tbuckley/cabot-search huggingface dataset:
Abstract 2323: Molecular modeling studies of the STAT3 homodimer:DNA complex
Authors: Jarmila Husby, Shozeb M. Haider, Giovanna Zinzella, David E. Thurston, Stephen Neidle
Journal: Cancer Research (2011)

Abstract Signal Transducers and Activators of Transcription (STAT) are a group of latent cytoplasmic transcription factors in cytokine signaling, that transduce signals from the cell membrane to the nucleus, where they activate gene transcription. STAT activation by phosphorylation is mediated by growth factors or cytokines, inducing STAT:STAT dimer formation between two monomers via reciprocal phosphoTyr formation. A member of the STAT family, STAT3 (Figure 1), has been found to be expressed at elevated levels in a large number of diverse human cancers, thus STAT3 represents a validated target for anticancer drug design. Understanding the dynamics of the STAT3 dimer interface, accounting for both protein-DNA and protein-protein interactions, with respect to the dynamics of the latent, unphosphorylated STAT3 monomer, is important for designing potential small-molecule inhibitors of the activated dimer. The results of molecular dynamics (MD) simulations of the activated STAT3 homodimer:DNA complex, and latent unphosporylated STAT3 monomer in explicit water have been studied. Careful analysis of the data obtained from MD simulations over a 35 ns time-frame has revealed the dynamics of the macromolecular complex at the atomistic level; how the transcription factor interacts with the DNA, the nature of the conformational changes, and the way function may be affected. Further analysis of the dimer interface, with a main focus on the protein-DNA interaction, including the water molecules, has revealed the key residues contributing to the recognition events involved in STAT3 protein-DNA interactions. Moreover, locations of the majority of mutations in the DNA-binding domain are found at the protein-DNA interface. In particular, we have been able to map out these mutations in detail and relate them to specific protein-DNA contacts. Their structural stability and importance will be described, along with a discussion of how this model is being used to assist in the discovery of novel small-molecule inhibitors. 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 2323. doi:10.1158/1538-7445.AM2011-2323
Effects of renin-angiotensin system blockade on renal angiotensin-(1-7) forming enzymes and receptors
Authors: Carlos M. Ferrario, Jewell Jessup, Patricia E. Gallagher, David B. Averill, K. Bridget Brosnihan, E. Ann Tallant, Ronald D. Smith, Mark C. Chappell
Journal: Kidney International (2005)
Shared decision making in a publicly funded health care system
Authors: M. J Sculpher, I. Watt, A. Gafni
Journal: BMJ (1999)

Imagine you are a general practitioner. A middle aged male patient of yours has taken a cholesterol test at a pharmacy which showed raised concentrations and wants to discuss his treatment options. Following sound evidence1 and national guidelines,2 you tell him that, because he has no other risk factors, medical intervention is not warranted. However, the patient knows that recent trial evidence shows that statins can reduce cardiac events even in populations with mildly raised total cholesterol concentrations.3 You know that such use could greatly increase the cost of such drugs—to as much as £3.5bn in England,4 from £113m in 1997.1

You support shared decision making with patients,5 6 but you recognise the dilemma here: should you see yourself as the agent of the patient, focusing on the effectiveness of treatments, or of the healthcare system and the population it serves, focusing on affordability?

If you choose the system perspective there is more scope for conflict between you and the patient about the treatment of choice. In some cases conflict can arise because the patient's choice is likely to affect …
Women, Health, and Medicine in America: A Historical Handbook
Authors: Virginia U. Collier
Journal: JAMA (1991)

This book is a collection of 20 essays by contemporary historians and sociologists designed to provide an overview of the available literature dealing with the health experiences of women in America. It was conceived to be a single source to which historians and other scholars could turn for a survey of current concepts in women's health history.  The book succeeds in providing a descriptive anthology of important historical papers, books, and monographs on varied subjects including orthodox health care (chapters on women and mental illness, gynecology, obstetrics, and reproductive health) and health care providers (chapters on midwives, nurses, physicians, and pharmacists). The extensive Bibliography by Topic chapter will be of special use to scholars. Among the contributors, 22 of 26 are female.  The majority of the chapters contain social comment, which seems to me not directly pertinent to the stated purpose of the book. The chapter on nurses, a well-written
Letter: Irradiation treatment of rheumatoid arthritis.
Authors: H M Gumpel
Journal: BMJ (1973)

Brief criticism is made of a previous editorial (Brit. Med. J., Vol. 3 No. 5674 4 Aug. 1973) concerning irradiation treatment of rheundatoid arthritis. Attention is drawn to the omission of references to European literature other than English. The dangers of the BETA emission of /sup 90/Y are mentioned, and it is pointed out that French workers use /sup 90/Y in the knees, /sup 186/Re in other large joints, and /sup 169/Er in finger joints. Mention is made of the emphasis on indndobilization of the treatcd joint, both to reduce chromosome damage and to reduce the extra-articular spread of radiocolloid after insection. (UK)
THE PREVENTION OF TETANUS.
Authors: DANIEL N. EISENDRATH
Journal: JAMA (1904)

Much has been written during the past ten years concerning the symptoms and treatment of tetanus, and especially the frequency with which it followed all varieties of punctured wounds. Little, however, has been written as to definite methods for the prevention of this dread disease, and it has always seemed to me that this aspect has not been sufficiently dwelt on. We usually associate tetanus with Fourth of July wounds, but it is almost as frequent after punctured wounds received by rusty nails or pitchfork injuries as after blank cartridges. Why these three classes of injuries should be followed by tetanus can not be explained on any other ground than that in the case of blank cartridges the latter itself is free from tetanus, but that the hand or foot or face, which are the most frequent sites of infection, are more or less covered with street dirt containing
Modifiable Risk Factors for Pulmonary Embolism
Authors: Brian R. Landzberg
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Dr Goldhaber and colleagues have published a worthy study<sup>1</sup>looking at risk factors associated with pulmonary embolism in women. It is certainly useful, though not surprising, to hear that it confirmed that obesity, cigarette smoking, and hypertension portend an increased risk for thromboembolic events. My comment, however, pertains to wording used in the closing sentence of the article's abstract, which states that not only are the above variables correlated with pulmonary embolism, but that control of these risk factors will decrease the risk of same. There is, in fact, no evidence in the study presented that control of obesity, smoking, or hypertension will reduce the risk of pulmonary embolism, only that there exists a positive association. In counseling patients about control of these adverse behaviors and conditions, clinicians tend to infer that risk factor modification will lead to reduction in the incidence of pulmonary embolism (as
Maid (GCIP) is involved in cell cycle control of hepatocytes
Authors: Eva Sonnenberg-Riethmacher, Torsten Wüstefeld, Michaela Miehe, Christian Trautwein, Dieter Riethmacher
Journal: Hepatology (2007)

The function of Maid (GCIP), a cyclinD-binding helix-loop-helix protein, was analyzed by targeted disruption in mice. We show that Maid function is not required for normal embryonic development. However, older Maid-deficient mice-in contrast to wild-type controls--develop hepatocellular carcinomas. Therefore, we studied the role of Maid during cell cycle progression after partial hepatectomy (PH). Lack of Maid expression after PH was associated with a delay in G1/S-phase progression as evidenced by delayed cyclinA expression and DNA replication in Maid-deficient mice. However, at later time points liver mass was restored normally.These results indicate that Maid is involved in G1/S-phase progression of hepatocytes, which in older animals is associated with the development of liver tumors.
A Tumor-stroma Targeted Oncolytic Adenovirus Replicated in Human Ovary Cancer Samples and Inhibited Growth of Disseminated Solid Tumors in Mice
Authors: M Veronica Lopez, Angel A Rivera, Diego L Viale, Lorena Benedetti, Nicasio Cuneo, Kristopher J Kimball, Minghui Wang, Joanne T Douglas, Zeng B Zhu, Alicia I Bravo, Manuel Gidekel, Ronald D Alvarez, David T Curiel, Osvaldo L Podhajcer
Journal: Molecular Therapy (2012)

Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 10(10) v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15-40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression.
The Diagnosis of Art: exophthalmos--Gustave Dore's ogre
Authors: Jeffrey K Aronson, Manoj Ramachandran
Journal: Journal of the Royal Society of Medicine (2006)

Gustave Dore (1832-1883) was France's greatest illustrator. He first came to prominence through his illustrations for Rabelais's Gargantua et Pantagruel (1854) and Balzac's Contes Drolatiques (1856). Other works that he illustrated included Dante's La Divina Commedia, starting with the Inferno in 1861 and adding the Purgatorio and Paradiso in 1886-1888, Don Quixote de la Mancha (1862), the Bible (1865), Paradise Lost (1866), Raspe's Adventures of Baron Munchausen (1866), La Fontaine's Fables (1867), and Coleridge's Rime of the Ancient Mariner (1870). Although primarily a humorous illustrator, Dore was attracted by the darker side of Dickens's works and illustrated them in sombre engravings. Those who have seen Roman Polanski's recent version of Oliver Twist will have appreciated the use that he made of Dore's work as backdrops to the opening titles. Dore's interest in London was stimulated by Blanchard Jerrold, the son of the writer Douglas Jerrold, who in 1869 commissioned him to produce a portrait of the city, resulting in the 180 engravings that were published in London: A Pilgrimage in 1872.
THE RETURNING ARMY.
Authors: N. SENN
Journal: JAMA (1898)

The war is over and the heroes who freed the Western Continent from Spanish despotism are returning home. The first war of invasion on our part has been a short, decisive one. Only four months have passed by since the Chief Executive issued the first call to arms, and more than we expected has been accomplished. The outside world, which has sneered too long at our fighting strength as a nation, has been convinced that it is dangerous to trifle with Americans in matters of war. In less than two months after war was declared we had more than two hundred thousand men in the field, eager and anxious to face the dangers of active warfare. Less than one-half of this army took part in the invasion. The enemy's navy was entirely destroyed; not a single ship that came within range of our guns escaped. The proud Spanish fleet is
Judicial functions of GMC should be abolished
Authors: O. O A Oni
Journal: BMJ (2001)

EDITOR—Attempts are afoot to turn the General Medical Council into an Alan Milburn quango; hence, it has become necessary for doctors to know what they would be deprived of as a consequence.

Currently, the GMC is like a court and is therefore not accountable to ministers or the public. It is a domestic tribunal with the sole purpose of allowing doctors to sit in judgment over other doctors. Therefore, although the Medical Act 1983 makes provision for non-doctors …
Psychosocial Status of Children With Diabetes in the First 2 Years After Diagnosis
Authors: Margaret Grey, Mary Emily Cameron, Terri H Lipman, Frances W Thurber
Journal: Diabetes Care (1995)

The purpose of this study was to determine the pattern of adjustment over time of a cohort of children with newly diagnosed diabetes compared with a cohort of peer-selected children without diabetes over the first 2 years after the diagnosis of insulin-dependent diabetes mellitus (IDDM).Children (n = 89 with IDDM, n = 53 without IDDM) ages 8-14 years were studied with the Children's Depression Inventory, State-Trait Anxiety Inventory for Children, Child and Adolescent Adjustment Profile, Self-Perception Profile for Children, and a general health scale. Initial data were collected within 6 weeks of the diagnosis of IDDM and at 3, 6, 12, and 24 months thereafter.There were no demographic differences between the two groups. Initially, children with diabetes were more depressed, more dependent, and more withdrawn than their peers. By 1 year postdiagnosis, there were no significant differences in psychosocial status between the two groups. By 2 years postdiagnosis, depression, dependency, and withdrawal were significantly higher in children with diabetes than in their peers without IDDM. Self-perceived competence remained similar between the two groups at all time points.After an initial period of adjustment, children with IDDM have equivalent psychosocial status to children without IDDM, but by 2 years after diagnosis, they have experienced twice the amount of depression and adjustment problems as their peers. Interventions should be aimed at this critical period between 1 and 2 years postdiagnosis.
GW25-e2351 The 24 hours variation of blood pressure may predict carotid plaque in patients with essential hypertension: a cross-sectional study
Authors: Liyuan Peng, Bin Yan, Quan Dong, Lu Sun, Pengtao Yang, Fengwei Zheng, Heanyee Ong, Gang Wang
Journal: Journal of the American College of Cardiology (2014)
Voluntary Medical Male Circumcision: An Introduction to the Cost, Impact, and Challenges of Accelerated Scaling Up
Authors: Catherine Hankins, Steven Forsythe, Emmanuel Njeuhmeli
Journal: PLoS Medicine (2011)

Catherine Hankins, Steven Forsythe, and Emmanuel Njeuhmeli provide an overview of the "Voluntary Medical Male Circumcision for HIV Prevention: The Cost, Impact, and Challenges of Accelerated Scale-Up in Southern and Eastern Africa" Collection, calling for leadership and vision to help halt the HIV epidemic.
Immunization Programs for Adults
Authors: Max Bader
Journal: JAMA (1977)

To the Editor.—  The points made by Hickman and Barness in their commentary Immunization Program for Adults (237:129, 1977) are well taken but deserve some amplification.  First, physicians considering administration of tetanus toxoid as part of wound prophylaxis would be well advised in most cases to use tetanusdiphtheria toxoids (adult). No tetanus booster is needed following most wounds where the last booster was given less than five years previously. Thus, since diphtheria toxoid alone is not generally available and most adults never receive any boosters unless they are confronted with this need after a wound, updating against diphtheria at that time is also in order and will not cause excessive reaction to the diphtheria component. Second, when an adult has never been immunized against diphtheria, physicians should regard the booster dose of adult diphtheria-tetanus toxoids as an integral part of the immunization series and establish a reminder system to get
Editorial: Modification of class III anti-arrhythmic activity in abnormal myocardium
Authors: S. M COBBE
Journal: Cardiovascular Research (1988)

Journal Article Editorial: Modification of class III anti-arrhythmic activity in abnormal myocardium Get access STUART M COBBE STUART M COBBE From the Department of Medical Cardiology, Royal Infirmary, Glasgow, Scotland Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 22, Issue 12, December 1988, Pages 847–854, https://doi.org/10.1093/cvr/22.12.847 Published: 01 December 1988
Mesenteric Infarction
Authors: Harold I. Miller, Seymour A. DiMare
Journal: New England Journal of Medicine (1958)

MESENTERIC infarction is a relatively infrequent disease comprising approximately 1 in every 1000 hospital admissions. The mortality rate remains high at about 80 per cent.1 The first successful resection for this disease was reported in 1895.2 Yet a collective review in 1954 was able to report only 154 cases in which survival followed resection.3 Embolectomy was first suggested by Ryvlin4 in 1943 and Klass5 in 1951, but the first successful one was recently reported by Shaw and Rutledge.6 Mesenteric vascular occlusion may be classified according to the primary event as follows: arterial (embolic or thrombotic); venous; or mixed. Embolism is . . .
Balloon injury of the rabbit aorta induces accumulation of vitronectin and vitronectin receptor (αvβ3), and hypercholesterolemia augments this effect
Authors: K.R. Coleman, M.H. Corjay, J.K. Stoltenborg, S.M. Diamond, G.A. Braden, D.C. Sane
Journal: Journal of the American College of Cardiology (1998)
The Twentieth Specialty
Authors: Leland B. Blanchard
Journal: JAMA (1970)

Elsewhere in this issue (p 1191) John Walsh, MD, president of the American Board of Family Practice, has outlined how this new specialty came into being. If family physicians are to be called specialists, they need to be distinguished somehow from traditional specialists. With all its other problems, this developing field does not need those of semantics. As medical knowledge continue to increase and skills to improve, the need for some physicians to limit themselves and develop depth of knowledge and skills in smaller and smaller segments of medicine seems self-evident. As this division of labor and fragmentation of the science of medicine continues, the increasing need for other physicians to develop breadth of knowledge and skills in all fields and aspects of medicine to coordinate this expanding medical care for the benefit of the public seems equally self-evident. Since consulting is their primary role, the former practitioners may be
Insulin-Sensitizing Effects of Telmisartan
Authors: Harrihar A. Pershadsingh, Theodore W. Kurtz
Journal: Diabetes Care (2004)

The angiotensin II type 1 receptor blocker (ARB) telmisartan was reported to activate the peroxisome proliferator-activated receptor-γ (PPARγ) in transactivation assays, whereas other ARBs, with the possible exception of irbesartan, did not (1). Telmisartan also induced adipogenesis and increased the expression of PPARγ target genes in preadipocyte fibroblasts (1), both of which are hallmark properties of PPARγ agonists.

We report a case of a 52-year-old man with hypertension, visceral obesity (BMI 34.4 kg/m2), and impaired glucose tolerance (pre-diabetes), in whom administration of telmisartan (80 mg/day) normalized blood pressure, improved insulin resistance, and reduced plasma triglycerides. During the 10 weeks after initiating telmisartan, …
THREE CASES OF MELAENA NEONATORUM SUCCESSFULLY TREATED BY THE INJECTION OF WHOLE BLOOD OR BLOOD SERUM
Authors: R. Hutchison
Journal: BMJ (1917)

BMTO"RvL_-mauve) about even the smallest axis cylinders.-This is t[ue to the neurokeratin contents of the youngest fibre.Two histological points are to be noted even in the youngest fibrils of adults or embryo; one is the cones, barbs, renflements biconigqules, or whatever they be called, and the other is the so-called vacuoles,-gonflements of imyelin moniliform appearance of tlle fibrils, due to the neurokeratin framework.Thev show so clearly with my neurokeratin stain that the photographs I amn preparing vill speak better than words.There is one fact that should be noted, however-that is, that stretching or compressing a nerve draws out tlhis neurokeratin support into cone-shaped form, leaving the point finely drawn out along tle axis cylinder, which it ensheaths, and the base toward the s'heath of Schwann, each cone being from 10 to 40, long, depending on the amount of stretch.The base appears more deeply stained-not so; it is merely that, being at the wider attachment, there is a greater amount of it stained at tlle point viewed; this mnasses the pigment.There are a number of interesting points that one can explain, and work is now in progress to put a correct interpretation on mnany long and acrimuoniotusly discussed questions.
Droxidopa, an oral norepinephrine precursor, improves hemodynamic and renal alterations of portal hypertensive rats
Authors: Mar Coll, Sarai Rodriguez, Imma Raurell, Nahia Ezkurdia, Astrid Brull, Salvador Augustin, Jaime Guardia, Rafael Esteban, María Martell, Joan Genescà
Journal: Hepatology (2012)

We aimed to evaluate the effects of droxidopa (an oral synthetic precursor of norepinephrine) on the hemodynamic and renal alterations of portal hypertensive rats. Sham, portal vein-ligated (PVL), and 4-week biliary duct-ligated (BDL) rats received a single oral dose of droxidopa (25-50 mg/kg) or vehicle and hemodynamic parameters were monitored for 2 hours. Two groups of BDL and cirrhotic rats induced by carbon tetrachloride (CCl4) were treated for 5 days with droxidopa (15 mg/kg, twice daily, orally); hemodynamic parameters and blood and urinary parameters were assessed. The droxidopa effect on the Rho kinase (RhoK) / protein kinase B (AKT) / endothelial nitric oxide synthase (eNOS) pathways was analyzed by western blot in superior mesenteric artery (SMA). The acute administration of droxidopa in PVL and BDL rats caused a significant and maintained increase in arterial pressure and mesenteric arterial resistance, with a significant decrease of mesenteric arterial and portal blood flow, without changing portal pressure and renal blood flow. Two-hour diuresis greatly increased. Carbidopa (DOPA decarboxylase inhibitor) blunted all effects of droxidopa. Chronic droxidopa therapy in BDL rats produced the same beneficial hemodynamic effects observed in the acute study, did not alter liver function parameters, and caused a 50% increase in 24-hour diuresis volume (7.4 ± 0.9 mL/100g in BDL vehicle versus 11.8 ± 2.5 mL/100g in BDL droxidopa; P = 0.01). Droxidopa-treated rats also showed a decreased ratio of p-eNOS/eNOS and p-AKT/AKT and increased activity of RhoK in SMA. The same chronic treatment in CCl4 rats caused similar hemodynamic effects and produced significant increases in diuresis volume and 24-hour natriuresis (0.08 ± 0.02 mmol/100g in CCl4 vehicle versus 0.23 ± 0.03 mmol/100g in CCl4 droxidopa; P = 0.014). Conclusion : Droxidopa might be an effective therapeutic agent for hemodynamic and renal alterations of liver cirrhosis and should be tested in cirrhosis patients.