTMA) comprising 3417 tissue samples from more than 100 different tumor types. Further, a small tissue microarray was constructed from breast carcinoma samples whose VEGFA protein concentration had been previously quantified by chemiluminescence immunoassay. In order to interrogate tissue heterogeneity, VEGFA gene amplification was also analyzed on large tissue sections from 70 primary breast cancers. Results: We detected VEGFA gene amplification in 2% of the breast cancer samples from the MTMA and in 5% of the breast cancer samples with known VEGFA protein concentration. In addition, 8% of the samples (5 out of 70) were characterized by a high polysomy. Interestingly, elevated VEGFA gene copy number was strongly correlated with higher VEGFA protein levels (p&amp;lt;0.0001). Conclusions: VEGFA gene amplification defines a small subset of breast carcinomas with elevated VEGFA protein expression. Our data suggest that FISH analysis of VEGFA could represent an additional evaluation system for the identification of breast cancer patients who might benefit from anti-VEGFA therapies. 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 5142. doi:10.1158/1538-7445.AM2011-5142
The Little Bighorn River
Authors: Curt Kurtz
Journal: JAMA (1968)

<h3>To the Editor:—</h3> The editorial (<b>203</b>: 44, 1968) had Custer making his last stand in Wyoming. As the current Medicine Man for the fighting Cheyennes, I am stationed only a few miles to the east of the famous battleground along the Little Bighorn. We are in Montana, and Wyoming is nearly 100 miles away.
Safety of the Blood Supply
Authors: Elaine M. Sloand
Journal: JAMA (1995)

IN THE YEARS following the emergence of the human immunodeficiency virus type 1 (HIV-1) infection as a transfusion-transmitted disease, both the general public and the medical profession have voiced great concern about the safety of the blood supply. Although improved donor screening and testing have greatly increased blood safety, a 1993 Gallup survey<sup>1</sup>showed that concern about acquired immunodeficiency syndrome (AIDS) far exceeded that for heart or lung disease, despite the greater health risk these latter pose. Widely publicized shortcomings in the conduct of several blood collecting agencies in Europe and the United States have only heightened public fear. As the number of measures to promote safety increases, their value must be weighed against many other considerations, such as wastage of discarded blood and unnecessary loss of potential donors due to false-positive results, direct costs of additional or more technologically demanding tests, the increased risk of errors with additional
The Risk of Breast Cancer in American Women
Authors: Richard R. Love
Journal: JAMA (1987)

<h3>To the Editor.—</h3> It is often asserted that "one out of every 11 women in this country will develop breast cancer at some point in her life" (US Department of Health and Human Services Secretary Margaret M. Heckler, Nov 13, 1985). This statement misrepresents the risk (the probability of a specific event over a specified interval) of breast cancer to American women and is misinterpreted and misused by many. The statistical basis for this specific number derives from a calculation, using life-table methods, of the cumulative probability of developing breast cancer each year from ages 1 to 85.<sup>1</sup>That this number is, or might be, an accurate reflection of the experience of any group of women depends on the stability of the age-specific incidence rates over life-times. In fact, age-specific breast cancer incidence rates are probably changing.<sup>2</sup>Of greater concern, however, is that individual women assume that this
Comment évaluer les variations de rendement entre endoscopistes dans le programme national de dépistage organisé du cancer colorectal par Hemoccult?
Authors: B Denis, EA Sauleau, I Gendre, P Perrin
Journal: Endoscopy (2010)

Objectif: Le taux de détection des adénomes au sein du programme national de dépistage organisé (DO) du cancer colorectal (CCR) par Hemoccult a été proposé pour évaluer la qualité des coloscopies (1). Le but de ce travail était de définir le(s) indicateur(s) de rendement diagnostique le(s) mieux approprié(s) pour une utilisation en routine et d'établir un standard.
Evidentiary Rationales for the Choosing Wisely Top 5 Lists
Authors: Catherine Gliwa, Steven D. Pearson
Journal: JAMA (2014)

Aiming to reduce wasteful medical care, the American Board of Internal Medicine (ABIM) Foundation’s Choosing Wisely initiative asks leading physician specialty societies to create a “Top 5” list of medical services that provide no overall benefit to patients in most situations.1,2 As of August 2013, 25 participating specialty societies had produced 1 or more Top 5 lists containing a total of 135 services.

The goal of this study was to evaluate the role that evidence on benefits, risks, and costs plays in selecting a service for the Top 5 lists. As Choosing Wisely continues to grow, clarity on the evidentiary justifications for the lists will be crucial for the overall credibility of the campaign.
Blastic natural killer-cell lymphoma of the skin associated with myelodysplastic syndrome or myelogenous leukaemia: a coincidence or more?
Authors: D.V. Kazakov, T. Mentzel, G. Burg, R. Dummer, W. Kempf
Journal: British Journal of Dermatology (2003)

We report three patients with blastic natural killer (NK)-cell lymphoma of the skin associated with myelodysplastic syndrome (MDS) (two patients) or subacute myelomonocytic leukaemia (one patient). In two patients MDS was diagnosed before skin lesions; the patient with leukaemia initially presented with skin lesions. Our patients had several clinical features in common, namely multiple skin lesions with a bruise-like appearance, involvement of the oral mucosa, and good general status at presentation but very rapid deterioration in the course of the disease. All patients died of disease 4-14 months after the diagnosis. Histopathologically, there were cutaneous infiltrates of slightly pleomorphic medium-sized cells expressing CD4, CD56, terminal deoxynucleotidyl transferase (focally) and being negative for surface CD3, cytotoxic molecules, B-cell-associated markers and myelomonocytic markers. Erythrocyte extravasation was seen in all patients. T-cell receptor genes were in germline configuration. MDS was classified as refractory cytopenia with multilineage dysplasia and ring sideroblasts and refractory anaemia with transition to refractory anaemia with excess of blasts. We reviewed similar cases reported in the literature showing coexistence of blastic NK-cell lymphoma/leukaemia and MDS or myelogenous leukaemia. We conclude that given an overall limited number of reported cases of blastic NK-cell lymphoma/leukaemia, its association with various myelodysplastic/myeloproliferative disorders seen in a subset of patients ( approximately 15-20%) is more than coincidental and may indicate their common origin.
Protective role of V-set and immunoglobulin domain-containing 4 expressed on kupffer cells during immune-mediated liver injury by inducing tolerance of liver T- and natural killer T-cells
Authors: Keunok Jung, Miseon Kang, Cheol Park, Yung Hyun Choi, Youkyung Jeon, Se-Ho Park, Su-Kil Seo, Dan Jin, Inhak Choi
Journal: Hepatology (2012)

V-set and Ig domain-containing 4 (VSIG4, CRIg, or Z39Ig), a newly identified B7-related cosignaling molecule, is a complement receptor and a coinhibitory ligand that negatively regulates T-cell immunity. Despite its exclusive expression on liver Kupffer cells (KCs) that play key roles in liver tolerance, the physiological role of VSIG4 in liver tolerance remains undefined. Mice lacking VSIG4 had poor survival rates and severe liver pathology in a concanavalin A (ConA)-induced hepatitis (CIH) model, which could be prevented by adoptive transfer of VSIG4(+) KCs. The absence of VSIG4 rendered endogenous liver T- and natural killer T (NKT)-cells more responsive to antigen-specific stimulation and impaired tolerance induction in those cells against their cognate antigens. T-cell costimulation with VSIG4.Ig suppressed Th1-, Th2-, and Th17-type cytokine production and arrested the cell cycle at the G(0) /G(1) phase but did not induce apoptosis in vitro. VSIG4-mediated tolerance induction and cell-cycle arrest were further supported by down-regulation of G(1) phase-specific Cdk2, Cdk4, and Cdk6, and up-regulation of tolerance-inducing p27(KIP-1) in VSIG4.Ig-stimulated T-cells. Administration of soluble VSIG4.Ig to wildtype mice prevented CIH development and prolonged the survival of mice with established CIH.Collectively, our results suggest that VSIG4(+) KCs play a critical role in the induction and maintenance of liver T- and NKT-cell tolerance, and that modulation of the VSIG4 pathway using a VSIG4.Ig fusion protein may provide useful immunological therapies against immune-mediated liver injury including autoimmune hepatitis.
Antibody‐Dependent Monocyte‐Mediated Cytotoxicity in Atopic Dermatitis
Authors: K. Kragballe, T. Herlin
Journal: Allergy (1981)

Antibody‐dependent monocyte‐mediated cytotoxicity was investigated in adult patients with atopic dermatitis. In patients with active dermatitis monocyte cytotoxicity was reduced. Serial studies of individual patients demonstrated that a reduced cytotoxicity in clinical exacerbation did not normalize during clinical remission. The reduced monocyte cytotoxicity was not caused by an abnormal influence of lymphocytes. During the cytotoxicity reaction a rapid and transient elevation of monocyte cyclic AMP occurred. In atopic dermatitis this elevation was decreased, but no relation was found between the monocyte cytotoxicity and the cyclic AMP response in these patients.
G <sub>13</sub> -Mediated Signaling Pathway Is Required for Pressure Overload–Induced Cardiac Remodeling and Heart Failure
Authors: Mikito Takefuji, Angela Wirth, Martina Lukasova, Seiko Takefuji, Thomas Boettger, Thomas Braun, Till Althoff, Stefan Offermanns, Nina Wettschureck
Journal: Circulation (2012)

Cardiac remodeling in response to pressure or volume overload plays an important role in the pathogenesis of heart failure. Various mechanisms have been suggested to translate mechanical stress into structural changes, one of them being the release of humoral factors such as angiotensin II and endothelin-1, which in turn promote cardiac hypertrophy and fibrosis. A large body of evidence suggests that the prohypertrophic effects of these factors are mediated by receptors coupled to the G(q/11) family of heterotrimeric G proteins. Most G(q/11)-coupled receptors, however, can also activate G proteins of the G(12/13) family, but the role of G(12/13) in cardiac remodeling is not understood.We use siRNA-mediated knockdown in vitro and conditional gene inactivation in vivo to study the role of the G(12/13) family in pressure overload-induced cardiac remodeling. We show in detail that inducible cardiomyocyte-specific inactivation of the α subunit of G(13), Gα(13), does not affect basal heart function but protects mice from pressure overload-induced hypertrophy and fibrosis as efficiently as inactivation of Gα(q/11). Furthermore, inactivation of Gα(13) prevents the development of heart failure up to 1 year after overloading. On the molecular level, we show that Gα(13), but not Gα(q/11), controls agonist-induced expression of hypertrophy-specific genes through activation of the small GTPase RhoA and consecutive activation of myocardin-related transcription factors.Our data show that the G(12/13) family of heterotrimeric G proteins is centrally involved in pressure overload-induced cardiac remodeling and plays a central role in the transition to heart failure.