tbuckley/cabot-search huggingface dataset:
Conformational changes in von Willebrand's factor protein: Effects on the binding of factor VIII‐coagulant
Authors: Roger E. Benson, Douglas W. Jones, W. Jean Dodds
Journal: American Journal of Hematology (1986)

Abstract The effects of conformational changes in purified canine von Willebrand's factor (VWF) were investigated to explore the relationship between its factor VIII‐related antigen (VIIIR:AG) and ristocetin cofactor (RCoF) properties and the factor VIII‐coagulant (VIII:C) binding site(s). Binding of VIII:C from canine von Willebrand's disease (VWD) plasma by VWF was used to measure the combining reaction of these proteins. The VWF was denatured to varying degrees by exposure to temperature and pH extremes, low ionic strength, and 6 M urea. Various treatments resulted in three types of change: elimination of RCoF, VIIIR:Ag, and VIII:C binding, removal of RCoF activity alone; or elimination of RCoF and retarded elution of VIIIR:Ag and VIII:C. As long as VIIIR:Ag reactivity was maintained, binding of VIII:C could be demonstrated; but in the absence of VIIIR:Ag, neither RCoF activity nor VIII:C binding remained. These results suggest that VIII:C binding and RCoF sites are separate on VWF and that interaction between VIII:C and VWF is possible even after significant structural changes occur in VWF. Furthermore, RCoF is more vulnerable to denaturation than the antigenic site. The spectrum of conformational changes that affect the properties of VWF may parallel the various recognized subtypes of VWD.
Systematic Reviews in Health Care
Authors: Lawrence Loo
Journal: Annals of Internal Medicine (2002)

Medical Writings: Book Notes1 October 2002Systematic Reviews in Health CareLawrence Loo, MDLawrence Loo, MDDivision of General Internal Medicine, Loma Linda University School of Medicine, Loma Linda, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-7-200210010-00035 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Glasziou P, Irwig L, Bain C, Colditz G. 148 pages. New York: Cambridge Univ Pr; 2001. $30.00. ISBN 0521799627. Order phone 914-937-9600.Field of medicine: Evidence-based medicine and medical literature review.Format: Softcover book.Audience: Clinicians, researchers, and reviewers (including those on editorial boards) who wish to sharpen their ability to read, write, and critique review articles.Purpose: To describe how to approach, gather and combine, synthesize, and present information for a systematic review.Content: The book is divided into two parts. The first part introduces the fundamental concepts of systematic reviews and ways to avoid common errors for each ... Author, Article, and Disclosure InformationAffiliations: Division of General Internal Medicine, Loma Linda University School of Medicine, Loma Linda, California. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 2002Volume 137, Issue 7Page: 630KeywordsEtiologyEvidence based medicineHealth careHealth information technologyInformation technologyLibrariesMedical risk factorsSoftware toolsSystematic reviews ePublished: 1 October 2002 Issue Published: 1 October 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
PHENOLPHTHALEIN AND AGAROL
Authors: Zachary Sagal
Journal: JAMA (1927)

<h3>To the Editor:</h3> —It is surprising how few in the medical profession, as well as among the laity, know of the high phenolphthalein content of one of the emulsions of liquid petrolatum marketed under the name of "Agarol." The impression gained from the advertising matter and the circulars supplied by the manufacturers of the preparation is that it represents merely a mixture of mineral oil and agar. The label on the bottle exhibits the words "mineral oil" and "agar agar" in large type, and the word "phenolphthalein" in minute letters. Little wonder that the latter ingredient is generally overlooked. Physicians advising its use, as well as patients using it, do not realize that they are being weaned away from the use of pills or tablets containing phenolphthalein as their active ingredient, to the use of this liquid, which contains phenolphthalein in considerable dosage. The composition of the preparation was reported
Abstract IA07: New functions for histone modifying enzymes
Authors: Sharon Y.R. Dent, Boyko Atanassov, Calley Hirsch, Evangelia Koutelou, John Latham
Journal: Cancer Research (2013)

Abstract Histone modifying enzymes are important creating and maintaining epigenetic programs that regulate cell identity and growth. Mutations or abnormal expression of these proteins are associated with multiple cancers. Our lab uses genetic approaches to define the full spectrum of functions for these enzymes. For example, we have created a series of mutations in the mouse Gcn5 gene in order to define the functions of this histone acetyltransferase (HAT) in a mammalian system. Deletion of Gcn5 led to early embryonic death and to telomere dysfunction. Biochemical studies revealed that depletion of Gcn5 or ubiquitin specific protease 22 (Usp22), which is another bona fide component of the Gcn5-containing SAGA-type complex, increases the turnover of two shelterin proteins, TRF1 and POT1a (Atanassov, 2009). Our studies provided the first indication that Gcn5 and mammalian SAGA influence telomere maintenance and the first demonstration that SAGA affects protein stability. We are now defining the role of Gcn5 and SAGA in maintenance of pluripotency in ES cells and ES cell differentiation. Our data indicate that Gcn5 is an important cofactor for both Myc and E2F family transcription factors. We are also identifying additional USP22 protein substrates and are defining USP22 functions during mouse development. We have also discovered unexpected functions for the Set1 lysine methyltransferase, which is highly homologous with the MLL protein, during mitosis. We found that Set1 methylates kinetochore proteins, such as Dam1, in yeast, and we have determined that H2Bub is required in trans for methylation of this protein. This work provides the first example of cross talk between a histone modification and a modification in a non-histone protein, defining a new mode of “chromatin signaling.” Zhang K, Lin W, Latham JA, Riefler GM, Schumacher JM, Chan C, Tatchell K, Hawke DH, Kobayashi R, Dent SY. The Set1 methyltransferase opposes Ipl1 aurora kinase functions in chromosome segregation. Cell 122(5):723-34, 9/2005. PMCID: PMC1794220 Atanassov BS, Evrard YA, Multani AS, Zhang Z, Tora L, Devys D, Chang S, Dent SY. Gcn5 and SAGA Regulate Shelterin Protein Turnover and Telomere Maintenance. Mol Cell 35(3):352-364, 8/2009. PMCID: PMC2749492. Atanassov BS, Dent SY. USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1. EMBO Rep 12(9):924-30, 9/2011. e-Pub 9/2011. PMCID: PMC3166460. Latham JA, Chosed RJ, Wang S, Dent SY. Chromatin signaling to kinetochores: Trans-regulation of Dam1 methylation by histone H2B ubiquitination. Cell 146(5):709-19, 9/2011. PMCID: PMC3168986. Citation Format: Sharon Y.R. Dent, Boyko Atanassov, Calley Hirsch, Evangelia Koutelou, John Latham. New functions for histone modifying enzymes. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr IA07.
Teriparatide Therapy for Alendronate-Associated Osteonecrosis of the Jaw
Authors: Ada Cheung, Ego Seeman
Journal: New England Journal of Medicine (2010)

To the Editor: An 88-year-old woman presented to our clinic with a 12-month history of pain, suppuration, and failed healing of a mandibular socket after tooth extraction, despite debridement and the administration of antibiotics. Computed tomographic imaging revealed necrosis of the left mandible consistent with the diagnosis of osteonecrosis of the jaw (Figure 1A and 1B). For 20 years, the patient had been taking prednisolone (at a dose of 5 mg per day) for the treatment of asthma. After a hip fracture 10 years earlier, she had begun taking 70 mg of alendronate per week, along with daily calcium carbonate (1500 mg) . . .
Trails of antiplatelet therapy
Authors: H Bounameaux, C Baigent, R Collin, R Peto, P Bell, P Sandercock
Journal: BMJ (1994)

Editor, - The impressive collaborative overview of antiplatelet therapy for prevention of venous thromboembolism1 raises several question which are of great practical relevance in daily practice. Firstly, this meta -analysis contradicts the recommendations given by consensus panels2 and also the general opinion of experts that aspirin has little or no effect on venous thrombosis or pulmonary embolism. Secondly, the authors studied 9000 randomised patients from 62 trials (only two published later than 1985); another systematic overview published five years ago found only five trials and 762 randomised patient and concluded …
Italy's austerity measures have led to delays in allocating research funds
Authors: F. Turone
Journal: BMJ (2015)

Applications for research funding submitted in response to a call issued in early 2012 by the Italian Medicines Agency (Agenzia Italiana per il Farmaco) are still to be decided, with several million euro waiting to be assigned and no solution in sight.

The issue was raised recently in a letter from 16 researchers to the top officials of the agency and the minister of health and in a written parliamentary question from Senator Nerina Dirindin, of the Democratic Party (which currently leads the government …
Characterization of cross‐reacting allergens in mango fruit
Authors: A. Paschke, H. Kinder, K. Zunker, M. Wigotzki, H. Steinhart, R. Weßbecher, I. Vieluf
Journal: Allergy (2001)

Allergic reactions to mango fruit have become increasingly important. A cross-reaction between mango fruit, various other foods, and respiratory allergens has been assumed but not investigated until now.The sera of nine patients were used to characterize cross-reacting allergens in mango fruits by EAST inhibition and immunoblot inhibition.EAST inhibition and immunoblot inhibition demonstrated that cross-reactions between mango fruits, mugwort pollen, birch pollen, celery, and carrot are based on allergens related to Bet v 1 and Art v 1, the major allergens of birch and mugwort pollen, respectively.
Abstract 4726: Virus-guided fluorescence imaging of intraperitoneal free gastric cancer cells as a potential clinical biomarker
Authors: Megumi Watanabe, Shunsuke Kagawa, Michihiro Ishida, Naoto Hori, Satoru Kikuchi, Shinji Kuroda, Hiroyuki Kishimoto, Masahiko Nishizaki, Hiroshi Tazawa, Toshiyoshi Fujiwara
Journal: Cancer Research (2014)

Abstract Peritoneal dissemination is a common pattern of metastasis in patients with gastric cancer, and associated with worse prognosis. Peritoneal lavage cytology during the operation is an important factor in predicting future development of peritoneal metastasis and determining the treatment strategy, but its sensitivity and specificity are unsatisfactory. TelomeScan is an adenovirus engineered to replicate and express GFP only in telomerase-activating tumor cells, so that we can easily detect viable cancer cells even among numerous normal cells. We hypothesized that TelomeScan might be applicable to detecting free cancer cells in peritoneal wash. Methods: Peritoneal washes were obtained from 42 gastric cancer patients during operation. The number of GFP-positive cells was determined for each sample and compared with cytology results and clinicopathological data Results: Clinical stage was ranged from IA to IV, and thirteen cases were diagnosed as class IV or class V by peritoneal lavage cytology. More than 10 GFP-positive cells were detected in 12 out of 42 cases, and these cases showed a worse prognosis when compared to the other 30 cases. Conclusion: We were able to detect gastric cancer cells as GFP-positive cells in peritoneal wash using TelomeScan. Furthermore, the presence of GFP-positive cells in peritoneal wash was associated with worse prognosis. These results suggest that number of cancer cells detected by TelomeScan in the peritoneal wash may have important clinical implication as prognostic and therapeutic biomarkers in gastric cancer. Citation Format: Megumi Watanabe, Shunsuke Kagawa, Michihiro Ishida, Naoto Hori, Satoru Kikuchi, Shinji Kuroda, Hiroyuki Kishimoto, Masahiko Nishizaki, Hiroshi Tazawa, Toshiyoshi Fujiwara. Virus-guided fluorescence imaging of intraperitoneal free gastric cancer cells as a potential clinical biomarker. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4726. doi:10.1158/1538-7445.AM2014-4726
Genetics of Adrenal Steroid 21-Hydroxylase Deficiency*
Authors: MARIA I. NEW, PHYLLIS W. SPEISER
Journal: Endocrine Reviews (1986)

Impairment of 21-hydroxylation is the most common enzymatic deficiency resulting in the syndrome of CAH, which may present either in the classical form in infants or in the nonclassical form in older individuals. Variable signs and symptoms of androgen excess are common to both types of the disorder, which are transmitted as autosomal recessive traits linked to HLA. Virilization begins in the second month of gestational life in classical 21-OHD, but postnatally in the nonclassical form. Salt wasting is a feature of the disease in a large number of classical patients; in the simple virilizing form aldosterone biosynthesis, a function of the adrenal zona glomerulosa, is intact. Additionally, no patient with nonclassical 21-OHD has been found to have salt wasting. Levels of precursor hormones are less markedly elevated in nonclassical 21-OHD, reflecting a less severe enzyme deficiency; coordinates of basal and stimulated 17-OHP are plotted on a nomogram to ascertain diagnostic category within a family. Confirmatory evidence of heterozygosity within the family of an affected proband is found by performing HLA typing. Specific linkage disequilibria exist for the classical and nonclassical forms of 21-OHD. Frequency of the classical disease is 1/5,000-1/15,000 in Caucasians, whereas the nonclassical disease is found in approximately 1/100 individuals in the Caucasian population, placing the latter disorder among the most common autosomal recessive disorders in man. A deletion of the active 21-hydroxylase gene has been detected in some classical patients; further investigations are in progress to elucidate the molecular genetics of this disease.
Carbamazepine in pregnancy
Authors: I. Nulman
Journal: BMJ (2010)

Has the best safety profile, and is therefore the drug of choice

Epilepsy is the most common neurological disorder seen in pregnant women. It often needs drug treatment, and it causes complications in about 0.25% of all pregnancies. Seizure control is the primary goal when treating a convulsive disorder. Epilepsy itself is not associated with an increased risk of major congenital malformations,1 although some risk cannot be excluded. All first line antiepileptic drugs, such as valproic acid, carbamazepine, and phenytoin, are associated with a twofold to threefold increase in rates of major congenital malformations compared with the general population. In the linked review of observational data (doi:10.1136/bmj.c6581), Jentink and colleagues assessed major congenital malformations associated with the use of carbamazepine in the first trimester of pregnancy⇓.2



Gustoimages/Science Photo Library

The benefits of seizure control during pregnancy should not be underestimated. For many pregnant women, discontinuing antiseizure drugs is not an option. The choice of drug is challenging to patients and doctors because of the conflict between the optimal treatment of the mother and the wellbeing of the fetus. Women should plan their pregnancy, receive evidence based …
LY303511 Enhances TRAIL Sensitivity of SHEP-1 Neuroblastoma Cells via Hydrogen Peroxide–Mediated Mitogen-Activated Protein Kinase Activation and Up-regulation of Death Receptors
Authors: Kirthan Shenoy, Yongfei Wu, Shazib Pervaiz
Journal: Cancer Research (2009)

We recently reported that LY294002 (LY29) and LY303511 (LY30) sensitized tumor cells to drug-induced apoptosis independent of the phosphoinositide 3-kinase/Akt pathway. Here, we investigated the mechanism of LY30-induced sensitization of human neuroblastoma cells to TRAIL-mediated apoptosis. We provide evidence that LY30-induced increase in intracellular H(2)O(2) up-regulates the expression of TRAIL receptors (DR4 and DR5) in SHEP-1 cells by activating mitogen-activated protein kinases, resulting in a significant amplification of TRAIL-mediated caspase-8 processing and activity, cytosolic translocation of cytochrome c, and cell death. Involvement of the death receptors was further confirmed by the ability of blocking antibodies against DR4 and/or DR5 to inhibit LY30-induced TRAIL sensitization. Pharmacologic inhibition of c-Jun NH(2) terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activation by SP600125 and PD98059, respectively, blocked LY30-induced increase in sensitization to TRAIL-mediated death. Finally, small interfering RNA-mediated gene silencing of JNK and ERK inhibited LY30-induced increase in surface expression of DR4 and DR5, respectively. These data show that JNK and ERK are two crucial players involved in H(2)O(2)-mediated increase in TRAIL sensitization of tumor cells upon exposure to LY30 and underscore a novel mode of action of this inactive analogue of LY29. Our findings could have implications for the use of LY30 and similar compounds for enhancing the apoptotic sensitivity of neuroblastoma cells that often become refractory to chemotherapy.
HIV Antibody Prevalence Data Derived From Study of Massachusetts Infants
Authors: Charles Marwick
Journal: JAMA (1987)

INVESTIGATORS at the Massachusetts Department of Health in Boston have opened a way to detecting the prevalence of antibody to the human immunodeficiency virus (HIV) in childbearing women. By extension, they have provided the first data on the true prevalence of the antibody in the US general population.  Their findings confirm the estimates of HIV seropositivity that have been made by the Centers for Disease Control (CDC) in Atlanta but which, of necessity, have been based on a number of assumptions. For example, it is assumed that the present trend in acquired immunodeficiency syndrome (AIDS) cases is unlikely to change from that reported over the past five years.  The Massachusetts group is headed by George Grady, MD. Its members point out that, since their study includes demographic data on the broad variations of HIV seroprevalence, it will enable those who advocate routine HIV-antibody screening (such as President Ronald Reagan) to
Coexistence of Sleep Apnea and Asthma Resulting in Severe Sleep Hypoxemia
Authors: David W. Hudgel
Journal: JAMA (1979)

ALTHOUGH significant hypoxemia may be present during status asthmaticus,<sup>1</sup>severe hypoxemia is unusual in chronic bronchial asthma.<sup>2</sup>We report the case of a patient with chronic bronchial asthma who had mild hypoxemia while awake, but the patient was unusual in that he had erythrocytosis. During sleep he had severe hypoxemia that was primarily due to obstructive apnea. A tracheostomy was required for effective treatment of the apnea and hypoxemia. <h3>Report of a Case</h3> A 66-year-old man from Detroit was referred to National Jewish Hospital and Research Center for evaluation and treatment of asthma. The patient had frequent episodes of intermittent dyspnea accompanied by wheezing for 2 1/2 years before admission. He had never been a cigarette smoker and produced minimal sputum. The patient reported more dyspnea during sleeping hours and awakening almost hourly. His spouse related a history of his loud snoring accompanied by fitful sleep, which had
Mindfulness-Based Stress Reduction as an Adjunct to Outpatient Psychotherapy
Authors: Myra Weiss, Johanna W. Nordlie, Eric P. Siegel
Journal: Psychotherapy and Psychosomatics (2005)

Research on Mindfulness-Based Stress Reduction (MBSR) has supported the utility of the technique in a number of clinical settings. This study explored whether MBSR, used as an adjunct to individual psychotherapy, would result in more rapid alleviation of symptoms, increased achievement of therapeutic goals, and a decrease in number of therapy sessions sought by clients.A group undergoing psychotherapy coupled with training in MBSR was compared with a group undergoing psychotherapy alone.At the conclusion of MBSR training, the groups showed a comparable significant decrease in psychological distress. However, the MBSR group's gains on a novel measure of goal achievement were significantly greater than those of the comparison group. In addition, the MBSR group terminated therapy at a significantly greater rate than the comparison group.The effects of introducing MBSR early in psychotherapy, as well as its effect on self-directed goal attainment in non-psychotherapy contexts, deserve further attention.
Sputum Cysteinyl Leukotrienes Increase 24 Hours after Allergen Inhalation in Atopic Asthmatics
Authors: ALISON J. MACFARLANE, RYSZARD DWORSKI, JAMES R. SHELLER, IAN D. PAVORD, A. BARRY KAY, NEIL C. BARNES
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We have used the relatively noninvasive technique of induced sputum to measure allergen-induced changes in the concentration of eicosanoid mediators in bronchial secretions from atopic asthmatics. Sputum induction was performed before and 24 h after inhalational allergen challenge in 14 atopic asthmatics who developed a late asthmatic reaction (LAR). Differential cell counts were made on sputum cytospins and eicosanoid (cysteinyl leukotrienes [cys LTs], prostaglandin D2 [PGD2], and PGE2) concentrations were measured in the sputum supernatants. The percentage of eosinophils at baseline correlated with the concentration of cys LTs (r = 0.84, p < 0.001) but not prostanoid mediators. Allergen challenge produced a significant increase in the concentration of sputum cys LTs from 3.45 ng/ml sputum to 11.95 ng/ml (p = 0.002), which correlated with the increase in sputum eosinophils (r = 0.55, p < 0.05). There were no significant changes in PGD2 or PGE2 concentrations in sputum supernatants in response to challenge. Thus, the noninvasive technique of induced sputum has been used to demonstrate increased cys LTs, but not prostanoids associated with LAR after allergen challenge. The correlation between eosinophil numbers and cys LT concentrations at baseline values and 24 h after allergen challenge is consistent with these cells being a principal source of cys LTs within the airways at these time points.