tbuckley/cabot-search huggingface dataset:
MUC1 Oncoprotein Blocks Glycogen Synthase Kinase 3β–Mediated Phosphorylation and Degradation of β-Catenin
Authors: Lei Huang, Dongshu Chen, Derek Liu, Li Yin, Surender Kharbanda, Donald Kufe
Journal: Cancer Research (2005)

Abstract Dysregulation of β-catenin is of importance to the development of diverse human malignancies. The MUC1 oncoprotein is aberrantly overexpressed by most human carcinomas and associates with β-catenin. However, the functional significance of the MUC1-β-catenin interaction is not known. Here, we show that MUC1 increases β-catenin levels in the cytoplasm and nucleus of carcinoma cells. Previous studies have shown that glycogen synthase kinase 3β (GSK3β) phosphorylates β-catenin and thereby targets it for proteosomal degradation. Consistent with the up-regulation of β-catenin levels, our results show that MUC1 blocks GSK3β-mediated phosphorylation and degradation of β-catenin. To further define the interaction between MUC1 and β-catenin, we identified a serine-rich motif (SRM) in the MUC1 cytoplasmic domain that binds directly to β-catenin Armadillo repeats. Mutation of the SRM attenuated binding of MUC1 to β-catenin and MUC1-mediated inhibition of β-catenin degradation. Importantly, disruption of the MUC1-β-catenin interaction with the SRM mutant also attenuated MUC1-induced anchorage-dependent and -independent growth and delayed MUC1-mediated tumorigenicity. These findings indicate that MUC1 promotes transformation, at least in part, by blocking GSK3β-mediated phosphorylation and thereby degradation of β-catenin.
T‐Cell large granular lymphocytic leukemia following orthotopic liver transplantation
Authors: O. Feher, D. Barilla, J. Locker, D. Oliveri, M. Melhem, A. Winkelstein
Journal: American Journal of Hematology (1995)

Abstract Aggressive T‐cell neoplasms are an infrequent complication of allogeneic organ and bone marrow transplantation. To date, chronic T‐cell lymphoproliferative malignancies have not been described. The present case documents the occurrence of a T‐cell large granular lymphocytic leukemia (T‐LGL) in a patient following orthotopic liver transplantation. Genotype studies showed a clonal T‐cell receptor α‐chain gene rearrangement. A unique feature was the detection of a specific chromosomal deletion at 1p32 involving the tal‐1 gene, an abnormality previously described only in aggressive T‐cell neoplasms. © 1995 Wiley‐Liss, Inc.
The cutaneous barrier to salts and water in psoriasis and in normal skin
Authors: KATHERINE GRICE, H. SATTAR, HARVEY BAKER
Journal: British Journal of Dermatology (1973)

A study has been made of the transepidermal water loss and its sodium and potassium content in normal and psoriatic skin. The results show a preservation of the electrolyte barrier in active psoriasis despite serious impairment of the water barrier.
ACCURACY AND REPRODUCIBILITY OF CONTRAST ENHANCED AND NON-ENHANCED COMPUTED TOMOGRAPHY FOR PREDICTING THE ANGIOGRAPHIC DEPLOYMENT ANGLE IN TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR)
Authors: Catherine N. Dao, Theodore Blake, David Liang, Michael P. Fischbein, Alan Yeung, William Fearon, D. Craig Miller, Dominik Fleischmann
Journal: Journal of the American College of Cardiology (2012)
Risk of Nonmelanoma Skin Cancer in Patients With Inflammatory Bowel Disease Who Use Thiopurines Is Not Increased
Authors: Fiona D.M. van Schaik, Martijn G.H. van Oijen, Hugo M. Smeets, Geert J.M.G. van der Heijden, Peter D. Siersema, Bas Oldenburg
Journal: Clinical Gastroenterology and Hepatology (2011)
Lessons from the Ashya King case
Authors: A. O'Brien, D. K. Sokol
Journal: BMJ (2014)

Clinicians must try to reduce the risk of misunderstandings

On 28 August 2014 the parents of 5 year old Ashya King took him from Southampton General Hospital and boarded a ferry to France. He had been recovering from the removal of a medulloblastoma, a high grade paediatric tumour.

Ashya’s parents and doctors disagreed over his treatment. The parents sought proton beam therapy, arguing that it was less harmful than conventional radiotherapy.1 Peter Wilson, the lead paediatrician at the hospital, has since commented, “For this particular tumour, the reason why the proton beam was not deemed to be of any benefit is because you have to irradiate most of the brain and spine anyway.”2 Proton beam therapy is not routinely provided on the NHS in England, although a small budget exists to take children abroad for treatment.

If a child lacks competence to make treatment decisions, the responsibility falls to the child’s parents. Yet, the parents’ right is not absolute. Where their instructions seem to conflict with the child’s best interests, the doctors must seek the court’s authority to override them, save for grave emergencies. A court can invoke its inherent jurisdiction under section 8 of the Children Act 1989 to make “specific issue orders” or “prohibited steps orders.” …
Human and animal health: strengthening the link: Methodological concerns about animal facilitated therapy with dolphins
Authors: Biju Basil, Maju Mathews
Journal: BMJ (2005)

Methodological concerns about animal facilitated therapy with dolphinsEditor-We have the following concerns with Antonioli and Reveley's study of animal facilitated depression with dolphins in the treatment of depression. 1 The study was small (30 patients), only 13 people from the animal care programme and 12 from the outdoor nature programme completing the study.The authors used a conservative measure to estimate the number of patients required for this study, and even then fell short by 17%.Single women predominated in both arms.It is difficult to fathom how clinical raters can be blinded to the treatment hypothesis.The authors did not mention the ethnic group of the participants.Only people who could go to Honduras were able to take part in this study.Most people with mild depression will not be able to take a three week holiday.The findings are not generalisable as most people would not be able to afford to go to such a location and swimming and snorkeling are not necessarily favourite pastimes.There may be a vacation bias.If the study group sponsored the three week trip to Honduras we suspect that a free three week trip to a seaside location in Latin America would in itself be a powerful antidepressant.There may be a disappointment bias.If the control group were aware of the potential to be in a group where they could interact with dolphins for two weeks before they reached Honduras, they could be disappointed in missing out.People with depression perceive disappointment more intensely.The study could have been done in a more natural and plausible setting with common pets such as dogs or cats for a fraction of the cost.
ACUTE ACTINOMYCOSIS OF THE PAROTID GLAND
Authors: E. D. Telford
Journal: BMJ (1915)

9, I9I 5 53 KRDIA JORA)-CT tZ9 3. The presence of tumours on the soles of the feet-an un zommon situation.4. Thle presence of the three types of pigmentation.5.The rapid increase in the size and number of tumours after operation.REFE3RENCES
P65 MUTATION SPECTRUM ASSOCIATED WITH THE PROGRESSION OF HBV-RELATED HEPATOCELLULAR CARCINOMA
Authors: H.G. Woo, S.S. Kim, H.W. Cho, S.M. Kwon, H.J. Cho, S.J. Ahn, S.W. Cho, J.Y. Cheong
Journal: Journal of Hepatology (2014)
A Substitute for Jogging as Exercise
Authors: John M. Trapnell
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Dr. Waldo E. Harris and his team are to be congratulated on their careful study and concise report, "Jogging: An Adult Exercise Program" (<b>201</b>:759, 1967). Unfortunately, by the fourth decade many of us have become relatively chair-bound and need some type of easily available physical activity to stimulate the circulation and, incidentally, burn up calories. I'm sure it would be pleasant to jog-walk around the University of Oregon track in Portland during the spring and fall. But what about jogging in the winter or summer, especially if one lives in Nome or New Orleans? Furthermore, social acceptance of this type of activity in some urban areas is highly questionable. Consequently, I would like to suggest an alternate type of moderate exercise which could be performed year-round and without any question as to acceptability. Requiring little skill and minimal equipment,<i>jumping "skipping" rope</i>should be a satisfactory
Replacing acid α-glucosidase in Pompe disease: recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers
Authors: Nina Raben, Tokiko Fukuda, Abigail L. Gilbert, Deborah de Jong, Beth L. Thurberg, Robert J. Mattaliano, Peter Meikle, John J. Hopwood, Kunio Nagashima, Kanneboyina Nagaraju, Paul H. Plotz
Journal: Molecular Therapy (2004)

Pompe disease (type II glycogen storage disease) is an autosomal recessive disorder caused by a deficiency of lysosomal acid α-glucosidase (GAA) leading to the accumulation of glycogen in the lysosomes primarily in cardiac and skeletal muscle. The recombinant human GAA (rhGAA) is currently in clinical trials for enzyme replacement therapy of Pompe disease. Both clinical data and the results of preclinical studies in our knockout model of this disease show that rhGAA is much more effective in resolving the cardiomyopathy than the skeletal muscle myopathy. By contrast, another form of human GAA—transgenic enzyme constitutively produced in liver and secreted into the bloodstream of knockout mice (Gaa−/−)—completely prevented both cardiac and skeletal muscle glycogen accumulation. In the experiments reported here, the transgenic enzyme was much less efficient when delivered to skeletal muscle after significant amounts of glycogen had already accumulated. Furthermore, the transgenic enzyme and the rhGAA have similar therapeutic effects, and both efficiently clear glycogen from cardiac muscle and type I muscle fibers, but not type II fibers. Low abundance of proteins involved in endocytosis and trafficking of lysosomal enzymes combined with increased autophagy in type II fibers may explain the resistance to therapy.
Less restricted mating, low contact with kin, and the role of culture
Authors: Lesley Newson, Tom Postmes
Journal: Behavioral and Brain Sciences (2005)

On the basis of a reinterpretation of the International Sexuality Description Project (ISDP) data, we suggest that findings are consistent with the view that human reproductive behaviour is largely under social control. Behaviours associated with a high Sociosexual Orientation Index (SOI) may be part of a progressive change in reproductive behaviour initiated by the dispersal of kin that occurs as societies modernize.
Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex I insults
Authors: Daniel Alvarez-Fischer, Julia Fuchs, François Castagner, Olivier Stettler, Olivia Massiani-Beaudoin, Kenneth L Moya, Colette Bouillot, Wolfgang H Oertel, Anne Lombès, Wolfgang Faigle, Rajiv L Joshi, Andreas Hartmann, Alain Prochiantz
Journal: Nature Neuroscience (2011)
Official resigns amid prostate screening controversy
Authors: J. Lenzer
Journal: BMJ (2010)

A medical officer with a federal US health agency is resigning his position amid a controversy about who should be screened for prostate cancer.

Kenny Lin, a family physician and medical officer with the Agency for Healthcare Research and Quality, which provides scientific support to the independent US Preventive Services Task Force, wrote in his blog that “politics trumped science” after a two day meeting that was due to begin on 1 November was abruptly cancelled (http://commonsensemd.blogspot.com/2010/11/meeting-that-wasnt-and-surprise.html).

The task force was about to vote on recommendations about prostate cancer screening and was likely to have come down against its routine use on men of all ages. If it had done so it …
Horner's syndrome and headache due to carotid artery disease.
Authors: T E West, R J Davies, R E Kelly
Journal: BMJ (1976)

Horner9s syndrome was accompanied by ipsilateral pain in the head, face, or neck in eight patients. In all cases angiography showed narrowing of the internal carotid artery in a pattern compatible with dissection within the arterial wall. In one patient in whom this diagnosis was substantiated by surgical exploration biopsy of the arterial wall showed changes typical of cystic medial necrosis. It is suggested that this clinical presentation constitutes a distinct syndrome.
p53 Plays an Important Role in Cell Fate Determination after Exposure to Microcystin-LR
Authors: Shota Takumi, Masaharu Komatsu, Tatsuhiko Furukawa, Ryuji Ikeda, Tomoyuki Sumizawa, Hitomi Akenaga, Yuta Maeda, Kohji Aoyama, Koji Arizono, Seiichi Ando, Toru Takeuchi
Journal: Environmental Health Perspectives (2010)

BackgroundMicrocystin-LR, a cyclic heptapeptide, possesses the ability to inhibit the serine/threonine protein phosphatases PP1 and PP2A and, consequently, exhibits acute hepatocytotoxicity. Moreover, microcystin-LR induces cellular proliferation, resulting in tumor-promoting activity in hepatocytes. However, mechanisms that regulate the balance between cell death and proliferation after microcystin-LR treatment remain unclear.ObjectiveWe examined the contribution of the transcription factor p53, as well as that of the hepatic uptake transporter for microcystin-LR, organic anion transporting polypeptide 1B3 (OATP1B3), to the cellular response to microcystin-LR exposure.MethodsWe analyzed intracellular signaling responses to microcystin-LR by immunoblotting and real-time reverse-transcriptase polymerase chain reaction techniques using HEK293 human embryonic kidney cells stably transfected with SLCO1B3 (HEK293-OATP1B3). In addition, we analyzed the effect of attenuation of p53 function, via the p53 inhibitor pifithrin-α, and knockdown of p53 mRNA on the cytotoxicity of microcystin-LR using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.ResultsMicrocystin-LR induced the phosphorylation and accumulation of p53 in HEK293-OATP1B3 cells, which resulted in up-regulation of the expression of p53 transcript targets, including p21 and seven in absentia homolog 1 (siah-1). In addition, microcystin-LR activated Akt signaling through the phosphorylation of Akt and glycogen synthase kinase 3β. Although Akt signaling was activated, the accumulation of p53 led cells to apoptosis after treatment with 50 nM microcystin-LR for 24 hr. Both pharmacological inhibition of transcription factor activity of p53 by pifithrin-α and knockdown of p53 with small hairpin RNA attenuated the susceptibility of HEK293-OATP1B3 cells to microcystin-LR.ConclusionsThis study demonstrates the importance of p53 in the regulation of cell fate after exposure to microcystin-LR. Our results suggest that, under conditions of p53 inactivation (including p53 mutation), chronic exposure to low doses of microcystin-LR may lead to cell proliferation through activation of Akt signaling. Results of this study may contribute to the development of chemoprevention and chemotherapeutic approaches to microcystin-LR poisoning.
Obstruction of Left Ventricular Outlet in Association with Ventricular Septal Defect
Authors: RONALD M. LAUER, JAMES W. DUSHANE, JESSE E. EDWARDS
Journal: Circulation (1960)

In a pathologic collection of 722 congenital heart lesions we have observed 10 cases in which a ventricular septal defect was associated with obstruction to normal left ventricular outflow. These cases are presented in the framework of a classification relating hemodynamics to the position of the obstructing lesion and the size of the ventricular septal defect. One additional case observed clinically and at operation is also reported to make more nearly complete the classification of the anatomic arrangements in which the common denominators are ventricular septal defect and obstruction to normal ventricular outflow.
Warfarin Dose Assessment Every 4 Weeks Versus Every 12 Weeks in Patients With Stable International Normalized Ratios
Authors: Sam Schulman, Sameer Parpia, Clare Stewart, Lisa Rudd-Scott, Jim A. Julian, Mark Levine
Journal: Annals of Internal Medicine (2011)

Guidelines recommend that patients receiving warfarin undergo international normalized ratio (INR) monitoring every 4 weeks.To investigate whether assessment of warfarin dosing every 12 weeks is as safe as assessment every 4 weeks.Noninferiority randomized trial. The randomization schedule (in a 1:1 ratio) was computer-generated, and allocation was concealed until the database was locked by using a centralized schedule. Patients, study and clinical personnel, adjudicators of clinical events, and the study statistician were blinded to treatment assignment. (ClinicalTrials.gov registration number: NCT00356759) SETTING: Single center in Hamilton, Ontario, Canada.250 patients receiving long-term warfarin therapy, whose dose was unchanged for at least 6 months; 226 completed the study.Dosing assessment every 12 weeks (n = 124) compared with every 4 weeks (n = 126) for 12 months. Patients in the 12-week group were tested every 4 weeks; sham INRs within the target range were reported for two of the three 4-week periods.Percentage of time in the therapeutic range (primary outcome) and number of extreme INRs, changes in maintenance dose, major bleeding events, objectively verified thromboembolism, and death (secondary outcomes).The percentage of time in the therapeutic range was 74.1% (SD, 18.8%) in the 4-week group compared with 71.6% (SD, 20.0%) in the 12-week group (absolute difference, 2.5 percentage points [1-sided 97.5% upper confidence bound, 7.3 percentage points]; noninferiority P = 0.020 for a 7.5-percentage point margin). Fewer patients in the 12-week group than in the 4-week group had any dose changes (37.1% vs. 55.6%; absolute difference, 18.5 percentage points [95% CI, 6.1 to 30.0 percentage points]; P = 0.004). Secondary outcomes did not differ between groups.Patients in the 12-week group had testing and contact with clinic staff every 4 weeks. The study was conducted at a single center and used surrogate outcomes.Assessment of warfarin dosing every 12 weeks seems to be safe and noninferior to assessment every 4 weeks. A comparison of INR testing, patient contact, and warfarin dose assessment every 12 weeks versus every 4 weeks is necessary before INR testing every 12 weeks can be routinely recommended for practice.Physicians' Services Incorporated Foundation.
Coronary-Artery Spasm and Myocardial Infarction
Authors: C. Richard Conti
Journal: New England Journal of Medicine (1983)

IN this issue, Vincent et al. report a tantalizing and well-documented account of a young woman who had a myocardial infarction despite angiographically normal coronary arteries.1 The sequence of events suggests that coronary spasm was the initiating factor. However, it is still possible that an embolus from the catheter could have initiated spasm, which resulted in further stasis and further clot formation. As shown in Figure 4 in their paper, the clot was seen almost immediately after the development of a transient decrease in the size of the coronary-artery lumen. This seems rather rapid for thrombus formation in a patient . . .
Peroral endoscopic myotomy (POEM) in a 3-year-old girl with severe growth retardation, achalasia, and Down syndrome
Authors: R. Maselli, H. Inoue, M. Misawa, H. Ikeda, T. Hosoya, M. Onimaru, A. Yoshida, N. Eleftheriadis, K. Suzuki, S. Kudo
Journal: Endoscopy (2012)

Achalasia is a primary motility disorder with an annual incidence of 0.11 cases/100 000 children [1]. In the field of natural orifice transluminal endoscopic surgery (NOTES), the peroral endoscopic myotomy (POEM) [2] [3] is the only treatment to be performed routinely in humans. We report the case of a 3-year old female patient with Down syndrome who presented with severe growth retardation and weight at less than the 3 rd percentile curve. Achalasia was suspected because of vomiting, recurrent cough, aspiration pneumonia, and growth retardation; it was confirmed by barium esophagogram, endoscopy, and esophageal manometry.
Long-standing remission of recalcitrant juvenile pemphigus vulgaris after adjuvant therapy with rituximab
Authors: E. Schmidt, S. Herzog, E-B. Brocker, D. Zillikens, M. Goebeler
Journal: British Journal of Dermatology (2005)

Journal Article Long‐standing remission of recalcitrant juvenile pemphigus vulgaris after adjuvant therapy with rituximab Get access E. Schmidt, E. Schmidt Department of Dermatology, University of Würzburg, 97080 Würzburg, Germany Search for other works by this author on: Oxford Academic Google Scholar S. Herzog, S. Herzog Department of Dermatology, University of Würzburg, 97080 Würzburg, Germany Search for other works by this author on: Oxford Academic Google Scholar E‐B. Bröcker, E‐B. Bröcker Department of Dermatology, University of Würzburg, 97080 Würzburg, Germany Search for other works by this author on: Oxford Academic Google Scholar D. Zillikens, D. Zillikens Department of Dermatology, University Hospital of Schleswig‐Holstein, Campus Lübeck, 23538 Lübeck, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Goebeler M. Goebeler Department of Dermatology, University of Würzburg, 97080 Würzburg, GermanyDepartment of Dermatology, University Medical Center Mannheim, University of Heidelberg, Theodor‐Kutzer‐Ufer, 68135 Mannheim, Germany Matthias Goebeler E‐mail: matthias.goebeler@haut.ma.uni‐heidelberg.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 2, 1 August 2005, Pages 449–451, https://doi.org/10.1111/j.1365-2133.2005.06740.x Published: 01 August 2005
Abstract 586: Withaferin-A inhibits prostate tumor growth by enhancing anti-tumor immune response
Authors: Rajesh Singh, William E. Grizzle, James W. Lillard, Shailesh Singh
Journal: Cancer Research (2012)

Abstract Indolent nature of prostate cancer provides a ‘large window’ of opportunity for chemopreventive strategies. Most chemopreventive strategies are primarily focused on controlling and/or reversing the mechanisms involved in neoplastic transformation and cancer progression. It is now well accepted that tumors evade the patient's defense system during progression and growth at distant sites. Mounting evidences suggest immunological defects in prostate cancer patients with higher numbers of functionally suppressive CD4+CD25+FOXP3+ T cells (Treg) and lower number of effectors T cells. Furthermore, tumor microenvironment exerts a profound immunosuppressive effect on effectors T cells by secreting TGF-β and IL-10. Therefore, modulating TGF-β and IL-10 using natural and dietary components constitutes an innovative approach for prostate cancer prevention and treatment. In this study, we have shown that Withaferin-A (WA), a bioactive compound isolated from Withania Somnifera also called “Ashwagandha” has the ability to modulate immunosuppressive cytokines (IL-10 and TGF-β) produced by the prostate cancer cells. Additionally, we show selective inhibition of Treg proliferation and induction of apoptosis in Tregs cells in immune competent prostate cancer mouse model treated with WA compared to controls. Our results suggest that WA have potential to fine-tune immunosuppressive phenotype of tumor-associated lymphocytes by modulating immuno-suppressive cytokines. Significant inhibition of tumor growth in immune competent prostate cancer mouse model as compared to immune deficient xenograft suggest potential role of WA on reversal of anti-tumor immune response from immune suppression to immune competence, which is required to fight against prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 586. doi:1538-7445.AM2012-586
PATENT FORAMEN OVALE CLOSURE WITH A CONVENTIONAL RADIOFREQUENCY ABLATION CATHETER: EARLY FEASIBILITY
Authors: Luigi Di Biase, J. David Burkhardt, Rodney Horton, Javier Sanchez, Prasant Mohanty, Mitra Mohanty, Dimpi Patel, Shane Bailey, G. Joseph Gallinghouse, Andrea Natale
Journal: Journal of the American College of Cardiology (2010)