tbuckley/cabot-search huggingface dataset:
Abstract P2-06-19: Transferrin Receptor (CD71) Identifies Poor Response to Tamoxifen in Oestrogen Receptor Positive Breast Cancer Patients
Authors: RI Nicholson, HO Habashy, JM Gee, P Finlay, L Farrow, B Jasani, P Barrett-Lee, JF Robertson, IO. Ellis
Journal: Cancer Research (2010)

Abstract Background: CD71 is involved in the cellular uptake of iron and is expressed on cells with high proliferation. Interestingly, we have Interestingly, we shown that its expression is associated with elevated tumour proliferation, shortened breast cancer specific survival and worsened outlook in ER+ adjuvant tamoxifen treated early breast cancer patients (Habashy et al, 2010). Here we extend our studies of the relationship between CD71 and tamoxifen outcome by study of an exploratory series of patients where endocrine response was directly assessable. Material and Methods: CD71 (clone 10F11 antibody; Abcam, Cambridge, UK) and proliferation (MIB1) immunohistochemistry were performed as described in Habashy et al (2010) on 87 formalin fixed paraffin-embedded breast cancers. These were obtained from patients within the Nottingham Tenovus Multiple Antibody Study who had received systemic tamoxifen therapy for locally advanced primary carcinoma or metastatic disease or for recurrence after surgery alone. All had lesions assessable for response quality at 6 months, with survival and duration of antihormone response measured from initiation of antihormone to death or progression on therapy respectively. 48 tumours were classified as ER+ and 39 ER-. Results: Within this tamoxifen treated series, 68/87 patients were deemed positive for CD71 (plasma membrane and cytoplasmic), showing HScore values &amp;gt;=5. In the ER+ subgroup, a greater clinical response rate to tamoxifen was seen in CD71 — tumours (10 CR/PR, 3 S and 2 P) versus their CD71+ counterparts (CR/PR, 11 S and 16 P, p=0.015). CD71 positivity was associated with a significantly shortened time to progression and death (Kaplan Meier Test, p=0.026 and p=0.005 respectively). Examination of the proliferation marker MIB1 in ER+ tumours revealed a positive association with CD71 expression (Spearman's Test, p=0.01). In ER-patients, comprising predominantly progressive disease on tamoxifen therapy, CD71 status showed no impact on either time to progression of the disease or death. Discussion: The present study extends our novel findings relating CD71 expression to loss of response to tamoxifen in ER+ breast cancer and reveals CD71 associates with increased tumour cell proliferation in clinical disease. Whether CD71 plays a causative role in the direction of these events and can be targeted to improve endocrine response requires to be ascertained. Habashy HO et al, 2010, Breast Cancer Research and Treatment 119:283-293 Abd El-Rehim DM et al, 2005, Int J Cancer 116: 340-350 Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-19.
Abstract 2225: The molecular architecture of p85α as determined by SAXS and chemical cross-linking.
Authors: Evan T. Brower, Sandra B. Gabelli, Qing Wang, Raghothama Chaerkady, Christopher E. Berndsen, Robert N. Cole, Jonathan M. Backer, Mathias Schäfer, Andrea Sinz, Kenneth W. Kinzler, Bert Vogelstein, L. Mario Amzel
Journal: Cancer Research (2013)

Abstract The p85α protein, encoded by PIK3R1, is the regulatory subunit of phosphatidylinositol 3-kinase alpha (PI3Kα). The role of p85α extends to regulation of PTEN-phosphatase activity, the unfolded protein response, and additional cellular pathways. PIK3R1 was recently identified as frequently mutated in glioblastomas and endometrial cancers. Small-angle X-ray scattering (SAXS) and chemical cross-linking were used to complete the first investigation of the shape and molecular organization of full length p85α. p85α is elongated in shape and exists in a conformation conducive to p110α binding. The p85α structural data was utilized to generate the first model of the full length PI3K complex. Cancer associated PIK3R1 mutations are localized to interfaces between p85α domains, and in the context of the PI3K complex, are clustered at regions comprising the interface of the catalytic and regulatory subunits. A potential interface was discovered between the RhoGAP domain of p85α and the p110α kinase domain. GTPases may enhance PI3K activity by binding to the RhoGAP domain, thereby attenuating the interaction between the RhoGAP and the kinase domain. These data provide the structural groundwork required for a better understanding of the regulatory mechanisms mediated by p85, and may facilitate the development of future drugs targeting the PI3K pathway. Citation Format: Evan T. Brower, Sandra B. Gabelli, Qing Wang, Raghothama Chaerkady, Christopher E. Berndsen, Robert N. Cole, Jonathan M. Backer, Mathias Schäfer, Andrea Sinz, Kenneth W. Kinzler, Bert Vogelstein, L. Mario Amzel. The molecular architecture of p85α as determined by SAXS and chemical cross-linking. [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 2225. doi:10.1158/1538-7445.AM2013-2225
Methionine Metabolism Regulates Maintenance and Differentiation of Human Pluripotent Stem Cells
Authors: Nobuaki Shiraki, Yasuko Shiraki, Tomonori Tsuyama, Fumiaki Obata, Masayuki Miura, Genta Nagae, Hiroyuki Aburatani, Kazuhiko Kume, Fumio Endo, Shoen Kume
Journal: Cell Metabolism (2014)
Effect of intraluminal application of tissue-type plasminogen activator on the fibrinolytic activity of experimental vein grafts
Authors: M. J Underwood, G. Cooper, R. More, A. Coumbe, C. Toner, P. Reynolds, D. de Bono
Journal: Cardiovascular Research (1995)

The aim was to quantify the effect of intraluminally applied tissue-type plasminogen activator (tPA) on the fibrinolytic activity of experimental vein grafts and assess the effect of pretreatment of the vein on early platelet and thrombus formation using histological techniques.A pig model of bilateral saphenous venin-carotid artery grafts was used. In each animal one side of the neck was grafted using vein distended to 230 mm Hg and pretreated with tPA (1 mg.ml-1) for a period of 15 min before grafting (treated graft). The perfused in situ for 2 h after implantation and before analysis. Changes in local fibrinolytic activity were quantified using fibrin plate techniques and specific chromogenic assays for tPA and urokinase (uPA) in tissue extract (n = 6 animals). Histological assessment was made using light and scanning microscopy (n = 4 animals).Surgical preparation and distention significantly reduced the fibrinolytic activity of pig saphenous vein in terms of areas of lysis produced on fibrin plates (P < 0.05), tPA activity (P < 0.05), and uPA activity (P < 0.05). Pretreatment of distended vein with tPA before grafting significantly enhanced its fibrinolytic activity after 2 h perfusion compared to control (untreated) grafts, as assessed by areas of lysis on fibrin plates (P < 0.05) and specific tPA activity (P < 0.05). Treated grafts also showed qualitatively less platelet and thrombus formation on histological examination.Pretreatment of surgically harvested vein by intraluminal application of tPA before grafting enhances its fibrinolytic activity after exposure to 2 h perfusion in vivo. This technique requires further investigation to validate its potential as a means of providing local anticoagulation to veins implanted as arterial grafts thereby reducing the incidence of early graft thrombosis.
Use of Antipsychotic and Antidepressant Drugs by Chronically Ill Patients
Authors: THOMAS A. McCLELLAN, GARY COWAN
Journal: American Journal of Psychiatry (1970)

Of the patients in a VA mental hygiene clinic, 81 percent receiving antipsychotic and antidepressant drugs were studied as to their use of medication and the extent to which they accurately reported their use. The authors found that a small number were not taking any of the medication, that a substantial number were taking amounts significantly less than that prescribed, and that these patients were not volunteering this information to their therapist.
The pulmonary macrophage.
Authors: D H Bowden
Journal: Environmental Health Perspectives (1976)

An overview of the pulmonary macrophage is provided, with particular emphasis on the origin of this cell and the adaptive mechanisms whereby the macrophagic system is able to respond to increased inhalant loads of organic and inorganic pollutants. Evidence is presented which favors an hematopoietic origin for the alveolar macrophage with a monocytic transportation compartment in the blood and an interstitial cell compartment in the lung in which cellular division and maturation may occur. Through the simple mechanism of increased cellular turnover this system of mononuclear phagocytes rapidly adapts to most inhalant challenges. In addition to its primary tasks phagocyte and destroyer of microorganisms the macrophage plays a pivotal role in the genesis of silicotic fibrosis, and it is possible that similar mechanisms may hold for a variety of cryptogenic fibroses. Paradoxically, destruction of collagen by the dual mechanisms of phagocytosis and the secretion of lytic enzymes may also occur. The relevance of this secretory function of the macrophage to the pathogenesis of destructive diseases of the lung such as emphysema remains to be determined.
Transgenic mice expressing the human heat shock protein 70 have improved post-ischemic myocardial recovery.
Authors: J C Plumier, B M Ross, R W Currie, C E Angelidis, H Kazlaris, G Kollias, G N Pagoulatos
Journal: Journal of Clinical Investigation (1995)

Heat shock treatment induces expression of several heat shock proteins and subsequent post-ischemic myocardial protection. Correlations exist between the degree of stress used to induce the heat shock proteins, the amount of the inducible heat shock protein 70 (HSP70) and the level of myocardial protection. The inducible HSP70 has also been shown to be protective in transfected myogenic cells. Here we examined the role of human inducible HSP70 in transgenic mouse hearts. Overexpression of the human HSP70 does not appear to affect normal protein synthesis or the stress response in transgenic mice compared with nontransgenic mice. After 30 min of ischemia, upon reperfusion, transgenic hearts versus nontransgenic hearts showed significantly improved recovery of contractile force (0.35 +/- 0.08 versus 0.16 +/- 0.05 g, respectively, P < 0.05), rate of contraction, and rate of relaxation. Creatine kinase, an indicator of cellular injury, was released at a high level (67.7 +/- 23.0 U/ml) upon reperfusion from nontransgenic hearts, but not transgenic hearts (1.6 +/- 0.8 U/ml). We conclude that high level constitutive expression of the human inducible HSP70 plays a direct role in the protection of the myocardium from ischemia and reperfusion injury.
The induction of macrophage hemeoxygenase-1 is protective during acute kidney injury in aging mice
Authors: David A. Ferenbach, Noemie C.J. Nkejabega, Jennifer McKay, Abhijeet K. Choudhary, Madeleine A. Vernon, Matthew F. Beesley, Spike Clay, Bryan C. Conway, Lorna P. Marson, David C. Kluth, Jeremy Hughes
Journal: Kidney International (2011)
Stem Cell Transplantation for Hematologic Malignancies
Authors: Camille N. Abboud
Journal: Annals of Internal Medicine (2004)

Medical Writings: Book Notes7 September 2004Stem Cell Transplantation for Hematologic MalignanciesCamille N. Abboud, MDCamille N. Abboud, MDFrom James P. Wilmot Cancer Center, University of Rochester Medical School, Rochester, New York.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-5-200409070-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Soiffer RJ, ed. 482 pages. Totowa, NJ: Humana Pr; 2004. $155.00. ISBN 1588291804. Order phone 973-256-1699.Field of medicine: Stem-cell transplantation.Format: Hardcover book.Audience: Hematologists–oncologists and fellows and allied personnel involved in transplantation.Purpose: To summarize the current state-of-the-art and a vision into future advances in stem-cell transplantation.Content: Part I describes indications for stem-cell transplantation in hematologic malignant conditions and breast cancer. Part II details complications of transplantation: acute and chronic graft-versus-host disease, hepatic veno-occlusive disease and lung injury, immune reconstitution, infections, Epstein–Barr virus lymphoproliferative disease, and quality-of-life issues after transplantation. Part III describes sources of stem cells ... Author, Article, and Disclosure InformationAffiliations: From James P. Wilmot Cancer Center, University of Rochester Medical School, Rochester, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 September 2004Volume 141, Issue 5Page: 412KeywordsBreast cancerHematologic malignanciesLung transplantationLymphocytesMultiple myelomaSoftware toolsStem cell transplantationStem cellsTransplantationVision ePublished: 7 September 2004 Issue Published: 7 September 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Renal histology in ANCA-associated vasculitis: Differences between diagnostic and serologic subgroups
Authors: Herbert A. Hauer, Ingeborg M. Bajema, Hans C. Van Houwelingen, Franco Ferrario, Laure-Hélène Noël, Rüdiger Waldherr, David R.W. Jayne, Niels Rasmussen, Jan A. Bruijn, E. Christiaan Hagen
Journal: Kidney International (2002)
Localization of aggregated cell surface antigens of target cells bound to cytotoxic T lymphocytes.
Authors: G Berke, Z V Fishelson
Journal: The Journal of Experimental Medicine (1975)

The redistribution of aggregated cell surface antigens of target cells bound to cytotoxic T lymphocytes was investigated. It was found that cap formation induced by antibody always occurred toward the site of binding. It is suggested that the polar localization of capped target cell surface determinants is a consequence of cytotoxic T-lymphocyte target cell interaction.
Jarid2 regulates hematopoietic stem cell function by acting with polycomb repressive complex 2
Authors: Sarah A. Kinkel, Roman Galeev, Christoffer Flensburg, Andrew Keniry, Kelsey Breslin, Omer Gilan, Stanley Lee, Joy Liu, Kelan Chen, Linden J. Gearing, Darcy L. Moore, Warren S. Alexander, Mark Dawson, Ian J. Majewski, Alicia Oshlack, Jonas Larsson, Marnie E. Blewitt
Journal: Blood (2015)
The Rational Clinical Examination
Authors: Joseph M. Scheller
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Dr Sackett<sup>1</sup>is to be commended for his statistical approach to the problems of clinical diagnosis. I hope that this type of logic becomes more popular among physicians. One reason that this type of thinking has not yet taken hold may be because of physicians' fears of liability when they rely on clinical judgment and not on test results. For example, in the case of possible ascites in an alcoholic patient cited by Sackett, if a physician is 90% sure that the patient does not have ascites based on his clinical acumen and does not order a confirmatory test, he may be held accountable for complications of that problem if his diagnosis is wrong. On the other hand, he will never be criticized (except perhaps in Sackett's teaching program) or sued for obtaining an abdominal ultrasonogram. Another problem I have with Sackett's calculations is with the
Incidence of self poisoning in patients prescribed psychotropic drugs.
Authors: K Skegg, D C Skegg, S M Richards
Journal: BMJ (1983)

The drugs most commonly used in self poisoning are the psychotropics, but the proportion of patients given these drugs who take overdoses is unknown. In a prospective study of 43117 people in Oxfordshire, prescriptions issued by general practitioners were linked with records of hospital admissions and deaths. During two years there were 79 episodes of deliberate self poisoning leading to hospital admission or death. The number of patients who took overdoses of psychotropic drugs was small in relation to the total number prescribed such drugs. Of 5600 people aged 10 or older who received psychotropic drugs during one year, 17 (3.0 per 1000) poisoned themselves with these drugs within 12 months. The rate of self poisoning with psychotropic drugs declined significantly with increasing age (p less than 0.001). Almost three quarters of the patients who took overdoses of prescribed psychotropics received further psychotropic drugs during the three months after their admission to hospital.
Automobile Child Seating Systems
Authors: William F. Rowley
Journal: JAMA (1971)

<h3>To the Editor.—</h3> I would like to call your readers' attention to the effective date of the Motor Vehicle Safety Standard No. 213, Child Seating Systems, which is April 1, 1971 (<i>Fed Register</i><b>35:</b>14759-14821, 1970). This ruling provides that child seating systems offered for sale have to meet specifications set by the National Highway Traffic Safety Administration. Now, for the first time, a physician, who can and should recommend that parents of young children purchase restraining devices, can be assured that these devices will provide effective restraint. However, the safety seats will work<i>only if the instructions are followed</i>; these<i>always</i>include the use of a vehicle seat belt. Prior to this, many so-called child-car seats were not only inadequate, but at times were worse than nothing. The physician should inform parents that they should buy devices labelled as meeting the specifications which take effect April 1, 1971, or
The Cause of Death
Authors: Walter I. Hofman
Journal: JAMA (1974)

To the Editor.—  The causes of  listed in three of the four cases cited in the editorial are all complications of the underlying disease entity or problem. Although the  certificates in almost all states say   due  due to, the physician is not obligated to fill in the cause of  in that manner. Many of us would issue case 1 as a type of hip fracture with complicating pulmonary embolism, and case 4 as intravenous narcotism or narcotic addiction with complicating endocarditis, etc. Dr. Hussey's premises for the true cause of death are the factors leading up  or circumstances surrounding, the cause of death. These are stated in the  certificate under the item How did injury occur? Further, the circumstances surrounding  are an integral part of the opinion written for any medicolegal problems, including autopsy.  The editorial should serve one purpose, namely,
A retinoic acid–dependent network in the foregut controls formation of the mouse lung primordium
Authors: Felicia Chen, Yuxia Cao, Jun Qian, Fengzhi Shao, Karen Niederreither, Wellington V. Cardoso
Journal: Journal of Clinical Investigation (2010)

The developmental abnormalities associated with disruption of signaling by retinoic acid (RA), the biologically active form of vitamin A, have been known for decades from studies in animal models and humans. These include defects in the respiratory system, such as lung hypoplasia and agenesis. However, the molecular events controlled by RA that lead to formation of the lung primordium from the primitive foregut remain unclear. Here, we present evidence that endogenous RA acts as a major regulatory signal integrating Wnt and Tgfbeta pathways in the control of Fgf10 expression during induction of the mouse primordial lung. We demonstrated that activation of Wnt signaling required for lung formation was dependent on local repression of its antagonist, Dickkopf homolog 1 (Dkk1), by endogenous RA. Moreover, we showed that simultaneously activating Wnt and repressing Tgfbeta allowed induction of both lung buds in RA-deficient foreguts. The data in this study suggest that disruption of Wnt/Tgfbeta/Fgf10 interactions represents the molecular basis for the classically reported failure to form lung buds in vitamin A deficiency.
Cerebral Whipple's Disease with Negative Jejunal Histology
Authors: Gerhard E. Feurle, Benedikt Volk, Rüdiger Waldherr
Journal: New England Journal of Medicine (1979)

ORGANIC psychosyndromes, paralysis of gaze, nystagmus and myoclonus may dominate the clinical appearance of Whipple's disease.1 2 3 The basis for these signs is infiltration of the cerebral gray matter by sickle-particle-containing (SPC) cells, as described by Sieracki4 and reviewed by others.1 2 3 Current observation of two patients has now revealed that Whipple's disease may also present itself with hypothalamic symptoms, which may even progress when there is no apparent involvement of the small intestine.Case ReportsCase 1. The clinical course of this patient has been reported up to 1975.1 Under treatment with penicillin, streptomycin, chloramphenicol and tetracycline, his arthritis, confusional states, . . .
A delivery system specifically approaching bone resorption surfaces to facilitate therapeutic modulation of microRNAs in osteoclasts
Authors: Jin Liu, Lei Dang, Defang Li, Chao Liang, Xiaojuan He, Heng Wu, Airong Qian, Zhijun Yang, Doris W.T. Au, Michael W.L. Chiang, Bao-Ting Zhang, Quanbin Han, Kevin K.M. Yue, Hongqi Zhang, Changwei Lv, Xiaohua Pan, Jiake Xu, Zhaoxiang Bian, Peng Shang, Weihong Tan, Zicai Liang, Baosheng Guo, Aiping Lu, Ge Zhang
Journal: Biomaterials (2015)
Withdrawal of Diazepam
Authors: Bernadine Z. Paulshock
Journal: JAMA (1976)

<h3>To the Editor.—</h3> I have read with interest and concern the report (233:135, 1975) concerning the observation that patients who have taken diazepam in moderate doses suffer symptoms such as "trembling, agitation, fearfulness, stomach cramps, and sweating" but not major reactions, such as convulsions, when diazepam is withdrawn. It seems to me that this constellation of symptoms is compatible with symptoms of anxiety, ultimately relieved when the patient is within the protective confines of a psychiatric institution, as I believe these patients were. It seems reasonable to me that symptoms in a patient with anxiety moderately or markedly relieved by diazepam might worsen without it, but the patient's condition might then improve in a hospital milieu. The fact that this group of patients did not respond to tricyclics strengthens my belief that the prime diagnosis in this group may have been anxiety relieved by diazepam, rather than a manifestation of