tbuckley/cabot-search huggingface dataset:
Confocal Microscopic Analysis of the Interaction between Cisplatin and the Copper Transporter ATP7B in Human Ovarian Carcinoma Cells
Authors: Kuniyuki Katano, Roohangiz Safaei, Goli Samimi, Alison Holzer, Mika Tomioka, Murray Goodman, Stephen B. Howell
Journal: Clinical Cancer Research (2004)

Some cisplatin (DDP)-resistant cells overexpress the copper export transporter ATP7B, and cells molecularly engineered to overexpress ATP7B are resistant to DDP. The interaction of Cu with ATP7B normally triggers its relocalization from the perinuclear region to more peripheral vesicles. To investigate the interaction of DDP with ATP7B, we examined the effect of DDP on the subcellular localization of ATP7B using human ovarian carcinoma cells expressing a cyan fluorescent protein (ECFP)-tagged ATP7B (2008/ECFP-ATP7B). ATP7B expression was confirmed in 2008/ECFP-ATP7B cells by Western blotting, and its functionality was documented by showing that it rendered the cells 1.9-fold resistant to CuSO(4) and 4.1-fold resistant to DDP and also reduced the accumulation of both drugs. There was greater sequestration of Pt into intracellular vesicles in the 2008/ECFP-ATP7B cells than in the 2008/ECFP cells. Confocal digital microscopy revealed that ECFP-ATP7B localized in the perinuclear region in absence of drug exposure and that both Cu and DDP triggered relocalization to more peripheral vesicular structures. A fluorescein-labeled form of DDP that retained cytotoxicity and was subject to the same mechanisms of resistance as DDP colocalized with ECFP-ATP7B in the 2008/ECFP-ATP7B cells, whereas the same fluorochrome lacking the DDP moiety did not. These results provide evidence that DDP directly interacts with ATP7B to trigger its relocalization and that ATP7B mediates resistance to DDP by sequestering it into vesicles of the secretory pathway for export from the cell.
Cow's milk provocation induces an immune response to unrelated dietary antigens.
Authors: H Suomalainen, E Isolauri, M Kaila, E Virtanen, H Arvilommi
Journal: Gut (1992)

The activation of immune mechanisms was evaluated by the solid phase enzyme linked immunoassay of immunoglobulin and specific antibody secreting cells in 27 patients (aged from nine to 69 months), subjected to a diagnostic cow9s milk challenge or a rechallenge. A significant rise in the total number of immunoglobulin secreting cells was associated with clinically positive (n = 17), but not a negative (n = 10) cow9s milk challenge in all immunoglobulin isotypes. The number of specific antibody secreting cells against beta lactoglobulin, mean (95% confidence interval), increased from 4.8 (1.4, 15.8) to 16.9 (5.5, 52.7) specific antibody secreting cells/10(6) cells, p = 0.02, and against casein from 2.2 (0.8, 6.1) to 7.5 (2.5, 22.5) specific antibody secreting cells/10(6) cells, p = 0.01, in patients positive to challenge in the IgM class only, indicating defective immune elimination of milk antigens. In addition to the specific immune response to cow9s milk antigens, an increase in IgM specific antibody secreting cells against an unrelated dietary antigen, gliadin, from 8.2 (2.1, 31.1) to 31.0 (14.2, 67.6) specific antibody secreting cells/10(6) cells, p = 0.01, was observed. These results indicate that cow9s milk challenge, in patients who have cow9s milk allergy, induces a strong non-antigen specific immune response that includes a response against unrelated antigens concomitantly present in the intestinal lumen. Activation of such immune mechanisms may hence reflect increased antigenic load caused by the immune mediated lesion in the gut mucosa.
Book Review Atherothrombosis and Coronary Artery Disease Second edition. Edited by Valentin Fuster, Eric J. Topol, and Elizabeth G. Nabel. 1636 pp., illustrated. Philadelphia, Lippincott Williams &amp; Wilkins, 2005. $149. 0-7817-3583-1
Authors: Patrick Vallance
Journal: New England Journal of Medicine (2005)
Embolectomy from Arteries of the Lower Limbs
Authors: Field C. Leonard
Journal: New England Journal of Medicine (1954)

EMBOLISM to an arterial bifurcation is at best a clinical impression. Positive diagnosis depends on removal of the embolus. For this reason most papers on the subject have been limited to surgical cases. During the four-year period 1950–1953 I saw and treated conservatively a number of probable brachial and popliteal or tibial emboli without loss of life or limb. In the same period 15 embolectomies among 13 subjects were performed at the aortic, iliac and femoral bifurcations.Except for collective reviews individual series have been small. Warren and Linton,1 in 1948, reported 18 aortic, iliac and femoral embolectomies by several . . .
Targeting Notch Signaling with a Notch2/Notch3 Antagonist (Tarextumab) Inhibits Tumor Growth and Decreases Tumor-Initiating Cell Frequency
Authors: Wan-Ching Yen, Marcus M. Fischer, Fumiko Axelrod, Christopher Bond, Jennifer Cain, Belinda Cancilla, William R. Henner, Rene Meisner, Aaron Sato, Jalpa Shah, Tracy Tang, Breanna Wallace, Min Wang, Chun Zhang, Ann M. Kapoun, John Lewicki, Austin Gurney, Timothy Hoey
Journal: Clinical Cancer Research (2015)

The Notch pathway plays an important role in both stem cell biology and cancer. Dysregulation of Notch signaling has been reported in several human tumor types. In this report, we describe the development of an antibody, OMP-59R5 (tarextumab), which blocks both Notch2 and Notch3 signaling.We utilized patient-derived xenograft tumors to evaluate antitumor effect of OMP-59R5. Immunohistochemistry, RNA microarray, real-time PCR, and in vivo serial transplantation assays were employed to investigate the mechanisms of action and pharmacodynamic readouts.We found that anti-Notch2/3, either as a single agent or in combination with chemotherapeutic agents was efficacious in a broad spectrum of epithelial tumors, including breast, lung, ovarian, and pancreatic cancers. Notably, the sensitivity of anti-Notch2/3 in combination with gemcitabine in pancreatic tumors was associated with higher levels of Notch3 gene expression. The antitumor effect of anti-Notch2/3 in combination with gemcitabine plus nab-paclitaxel was greater than the combination effect with gemcitabine alone. OMP-59R5 inhibits both human and mouse Notch2 and Notch3 function and its antitumor activity was characterized by a dual mechanism of action in both tumor and stromal/vascular cells in xenograft experiments. In tumor cells, anti-Notch2/3 inhibited expression of Notch target genes and reduced tumor-initiating cell frequency. In the tumor stroma, OMP-59R5 consistently inhibited the expression of Notch3, HeyL, and Rgs5, characteristic of affecting pericyte function in tumor vasculature.These findings indicate that blockade of Notch2/3 signaling with this cross-reactive antagonist antibody may be an effective strategy for treatment of a variety of tumor types.
Molecular Properties of Corticosteroid Binding Globulin and the Sex-Steroid Binding Proteins*
Authors: GEOFFREY L. HAMMOND
Journal: Endocrine Reviews (1990)

AVARIETY of extracellular binding proteins enhance the solubility of steroid hormones in biological fluids and facilitate their transport from steroidogenic tissues to target cells (1). In mammals, albumin is quantitatively the most important of these proteins and provides a large reservoir of loosely bound hormone that may be released within some target tissues (2). Two albumin-related proteins, vitamin D binding protein and α-fetoprotein, also appear to have arisen by duplication of a common ancestral gene (3) and are characterized by higher affinities and specificities for steroid ligands. The molecular composition and structure of the vitamin D binding protein have already been described in detail (4), and this review will concentrate on the molecular properties of two other biologically important classes of extracellular steroid binding proteins: corticosteroid binding globulin (CBG) and the sex-steroid binding proteins; sex hormone binding globulin (SHBG) and androgen binding protein (ABP). These proteins are far less abundant than those of the albumin superfamily, but they bind biologically active steroid hormones with remarkably high affinity and specificity. As a result, they not only transport steroid hormones but also modulate steroid bioavailability (5), and may participate directly in the delivery of steroids to certain cells by interaction with plasma membrane receptors (6). Indeed, it is becoming increasingly obvious that their activities may be attributed to unique structural properties; a greater understanding of which may help define their physiological importance.
What Matters Magnesium?
Authors: Nasser M. Gayed
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Whang and Ryder<sup>1</sup>show that 53% of their serum samples had an abnormal magnesium level, most of them unsuspected clinically. However, they do not present sufficient evidence to justify their recommendation that "serum magnesium be included routinely when serum electrolyte measurements are required in the care of patients." To recommend that any such case finding or screening protocol be instituted (irrespective of the patient's symptoms), it is not sufficient merely to show that the condition in question is common. The authors have to show also that the condition is serious and treatable, and has an asymptomatic stage; furthermore, treatment in the asymptomatic phase must result in a therapeutic outcome superior to that obtained by delaying treatment until symptoms appear.<sup>2</sup>The authors give no information on the clinical condition of the patients or their outcome. The study does not include any information regarding treatment of the
The Jumping Frenchmen Of Maine
Authors: Eric R. Sanderson
Journal: JAMA (1967)

<h3>To the Editor:—</h3> I want to thank you and Dr. Charles Kunkle for again calling attention to the Jumping Frenchmen of Maine (<b>200</b>: 406, 1967). I was the local authority on jumping of all sorts, as far back as 1962, and submit an item from the<i>King County Medical Society Bulletin</i>(March 1962) in evidence. I know now how the man who invented Six-Up feels, when he thinks how close he came to fame. <i>To insure Dr. Sanderson's niche in history, his contribution is reprinted here</i>.—Ed. There is this controversy going on right now about jumping. Some fellow took a pole and vaulted over a bar sixteen feet high and that is a record. The other fellows who haven't been able to make it that high are crying foul. They are saying the new fiber glass pole is so constructed that it will throw you higher than that
Quality improvement scheme hopes to save authority 17m in first year
Authors: Z. Kmietowicz
Journal: BMJ (2008)

A pioneering scheme that pays hospitals a bonus for delivering the best quality care is being rolled out across the NHS North West region of England after a trial showed it gave incentives to clinicians in a way that government reforms have failed to do.

The scheme, entitled Advancing Quality, has been developed by the strategic health authority NHS North West to improve the region’s poor health and to improve patients’ hospital experience. It pays the best performing hospitals a bonus on top of what they receive through Payment by Results, the national system by which hospitals are paid for the procedures they carry out. …
Anticardiolipin Antibody Quantitation
Authors: CHENG HWEE MING
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 December 1987Anticardiolipin Antibody QuantitationCHENG HWEE MING, PH.D.CHENG HWEE MING, PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-6-941_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Petri and associates (1) reported a sensitive enzyme-linked immunosorbent assay (ELISA) for anticardiolipin antibody that detected reactive plasma samples, defined as having greater than 42.3 ng of bound immunoglobulin per milliliter.In a recent international workshop on anticardiolipin antibody assay, Harris and coworkers (2) proposed the adoption of a GPL unit, the unit of activity of a standardized affinity-purified serum from a patient with a high IgG anticardiolipin antibody. Their established lower limit of sensitivity was 5 GPL units, equivalent to the binding activity of 5 µg/mL of IgG anticardiolipin antibody. By comparison, the method of Petri...References1. PETRIRHEINSCHMIDTWHITING-O'KEEFEHELLMANCORASH MMQDL. The frequency of lupus anticoagulant in systemic lupus erythematosus: a study of sixty consecutive patients by activated partial thromboplastin time, Russell viper venom time, and anticardiolipin antibody level. Ann Intern Med. 1987;106:524-31. LinkGoogle Scholar2. HARRISGHARAVIPATELHUGHES EASG. Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986. Clin Exp Immunol. 1987;68:215-22. MedlineGoogle Scholar3. HARRISGHARAVITINCANI EAA. Affinity purified anti-cardiolipin and anti-DNA antibodies. J Clin Lab Immunol. 1985;17:155-62. MedlineGoogle Scholar4. EILAT D. Anti-DNA antibodies: problems in their study and interpretation. Clin Exp Immunol. 1986;65:215-22. MedlineGoogle Scholar5. ENGVALLPERLMANN EP. Enzyme-linked immunosorbent assay, ELISA: quantitation of specific antibodies by enzyme-labelled anti-immunoglobulin in antigen-coated tubes. J Immunol. 1972;109:129-35. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Physiology Faculty of Medicine University of Malaya 59100 Kuala Lumpur Malaysia. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByClinical significance of a single test for anti-cardiolipin antibodies in patients with systemic lupus erythematosus 1 December 1987Volume 107, Issue 6Page: 941-942KeywordsBlood plasmaEnzyme linked immunosorbent assay Issue Published: 1 December 1987 PDF DownloadLoading ...
An Informal Appraisal of the Current Status of 'Medical Sociology'
Authors: Robert G. Petersdorf
Journal: JAMA (1981)

Chairpersons of departments of medicine, pediatrics, and family medicine were sent a questionnaire to determine their experience with, and attitude toward, medical sociology. The results showed that between 40% and 50% of medical students are taught medical sociology during their preclinical years, usually by several departments. Formal instruction was far less common during clinical clerkships and house staff training, although topics dealing with medical sociology were occasionally the subject of grand rounds. The commitment to teaching medical sociology was greatest in departments of family medicine, and least in departments of medicine, with departments of pediatrics occupying an intermediate position. A similar gradient was evident in commitment of departmental resources and enthusiasm for the subject. In general, departments of medicine held a negative attitude toward medical sociology, while departments of family medicine thought the subject was important and worthwhile.
Doctors should consult patients before imposing non-resuscitation notices unless it would cause harm, Court of Appeal rules
Authors: C. Dyer
Journal: BMJ (2014)

An NHS trust breached a patient’s human rights when doctors placed a “do not attempt cardiopulmonary resuscitation” (DNACPR) notice on her records without her knowledge, the Court of Appeal has ruled.

Cambridge University Hospitals NHS Foundation Trust violated Janet Tracey’s right to respect for her private life in not discussing the decision with her, declared three senior judges headed by the Master of the Rolls, Lord Dyson.

“A DNACPR decision is one which will potentially deprive the patient of lifesaving treatment,” said Dyson. “There need to be convincing reasons not to involve the patient.”

Tracey had had terminal lung cancer diagnosed two weeks before she …
Reduced Left Ventricular Ejection Fraction is Associated with Mismatch on Combined 201TI/123I Meta-iodobenzylguanidine Scan and Predicts Inducibllity of Ventricular Arrhythmia Following Anterior Myocardial Infarction
Authors: A P Ignaszcwski, L X McCormick, B I Jugdutt, S S Gulamhussein, D P Humen
Journal: Clinical Nuclear Medicine (1994)

Ignaszcwski, A P; McCormick, L X; Jugdutt, B I; Gulamhussein, S S; Humen, D P Author Information
Dermatology training in the U.K.: does it reflect the changing demographics of our population?
Authors: A. Salam, O.E. Dadzie
Journal: British Journal of Dermatology (2013)

Funding sources: Funding for this study was provided by London Ethnic Skin Limited. Dear Editor, The U.K. has seen an increase in the proportion of the 'nonwhite' population by 61% between 2001 (8·7%) and 2011 (14%), with the proportion of black Africans doubling over this period.1 Studies have shown that among different ethnic and racial groups, cutaneous disorders may vary in both prevalence and clinical manifestation.2 In light of this, as well as the observed changes in the U.K. demographics, it is important that dermatologists are adequately trained to diagnose and manage dermatoses pertinent to our ethnic population. For this reason, we conducted a questionnaire‐based study to ascertain whether the current U.K. dermatology training programme for specialist registrars provides adequate training in the diagnosis and management of diseases pertinent to the ethnic population. We identified 217 dermatology trainees (specialty training level ST3–ST6, including those out of programme) and 77 junior consultants (within 2 years of receiving their Certificate of Completion of Specialist Training) from the database of the U.K. Joint Royal Colleges of Physicians Training Board (JRCPTB) as being eligible for inclusion into the study. A web link to our online questionnaire was sent to this target group via: (i) the monthly e‐mail bulletin of the British Association of Dermatologists (BAD); (ii) letters posted to all National Health Service hospitals with a dermatology department in the U.K.; and (iii) an e‐mail bulletin distributed twice to dermatology trainees via regional trainee representatives.
Prevention of Coronary Heart Disease in Practice-Reply
Authors: Nemat O. Borhani
Journal: JAMA (1986)

<h3>In Reply.—</h3> Dr Wynder's complimentary words about my article are gratifying. For those of us who, like Dr Wynder, have devoted our entire career to preventive medicine, the downward secular trend in coronary heart disease mortality is encouraging. In general, I agree with Dr Wynder's reference to Virchow's observation on "crowd diseases." Although I concur with his analogy for primary prevention of coronary heart disease, I would change the words "a common factor" to "a combination of<i>multiple</i>factors," affecting a sizable proportion of a population. Perhaps Dr Wynder has misunderstood the position that was put forth in my article.<sup>1</sup>I did not advocate that we should "ignore the large population of Americans destined to develop coronary heart disease," as Dr Wynder says. This statement is unfortunate; it neither represents my position nor accurately reflects the points made in the article. I, also, believe that every child and adult
Abstract 5497: Targeting glioblastoma stem cells with withaferin A
Authors: Baoyu Zhang, Branko Cuglievan, Nadia G. Myrthil, Steven Vanni, Ricardo J. Komotar, Regina M. Graham
Journal: Cancer Research (2014)

Abstract Introduction. Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer affecting 3 to 4 per 100,000 people annually in the United States. Despite aggressive therapy including surgical resection followed by both radiation and chemotherapy, overall survival remains dismal at approximately 14 months. Recent studies have determined that GBM's contain a small population of stem cells (GSCs), which promote tumor growth through unlimited self-renewal. Since GSCs are chemo- and radio-resistant and drive tumor regrowth following therapy, successful treatment depends on the elimination of these cells. Withaferin A (WA) is a bioactive compound derived from the plant Withonia somnifera which possesses anti-inflammatory and anti-cancer properties. Here we evaluated the effects of WA on patient derived GSCs. Methods. With IRB approval, GSC lines were generated. GSCs were propagated in neurosphere media and examined for the stem cell markers CD133, nestin, musashi and BMi1 by immunocytochemistry and western blot analysis. Effect of WA on cell viability was determined using MTS assay. The effect of WA on cell survival and stress pathways was evaluated by western blot analysis. Results. WA induced a significant decrease in cell viability at low micromolar concentrations. The IC50 for 3 patient derived GSC lines ranged between 0.96-1.78μM. WA induced ER stress and apoptosis in the GSCs as indicated by increased expression of ER stress markers grp78 and CHOP and increased levels of cleaved PARP. Furthermore, WA decreased survivin but increased phospho-ERK levels. However, inhibition of ERK activity with U0126 did not potentiate the effect of WA on cell death. Conclusion. Ashwagandha has been used safely for medicinal purposes for centuries and pharmacokinetic studies in mice indicate that micromolar plasma concentrations of WA are obtainable. Our studies indicate that very low concentrations of WA induce ER stress and cell death in GSC lines. Targeting GSC with WA may increase patient survival by hindering GSC mediated tumor regrowth following surgery. Our data demonstrates the efficacy of WA and supports additional studies toward the use of WA as an adjuvant GBM therapy. Citation Format: Baoyu Zhang, Branko Cuglievan, Nadia G. Myrthil, Steven Vanni, Ricardo J. Komotar, Regina M. Graham. Targeting glioblastoma stem cells with withaferin A. [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 5497. doi:10.1158/1538-7445.AM2014-5497
The clinical significance of exercise-induced ST-segment elevation.
Authors: R A Chahine, A E Raizner, T Ishimori
Journal: Circulation (1976)

The significance of exercise-induced ST-segment elevation remains unsettled. We reviewed the treadmill tests of 840 consecutive patients and exercise-induced ST-segment elevation was noted in 29 (3.5%). Only eight of these (28%) stopped because of angina. Anterior myocardial infarction (AMI) was found on the resting electrocardiogram in 25 (85%). Angiographic studies performed on 21 showed critical lesions of the left anterior descending (LAD) in 19 (90%) and left ventricular aneurysm in 18 (86%). When all the patiens who had AMI or critical LAD obstruction during the study period were reviewed, only 22% and 18% respectively showed exercise-induced ST-segment elevation, while 64% of the cases with left ventricular aneurysm displayed this phenomenon. Thus, exercise-induced ST elevation seems to reflect the presence of severe coronary artery disease most commonly with an associated left ventricular aneurysm and may relate more to the abnormal wall motion than to the myocardial ischemia per se.
EFFECTS OF INTRATRACHEAL MEDICATION ON GAS BURNS OF THE RESPIRATORY TRACT
Authors: LAFAYETTE PAGE
Journal: JAMA (1922)

When we entered the war, the enemy was using mixed gases, thrown over with shells from trench mortars and by heavy artillery. The attacks usually began with gases which produced excessive sneezing and lacrimation; this being followed by the more poisonous gases, mustard and phosgen. Mustard gas, so called because its odor resembles that of mustard oil, classified as a vesicant, causes inflammation, blistering, discoloration of skin, acute conjunctivitis and intense inflammation of the respiratory passages. Its action is caustic, the extent of damage or destruction of tissue depending on the degree of concentration and the time of exposure. Its action may be delayed over a few hours to two or three days. Phosgen is classified as a lung irritant of suffocant type, which, in the alveoli and lung tissues, causes exudation of large quantities of frothy mucus; acute pulmonary edema, and death, by flooding the air spaces. One of