tbuckley/cabot-search huggingface dataset:
Abstract 3904: uPAR-regulated nuclear translocation of hand-1 mediates vascular radiosensitivity in medulloblastoma tumors.
Authors: Swapna Asuthkar, Kiran Kumar Velpula, Arun Kumar Nalla, Venkateswara Rao Gogineni, Venkata Ramesh Dasari, Bharathi Gorantla, Jasti S. Rao
Journal: Cancer Research (2013)

Abstract Urokinase-type plasminogen activator (uPAR) is overexpressed in the tumor-stromal invasive microenvironment in many human cancers including medulloblastoma. The role of uPAR in tumor progression and angiogenesis has been well characterized. Most recently, in medulloblastoma cells, we showed that ionizing radiation (IR)-induced uPAR is a potent activator of cancer stem cell (CSC)-like properties and is associated with various transcription factors that are involved during embryonic development and cancer. In this study, we show that the uPAR protein is a cytoplasmic sequestration factor for a novel basic helix-loop-helix (bHLH) transcription factor, Hand-1. The Hand-1 protein plays an essential role in differentiation of trophoblast giant cells and cardiac morphogenesis, and yet its precise cellular function and its contributions to cancer remain mostly unknown. In the present study, we observed that Hand-1 protein is upregulated in uPAR shRNA-treated medulloblastoma cells and accompanies sustained cell growth and angiogenesis. Furthermore, IR-induced uPAR overexpression negatively regulates Hand-1 activity and results in the stabilization of angiogenesis promoting molecules, such as HIF-1 alpha. Finally, uPAR overexpression and its association with Hand-1 after IR treatment indicate that uPAR is capable of regulating Hand-1 and that uPAR has a role in the process of IR-induced tumor angiogenesis. Citation Format: Swapna Asuthkar, Kiran Kumar Velpula, Arun Kumar Nalla, Venkateswara Rao Gogineni, Venkata Ramesh Dasari, Bharathi Gorantla, Jasti S. Rao. uPAR-regulated nuclear translocation of hand-1 mediates vascular radiosensitivity in medulloblastoma tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3904. doi:10.1158/1538-7445.AM2013-3904
81 A ROLE FOR ANTICOAGULATION IN FIBROGENESIS: SUPPRESSION OF HUMAN HEPATIC STELLATE CELL CONTRACTILITY AND LIVER FIBROSIS IN VITRO AND VIVO
Authors: A. Dhar, Q.M. Anstee, F. Sadiq, A. Levene, J. Cobbold, G. Petts, S. Taylor-Robinson, R. Goldin, M.R. Thursz
Journal: Journal of Hepatology (2012)
Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor
Authors: Anne F. Riddell, Keith Gomez, Carolyn M. Millar, Gillian Mellars, Saher Gill, Simon A. Brown, Megan Sutherland, Mike A. Laffan, Thomas A. J. McKinnon
Journal: Blood (2009)
Proteolytic inactivation of plasma C1- inhibitor in sepsis.
Authors: J H Nuijens, A J Eerenberg-Belmer, C C Huijbregts, W O Schreuder, R J Felt-Bersma, J J Abbink, L G Thijs, C E Hack
Journal: Journal of Clinical Investigation (1989)

Activation of both the complement system and the contact system of intrinsic coagulation is implicated in the pathophysiology of sepsis. Because C1 inhibitor (C1-Inh) regulates the activation of both cascade systems, we studied the characteristics of plasma C1-Inh in 48 patients with severe sepsis on admission to the Intensive Care Unit at the Free University of Amsterdam. The ratio between the level of functional and antigenic C1-Inh (functional index) was significantly reduced in the patients with sepsis compared with healthy volunteers (P = 0.004). The assessment of modified (cleaved), inactive C1-Inh (iC1-Inh), and complexed forms of C1-Inh (nonfunctional C1-Inh species) revealed that the reduced functional index was mainly due to the presence of iC1-Inh. On SDS-PAGE, iC1-Inh species migrated with a lower apparent molecular weight (Mr 98,000, 91,000, and 86,000) than native C1-Inh (Mr 110,000). Elevated iC1-Inh levels (greater than or equal to 0.13 microM) were found in 81% of all patients, sometimes up to 1.6 microM. Levels of iC1-Inh on admission appeared to be of prognostic value: iC1-Inh was higher in 27 patients who died than in 21 patients who survived (P = 0.003). The mortality in 15 patients with iC1-Inh levels up to 0.2 microM was 27%, but in 12 patients with plasma iC1-Inh exceeding 0.44 microM, the mortality was 83%. The overall mortality in the patients with sepsis was 56%. We propose that the cleavage of C1-Inh in patients with sepsis reflects processes that play a major role in the development of fatal complications during sepsis.
Reviews, Notes, and Listings: Nephrology: Oxford Textbook of Clinical Nephrology
Authors: Gail Morrison
Journal: Annals of Internal Medicine (1993)

Literature of Medicine15 August 1993Reviews, Notes, and Listings: Nephrology: Oxford Textbook of Clinical NephrologyGail MorrisonGail MorrisonHospital of the University of Pennsylvania, Philadelphia, PA 19104.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-4-199308150-00043 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Oxford Textbook of Clinical NephrologyStewart Cameron, Alex M. Davision, Jean-Pierre Grunfeld, David Kerr, and Eberhard Ritz; eds. 2348 pages. Oxford: Oxford University Press; 1992. $295.00.During the last 15 years, an explosion of knowledge has occurred within the field of nephrology. Several reasons can account for this: The kidney, because of the development of highly sensitive analytic methodology, can now be studied at the tubular and cellular level; immunologic mechanisms underlying the pathogenesis of renal disease were identified using the electron microscopic and immunofluorescent techniques on kidney tissue; and the kidney and its role as an endocrine organ was ... Author, Article, and Disclosure InformationAffiliations: Hospital of the University of Pennsylvania, Philadelphia, PA 19104. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1993Volume 119, Issue 4Page: 351-352KeywordsBiopsyKidneysMolecular biologyNephritisNephrologyPathogenesisPopulation statisticsRenal diseasesRenal failureSystemic diseases ePublished: 15 August 2000 Issue Published: 15 August 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cilostazol Has Beneficial Effects in Treatment of Intermittent Claudication
Authors: David L. Dawson, Bruce S. Cutler, Mark H. Meissner, D. Eugene Strandness
Journal: Circulation (1998)

Background —Cilostazol is a new phosphodiesterase inhibitor that suppresses platelet aggregation and also acts as a direct arterial vasodilator. This prospective, randomized, placebo-controlled, parallel-group clinical trial evaluated the efficacy of cilostazol for treatment of stable, moderately severe intermittent claudication. Methods and Results —Study inclusion criteria included age ≥40 years, initial claudication distance (ICD) on treadmill (12.5% incline, 3.2 km/h) between 30 and 200 m, and confirmation of diagnosis of chronic lower-extremity arterial occlusive disease. After stabilization and single-blind placebo lead-in, 81 subjects (62 male, 19 female) from 3 centers were randomized unequally (2:1) to 12 weeks of treatment with cilostazol 100 mg PO BID or placebo. Primary outcome measures included ICD and maximum distance walked (absolute claudication distance, or ACD). Secondary outcome measures included ankle pressures, subjective assessments of benefit by patients and physicians, and safety. Treatment and control groups were similar with respect to age, severity of symptoms, ankle pressures, and smoking status. Statistical analyses used intention-to-treat analyses for each of 77 subjects who had ≥1 treadmill test after initiation of therapy. Comparisons between groups were based on logarithms of ratios of ICD and ACD changes from baseline using ANOVA test at last treatment visit. The estimated treatment effect showed a 35% increase in ICD ( P &lt;0.01) and a 41% increase in ACD ( P &lt;0.01). There was no significant change in resting or postexercise ankle/brachial indexes. Patients’ and physicians’ subjective assessments corroborated the measured improvements in walking performance observed in the cilostazol-treated group. Conclusions —Cilostazol improved walking distances, significantly increasing ICD and ACD. The data suggest cilostazol is safe and well tolerated for the treatment of intermittent claudication.
Stimulation of alpha 1 (I) procollagen gene expression in NIH-3T3 cells by the human T cell leukemia virus type 1 (HTLV-1) Tax gene.
Authors: E Muñoz, D Suri, S Amini, K Khalili, S A Jiménez
Journal: Journal of Clinical Investigation (1995)

The mechanisms that regulate the expression of genes encoding extracellular matrix proteins in fibroblasts and other mesenchymal cells have remained elusive. Studies from several laboratories have indicated that Tax, a trans-regulatory protein from the human T cell leukemia virus type I not only augments viral gene expression but also triggers the expression of various cellular genes. Here, we examined the hypothesis that the expression of collagen genes may also be modulated by Tax. NIH-3T3 cells were simultaneously transfected with a Tax expressor plasmid and a chimeric construct containing regulatory sequences (-804 to +42 bp) of the alpha 1(I) procollagen gene (COL1A1) promoter. The results indicated that the promoter activity of the -804 to bp COL1A1 fragment increased up to 12-fold in cells expressing Tax. Deletion analysis revealed that the region of COL1A1 encompassing nucleotides -174 to -84 contained the Tax-responsive elements. A gene segment encompassing nucleotides -187 to -67, which contained this region, proved sufficient to confer Tax inducibility (2.5-fold) to a herpes simplex virus thymidine kinase promoter. Stably transfected NIH-3T3 cell clones that constitutively produce Tax displayed elevated levels of alpha 1(I) procollagen and fibronectin transcripts and increased production and accelerated processing of type I procollagen. These findings suggest that retroviral proteins may be involved in the pathogenesis of idiopathic diseases accompanied by collagen overproduction.
Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice
Authors: Chang-yun Hu, Daniel Rodriguez-Pinto, Wei Du, Anupama Ahuja, Octavian Henegariu, F. Susan Wong, Mark J. Shlomchik, Li Wen
Journal: Journal of Clinical Investigation (2007)

The precise roles of B cells in promoting the pathogenesis of type 1 diabetes remain undefined. Here, we demonstrate that B cell depletion in mice can prevent or delay diabetes, reverse diabetes after frank hyperglycemia, and lead to the development of cells that suppress disease. To determine the efficacy and potential mechanism of therapeutic B cell depletion, we generated a transgenic NOD mouse expressing human CD20 (hCD20) on B cells. A single cycle of treatment with an antibody specific for hCD20 temporarily depleted B cells and significantly delayed and/or reduced the onset of diabetes. Furthermore, disease established to the point of clinical hyperglycemia could be reversed in over one-third of diabetic mice. Why B cell depletion is therapeutic for a variety of autoimmune diseases is unclear, although effects on antibodies, cytokines, and antigen presentation to T cells are thought to be important. In B cell–depleted NOD mice, we identified what we believe is a novel mechanism by which B cell depletion may lead to long-term remission through expansion of Tregs and regulatory B cells. Our results demonstrate clinical efficacy even in established disease and identify mechanisms for therapeutic action that will guide design and evaluation of parallel studies in patients.
Altered processing of sensory stimuli in patients with migraine
Authors: Marina de Tommaso, Anna Ambrosini, Filippo Brighina, Gianluca Coppola, Armando Perrotta, Francesco Pierelli, Giorgio Sandrini, Massimiliano Valeriani, Daniele Marinazzo, Sebastiano Stramaglia, Jean Schoenen
Journal: Nature Reviews Neurology (2014)
Evidence for motor neuropathy and reduced filling of the rectum in chronic intractable constipation.
Authors: D J Waldron, D Kumar, R I Hallan, D L Wingate, N S Williams
Journal: Gut (1990)

Subtotal colectomy with ileorectal anastomosis is now frequently offered to patients with slow transit constipation who have severe symptoms and no response to more conventional medical treatment. If this operation is to be successful, the underlying problem should be delay in the progress of contents through the colon but no mechanical or functional obstruction in the small bowel or rectum. We have used a recently described technique of prolonged ambulant manometry and electromyography to investigate anorectal function in these patients. Pressure data were collected using a 2 mm diameter intrarectal probe carrying microtransducers, and external anal sphincter activity was assessed by a pair of silver-silver chloride surface electrodes. Fourteen control subjects and eight patients with colonic inertia were studied. Sampling reflexes, indicative of rectal filling, occurred at mean (SEM) rates of 7.4 (2.0)/hour in controls but were significantly reduced in patients (2.4 (0.3)/hour (p less than 0.01]. Recurrent rectal motor complexes were seen to occur in both groups at intervals of 76 (1.8) minutes in controls and 64.9 (7.2) minutes in patients (p less than 0.1), and with amplitudes of 42.4 (2.1) mmHg and 9.2 (0.7) mmHg (p less than 0.001), respectively. External sphincter electromyographic spike activity did not differ between groups. Our results support the concept of reduced transit of faeces to the rectum from the colon over a 24 hour period in slow transit constipation and suggest that a motor neuropathy may also be present in the rectum.
Blockade of Late-phase Airway Responses and Airway Hyperresponsiveness in Allergic Sheep with a Small-molecule Peptide Inhibitor of VLA-4
Authors: WILLIAM M. ABRAHAM, ASHFAQ AHMED, MAREK W. SIELCZAK, MASAHIRO NARITA, THOMAS ARRHENIUS, MARIANO J. ELICES
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The leukocyte integrin very late antigen-4 (VLA-4) ( α4β1, CD49d/CD29) is an adhesion receptor predominantly expressed on lymphocytes, monocytes, and eosinophils, but not on neutrophils. Recent studies with monoclonal antibodies against VLA-4 suggest that antigen-induced late responses and airway hyperresponsiveness (AHR) may depend on the recruitment and/or activation of VLA-4-expressing leukocytes. To further test this hypothesis, we administered by aerosol either a potent small-molecule inhibitor of VLA-4, which prevents VLA-4-mediated binding to fibronectin (CS-1 ligand mimic), or an inactive control (30 mg twice daily for 3 d, and on the fourth day 0.5 h before and 4 h after antigen challenge) to six sheep with airway hypersensitivity to Ascaris suum antigen. Treatment with the small-molecule VLA-4 inhibitor resulted in a significant decrease in the early antigen-induced bronchial response (40%, p < 0.05), and almost complete blockade of the late-phase airway response (88%, p < 0.05). Moreover, at 24 h after antigen challenge, AHR to inhaled carbachol was not observed when the animals were dosed with the small-molecule VLA-4 inhibitor. In accord with protection against the functional abnormalities associated with antigen challenge, analysis of biopsy specimens taken 24 h after challenge indicated that the total numbers of VLA-4-positive cells (lymphocytes, eosinophils, and metachromatic-staining cells) in the group treated with the VLA-4 inhibitor did not increase, whereas these cells increased in the control group. The active agent, but not the inactive control, significantly blocked macrophage adherence to fibronectin (FN), indicating that the CS-1 ligand interfered with VLA-4-mediated adhesion in sheep cells. These results support our previous findings with a monoclonal antibody to VLA-4, and demonstrate that a small-molecule VLA-4 inhibitor, when given by aerosol, has a protective effect against antigen-induced late responses and AHR in allergic sheep.
Urinary Tamponade Due to a Tampon
Authors: Richard Milstein
Journal: JAMA (1977)

To the Editor.—  A myriad of foreign bodies have been recovered from the bladder that have either been inserted intentionally or inadvertently, and every urologist has his own tale to tell. Considering the number of women who insert intravaginal tampons during their menstrual cycle, it is surprising that more cases similar to the following have not been reported.  Report of a Case.—  A 21-year-old female college student was admitted in acute urinary retention. Several hours previously she had inserted a tampon into what she believed to be the vagina. On examination, two strings were noted to be protruding through the urethral meatus. In addition, there was a very pronounced hymenal ring compatible with a virginal state.  The patient was taken to the operating room and, under general anesthesia, cystoscopy was performed. Two strings lay along the course of the urethra and a large, expanded tampon was seen within the bladder.
THE HOSPITAL PROBLEM
Authors: S. Raw
Journal: BMJ (1921)

All workers in chemical pathology will be greatly in- debted to Professor CAVAZZANI for his excellent little book on the proteins of the urine.9The first two chapters are devoted to a qualitative dlescription of the proteins found in the urine.This is followed by an excellent account of all the latest methods for the quantitative estimnation of the various urinary proteins, and fe1ll justice is done to the pathological implications of the subject.A very useful analytical chart is appended.The bibliography is excep- tionally complete, and the monograph will save much time a-nd trouble to research wvorkers.
Heinz-Body Anemias
Authors: Thomas F. Necheles, Donald M. Allen
Journal: New England Journal of Medicine (1969)

THE "Heinz-body anemias" are a group of hemolytic syndromes of diverse etiology with a common morphologic characteristic, first described by Heinz,1 of one or more inclusion bodies within affected red cells (Fig. 1). Geubz bodies can be distinguished from other erythrocyte inclusions in that they can be visualized by phase-contrast microscopy, electron microscopy or light microscopy using supravital stains such as crystal violet. They are not stained with the useual Romanowsky dyes (such as Wright's stain) or with Prussian blue or nuclear dyes.The nature of one form of the Heinz body was elucidated by Jandl and his co-workers,2 who . . .
The limits to health promotion
Authors: N C H Stott, P Kinnersley, S Rollnick
Journal: BMJ (1994)

Everybody knows that prevention is better than cure, but the opposite, equally attractive, principle of paying tomorrow for what you can have today is an efficient way to use your resources: health economists call it “discounting.”1 Discounting is efficient because resources usually devalue over time, and numerous unexpected events are likely to overtake the person who delays gratification. To “eat, drink, and be merry for tomorrow we die” is a discounting approach to life. This is a challenge to the health promotion movement, particularly in relation to those in their teens and 20s, for whom tommorrow is a long way off. Health promotion has, of course, been achieved through traditional public health measures - for example, clean water and air and manipulation of the population2,3 - but success in local communities and with individuals is more controversial when people's choices are an important factor. Indeed, the limits to health promotion lie in the paradox that “a measure which brings large benefits to the community offers little to the participating individual.”2

Health is not a unidimensional concept, and many research workers have found that personal concepts of health vary according to context.*RF 4-7* Energised, health seeking people or families8 remain a minority in our society because most people regard health as a free asset to be used or enjoyed.*RF 5-9* Health can certainly be viewed as a resource that will devalue through aging and accidents. Most people struggle to modify their …
Confessions of a drug rep
Authors: Jeanne Lenzer
Journal: BMJ (2005)

A forthcoming movie claims to spill the beans on Big Pharma 

Think big. Think money. Think drugs. And then think of all the sly, silly, ethically impaired things that people will do to sell drugs, and you'll have a taste of Kathleen Slattery-Moschkau's film, Side Effects .

Slattery-Moschkau (pronounced Moscow, “like the city”) sold drugs for a living for Bristol-Myers Squibb and Johnson & Johnson, until she found it increasingly difficult to “look myself in the mirror,” and left her job after 10 years in the industry.

An aspiring screenwriter since her college years, Slattery-Moschkau, wrote, directed, and produced Side Effects , a satirical film about the dilemma of Karly Hert (Katherine Heigl), a drug representative torn between her conscience and some really good perks. Hert's company plans to roll out “the biggest drug launch of the 21st century” for its new antidepressant, Vivexx, which they enthusiastically promote as “absolutely the most efficacious drug your patients can use!” while cheerfully predicting that “Vivexx will make Prozac look like penny candy.”

Hert, who suffers pangs of conscience about some of the promotional techniques encouraged by her managers, launches a …
Clinical Experience with a Topical Light Filter
Authors: Ramon M. Fusaro, Walter J. Runge
Journal: JAMA (1962)

FOR THE PAST 2 YEARS we have been clinically evaluating a new topical agent which produces a light filter in the skin. This filter has the following advantages and characteristics: It absorbs 95% of the total ultraviolet (UV) and 20% of the infrared radiation reaching the skin. It is chemically bound to the skin; therefore, it can not be washed off and it need be renewed only every day or two to give protection from light in the majority of sunlight sensitive patients. Since the filter does not completely block out all UV radiation, the skin can acquire a natural tan but at a slower rate than normal. It is cosmetically acceptable in that it produces a natural brown color in the skin as a result of the chemical reaction between the application material and the keratin. The agent can be applied to the skin in a grease base, a
Suppository Treatment of Haemorrhoids
Authors: V. Goldman
Journal: BMJ (1967)

IBrr 113 that there is a good case for the nutritional origin of these megaloblastic anaemias.The high incidence of pregnancy megaloblastic anaemias in our district, 272 over the same 71-month period, would also support the mainly dietary origin of folate deficiency megaloblastic anaemias.While in some areas it holds true that per- nicious anaemia is the predominant megalo- blastic anaemia in the elderly, this does not appear to be the case in our patient material.This does not subtract from the import- ance of the recommendation contained in the last sentence of your leading article, but underlines at the same time the necessity of an exact diagnosis of the deficiency involved in megaloblastic anaemia in any age groupeven in the elderly.-Weare, etc.,
Ulceration of the cornea in rheumatoid arthritis.
Authors: M I Jayson, D L Easty
Journal: Annals of the Rheumatic Diseases (1977)

Five patients with melting of the cornea in association with rheumatoid arthritis are described. The arthritis was often inactive and without systemic manifestations, in contrast to that seen in association with scleritis. In 3 there was evidence of reduced tear formation, but in none was tear production absent. In 3 patients the lesions healed during treatment with azathioprine or penicillamine.