tbuckley/cabot-search huggingface dataset:
Urinary Concentrating Mechanism: Structure and Function
Authors: George Dunea
Journal: JAMA (1982)

This book, written jointly by an American physiologist and a German anatomist, presents a detailed account of the structure and function of the renal medulla, with particular emphasis on the manner in which the kidney elaborates a concentrated urine. It is a scholarly book, and the authors introduce their complicated subject by likening it to a Gothic cathedral. They remind us that what, in its completed, seemingly superhuman form, fills us with wonder and admiration was in fact built over many years, section by section, by the toil of ordinary, and often profane, human laborers. Our knowledge of the countercurrent mechanism is likewise being advanced by scientists erecting an elaborate scaffolding of new information and ingenious hypotheses without being able to visualize clearly what the cathedral will look like in its complete form. But John Ruskin, by no means a stranger to cathedrals, might have also compared this book to
The Place of Chemotherapy in Management
Authors: John Hadfield
Journal: JAMA (1967)

Chemotherapy is not specific. It differs fundamentally from hormone therapy which is directly dependent on the hormone sensitivity of the tumor. This lack of specificity depresses the mitotic activity of all rapidly multiplying normal cells such as those of the hemopoietic bone marrow and the epithelium of the gastrointestinal tract. The magnitude of this antimitotic activity on normal cells can be serious and is often unpredictable. The choice of methods of administration is dictated by the widespread nature of the disease. Isolated perfusion for recurrence in the breast area or a previously untreated primary lesion is of little value, as there is no major cannulable arterial supply to the breast and innominate or subclavian cannulation<sup>21</sup>is even too localized for the distribution of the disease. It might, however, be an adjunct to parenteral therapy when there is a concentration of metastases at a site or in an organ with
Synergistic antileukemic effects between ABT-869 and chemotherapy involve downregulation of cell cycle-regulated genes and c-Mos-mediated MAPK pathway
Authors: Zhou J, Pan M, Xie Z, Loh Sl, Bi C, Tai Yc, Lilly M, Lim Yp, Han Jh, Glaser Kb, Albert Dh, Davidsen Sk, Chen Cs
Journal: Leukemia (2007)
A Systems Analysis of Mitotic Apparatus Inhibitors Defines a Response Network for Breast Cancer.
Authors: Z. Hu, J. Mao, G. Huang, W. Kuo, M. Lenburg, S. Ziyad, J. Korkola, N. Bayani, N. Wang, S. Gu, B. Weber, R. Wooster, J. Gray
Journal: Cancer Research (2009)

Abstract Deregulation of aspects of the mitotic apparatus leads to increased genome instability, carcinogenesis and aggressive tumor behavior in human and rodent model systems1. This knowledge has stimulated development of inhibitors of elements of the mitotic apparatus as anticancer agents including PLK1, CENPE, and AURKB and several are now being tested for efficacy clincially2-6. These trials and eventual clinical use will benefit from molecular markers that predict response. In order to identify such markers, we assessed quantitative responses to the agents GSK461364, GSK923295 and GSK1070916 that target PLK1, CENPE and AURKB; respectively, in a panel of 50 breast cancer cell lines. This analysis showed that basal subtype cell lines were preferentially sensitive to all three agents and that responses among the lines to the three agents were strongly correlated. This may be explained by our discovery that components of the mitotic apparatus including PLK1, CENPE and AURKB form a transcriptionally co-regulated network comprised of more than 50 genes that is preferentially active in basal subtype of breast cell lines and primary tumors. Remarkably, this network also is activate in subsets of cancers of the lung, ovarian, prostate and brain, Wilms tumor, human blood malignancies and selected normal tissues. We then defined a mitotic apparatus network index (MANI) and showed that high MANI was associated with poor outcome clinically and with preferential responsive to GSK461364, GSK923295 and GSK1070916 in preclinical models. This suggests that measures of the MANI will identify poor outcome tumors that will likely respond well to mitotic apparatus network gene inhibitors as well as potential dose limiting normal tissues.Reference1. Quigley, D.A. et al. Nature 458, 505-8 (2009).2. Strebhardt, K. &amp; Ullrich, A. Nat. Rev. Cancer 6, 321-330 (2006).3. Toyoshima-Morimoto, F., Taniguchi, E., Shinya, N., Iwamatsu, A. &amp; Nishida, E. Nature 410, 215-20 (2001).4. Barr, F.A., Sillje, H.H. &amp; Nigg, E.A. Nat. Rev. Mol. Cell. Biol. 5, 429–440 (2004).5. McInnes, C. et al. Nat. Chem. Biol. 2, 608–617 (2006).6. Yamada, S. et al. Oncogene 23, 5901-5911(2004). Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2020.
Chromatographic Evidence of Polychlorinated Biphenyl Exposure From a Spill
Authors: Walter J. Rogan
Journal: JAMA (1983)

Women who were part of a study in which polychlorinated biphenyls (PCBs) were measured in breast milk were exposed accidentally to a PCB spill. While the overall level of PCBs found in their milk was not different from background levels, the chromatograms showed unusual peaks that indicate the presence of heavily chlorinated PCBs of the kind that were spilled.
In Search of Adrenocortical Stem and Progenitor Cells
Authors: Alex C. Kim, Ferdous M. Barlaskar, Joanne H. Heaton, Tobias Else, Victoria R. Kelly, Kenneth T. Krill, Joshua O. Scheys, Derek P. Simon, Alessia Trovato, Wei-Hsiung Yang, Gary D. Hammer
Journal: Endocrine Reviews (2009)

Scientists have long hypothesized the existence of tissue-specific (somatic) stem cells and have searched for their location in different organs. The theory that adrenocortical organ homeostasis is maintained by undifferentiated stem or progenitor cells can be traced back nearly a century. Similar to other organ systems, it is widely believed that these rare cells of the adrenal cortex remain relatively undifferentiated and quiescent until needed to replenish the organ, at which time they undergo proliferation and terminal differentiation. Historical studies examining cell cycle activation by label retention assays and regenerative potential by organ transplantation experiments suggested that the adrenocortical progenitors reside in the outer periphery of the adrenal gland. Over the past decade, the Hammer laboratory, building on this hypothesis and these observations, has endeavored to understand the mechanisms of adrenocortical development and organ maintenance. In this review, we summarize the current knowledge of adrenal organogenesis. We present evidence for the existence and location of adrenocortical stem/progenitor cells and their potential contribution to adrenocortical carcinomas. Data described herein come primarily from studies conducted in the Hammer laboratory with incorporation of important related studies from other investigators. Together, the work provides a framework for the emerging somatic stem cell field as it relates to the adrenal gland.
Polyp as a Complication of Argon Plasma Coagulation in Watermelon Stomach
Authors: S. Izquierdo, E. Rey, A. Gutiérrez del Olmo, C. Almansa, J. Andrés Ramírez Armengol, M. Díaz-Rubio
Journal: Endoscopy (2005)

Gastric antral vascular ectasia (GAVE), or watermelon stomach, is an uncommon cause of gastrointestinal blood loss and iron-deficiency anaemia, that usually requires periodic blood transfusions. Endoscopic treatments, including endoscopic sclerotherapy, coagulation with Nd:YAG and argon lasers, argon plasma coagulation (APC), heater probe therapy, cryotherapy, and monopolar and multipolar electrocoagulation, are now the approaches of choice [1]. They are effective and safe, reducing transfusion requirements in these patients, although some complications have been reported [2] [3] [4].
Abstract 5780: Development of potent inhibitors of the DNA-dependent protein kinase (DNA-PK)
Authors: Celine Cano, Chris Bailey, Julia Bardos, Nicola Curtin, Mark Frigerio, Bernard Golding, Ian Hardcastle, Marc Hummersone, Keith Menear, David Newell, Kappusamy Saravanan, K Shea, Graeme Smith, Roger Griffin
Journal: Cancer Research (2010)

Abstract The cellular response to DNA double-strand break (DSB) formation is an essential component of normal cell survival, following exposure to DNA-damaging chemicals and ionising radiation. The serine/threonine kinase DNA-dependent protein kinase (DNA-PK) is a member of the phosphatidylinositol (PI) 3-kinase related kinase (PIKK) family of enzymes, and plays an important role in DNA DSB repair via the non-homologous end-joining (NHEJ) pathway. DNA-PK inhibitors may, therefore, be useful as agents to improve the activity of radio- and chemo-therapy in the treatment of cancer. Identification of the lead benzo[h]chromen-4-one DNA-PK inhibitor NU7026 (IC50 = 0.23 uM) guided the development of the potent and selective ATP-competitive chromenone NU7441 (DNA-PK IC50 = 30 nM). Structure-activity relationship studies for DNA-PK inhibition by chromenone-derivatives were conducted in conjunction with homology modelling. Library synthesis was undertaken employing a solution multiple-parallel approach, by O-alkylation or N-acylation of the appropriately substituted NU7441 derivatives, respectively, followed by reaction with a range of amines to afford the target compounds. These studies resulted in the identification of the highly potent inhibitor KU-0060648 (IC50 = 8.6 nM). The further development of KU-0060648 and analogues will be described. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5780.
Postmenopausal Estrogens and Risk of Myocardial Infarction in Diabetic Women
Authors: Robert C Kaplan, Susan R Heckbert, Noel S Weiss, Patricia W Wahl, Nicholas L Smith, Katherine M Newton, Bruce M Psaty
Journal: Diabetes Care (1998)

OBJECTIVE The effect of hormone replacement therapy on the risk of myocardial infarction in diabetic women has not been well studied. We conducted a case-control study of postmenopausal estrogen use and risk of incident myocardial infarction (MI) in pharmacologically treated diabetic women enrolled at Group Health Cooperative of Puget Sound, a large health maintenance organization in the state of Washington. RESEARCH DESIGN AND METHODS Case subjects (n = 212) were all postmenopausal women with treated diabetes who sustained an incident fatal or nonfatal MI between July 1986 and December 1994. Control subjects (n = 122) were treated diabetic women drawn from a stratified random sample of postmenopausal women without prior MI. Computerized pharmacy data and medical records were used to measure use of estrogens. Cardiovascular risk factors recorded from medical records, computerized pharmacy and laboratory data, and telephone interviews were used as adjustment variables. RESULTS In this study, 8.5% of case and 13.9% of control subjects were current users of estrogens. The relative risk (RR) of MI for current estrogen users was 0.51 (95% CI 0.22–1.15) relative to never users, adjusted for age, study year, weight, angina, and duration of treated diabetes. Among current estrogen users, risk of MI tended to decline with each additional year of estrogen use (adjusted RR – 0.78, 95% CI 0.56–1.08). Of those studied, 45.3% of case and 37.7% of control subjects were past users of estrogens (adjusted RR = 1.22,95% CI 0.71–2.09). CONCLUSIONS This study suggests that use of postmenopausal estrogens does not increase risk of MI in diabetic women and that sustained use may be of benefit.
Molecular Biology and Viral Pathogenesis: Clinical Spinoff
Authors: Abner Louis Notkins
Journal: New England Journal of Medicine (1985)

Why does one virus produce neurologic disease, another liver disease, and still another the common cold? The answer to this and other questions is coming from both classic studies on viral pathogenesis and the new tools of molecular biology.1 The information being generated is changing our approach to the diagnosis, treatment, and prevention of viral diseases.In this issue of the Journal, Carson et al. describe ciliary defects in the nasal epithelium of children with acute viral respiratory infections.2 Functionally intact cilia in the upper respiratory tract are required for the clearance of secretions, debris, and foreign particles. Normal . . .
GATA2 is Epigenetically Repressed in Human and Mouse Lung Tumors and Is Not Requisite for Survival of KRAS Mutant Lung Cancer
Authors: Mathewos Tessema, Christin M. Yingling, Amanda M. Snider, Kieu Do, Daniel E. Juri, Maria A. Picchi, Xiequn Zhang, Yushi Liu, Shuguang Leng, Carmen S. Tellez, Steven A. Belinsky
Journal: Journal of Thoracic Oncology (2014)
Treatment of experimental renal osteodystrophy with pamidronate
Authors: Jarkko Jokihaara, Ilkka H. Pörsti, Peeter Kööbi, Pasi M. Jolma, Jukka T. Mustonen, Heikki H.T. Saha, Harri Sievänen, Pekka Kannus, Urszula T. Iwaniec, Russell T. Turner, Teppo L.N. Järvinen
Journal: Kidney International (2008)
Abstract 1512: Role of Epstein-Barr virus in nasopharyngeal carcinoma under metabolic stress.
Authors: VMY Lau, SW Tsao
Journal: Cancer Research (2013)

Abstract Most nasopharyngeal carcinoma (NPC) biopsies contain a human pathogen named as Epstein-Barr virus (EBV). EBV infection is considered as an early event involved in the pathogenesis of NPC. However, the close association of EBV with NPC is a paradox. EBV infection is common that occurs in ≥95% of the world's population, yet the incidence rate of NPC is rare worldwide and is only seen in Cantonese speaking ethnic groups in Southern Asia. The mechanisms that regulate EBV infection of NPC/pre-malignant NP cells including the events involved in latency and lytic activation (either in vitro or in vivo) are not well-defined. Expressions of latent and lytic EBV genes have been shown to have variable effects on the biology and malignant properties of EBV-infected cells. Hypoxia and nutrient-starvation are common physiological stresses within tumours and may have impact on regulation of latent and lytic EBV infection in NPC cells. Here we report that the levels of hypoxia-inducible factor, HIF-1α protein, a prime hypoxic-stress responsive marker for mammalian cells, are higher in EBV-infected NPC/pre-malignant NP cell lines under hypoxia than their non-infected counterparts, which may imply an enhanced survival ability of EBV-infected NP cells. The alteration in gene expression profiles of host cells and expression of EBV genes observed in infected cells may be responsible for the stabilization of HIF-1α and vice versa. Moreover, EBV infection enhances the tumour growth rate and size of NPC cells xenografts in nude mice. The main stem of this study is to examine whether there is a differential response between EBV-infected and non-infected NP cells towards various metabolic stresses. Through studying this project, the mechanism and function of HIF-1α stability by EBV infection will be explored, which is expected to help characterizing the role of EBV in transformation of epithelial cells and how EBV infection may enhance NPC cells to survive inside a tumour core. Citation Format: VMY Lau, SW Tsao. Role of Epstein-Barr virus in nasopharyngeal carcinoma under metabolic stress. [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 1512. doi:10.1158/1538-7445.AM2013-1512 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Aspirin and Diabetic Retinopathy
Authors: Hugh H. Hussey
Journal: JAMA (1974)

Kwaan and his co-workers, 1 having previously observed a diabetic patient with disseminated intravascular coagulation consequent to increased platelet aggregation, had studied 87 other mature-onset diabetic subjects of whom 77 exhibited platelet aggregation-enhancing activity. The degree of such activity did not correlate with plasma levels of lipoproteins, triglycerides, free fatty acids, the free fatty acids to albumin molar ratio, or such complications as occlusive diseases of large arteries and neuropathy. However, there was distinct correlation with the occurrence of diabetic nephropathy, retinopathy, and the duration of the disease.  More recently, as a follow-up to their earlier observations, the same group of authors 2 conducted further studies of the correlation of platelet aggregation-enhancing activity with diabetic retinopathy. The method for measuring the degree of activity permitted expression of an aggregation index (AI).  In diabetic patients without retinopathy or with early retinopathy, a percentage increase of AI was lacking or slight, and
Postoperative Ulnar Neuropathy
Authors: Richard P. Strader
Journal: JAMA (1980)

<h3>To the Editor.—</h3> I was disappointed when, at the close of the article by Miller and Camp, "Postoperative Ulnar Neuropathy" (242:1636, 1979), they mention only the operating room table and its hardware as possible culprits in the cubital tunnel syndrome. A far more common hard object, the anesthetist's stethoscope head, is often taped, strapped, or otherwise pressed into the cubital fossa, after which, a series of perhaps 50 blood pressure readings are taken in a typical four-hour surgery. Surely this study should have correlated location of the blood pressure cuff and stethoscope head with the lateralization of ulnar neuropathies. These data are easily incorporated into the anesthesia form.
Identifying patients with ischaemic heart disease in general practice: cross sectional study of paper and computerised medical records
Authors: J. Gray, A. Majeed, S. Kerry, G. Rowlands
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To identify patients with ischaemic heart disease by using a practice computer and to estimate the work required to do so. <b>Design:</b> Cross sectional study. Data from the notes and from the computer records of 1680 patients were used to build a database. This was used to compare different methods of identifying patients with ischaemic heart disease. <b>Setting:</b> 11 general practices in the Battersea primary care group in south London. <b>Subjects:</b> 1 in 40 random sample of patients aged 45 or older. <b>Main outcome measures:</b> Numbers of patients identified with ischaemic heart disease. <b>Results:</b> The combination of the Read code for ischaemic heart disease (G3) and a prescription for a nitrate had a 73% sensitivity and a yield (100/positive predictive value) of one case of ischaemic heart disease for every 1.2 sets of notes reviewed. By searching the records of patients also receiving aspirin, atenolol, digoxin, or a statin, the sensitivity was increased to 96% but the yield fell to one in three. <b>Conclusion:</b> Although commonly used to identify cases, a computer search for G3 code or nitrate missed almost 30% of patients with ischaemic heart disease. A substantially higher percentage of patients can be identified by adding other drugs to the search strategy.
Canadian doctor is released from jail but stopped from leaving Egypt
Authors: S. Arie
Journal: BMJ (2013)

A Canadian doctor and a filmmaker who were released from jail in Egypt after being held for more than six weeks without charge are being prevented from leaving the country.

The two men, who were arrested on 16 August amid street protests in Cairo,1 were released from jail on 6 October. But when they checked in for a flight to Germany they were not allowed to board. The Associated Press reported that …
NATIONAL QUARANTINE A REASONABLE FUNCTION OF THE GOVERNMENT.
Authors: L. SEXTON
Journal: JAMA (1906)

The preservation of the health of the people of the United States is a function, within the scope of the duty of the national government. It bears a close relationship to the efforts put forward by the national government toward preventing the spread of epidemic diseases and finds its counterpart in the methods adopted to prevent the destruction of forest trees in the New England states and the destruction of the fruit industry on the Pacific slope. The care of the health of its citizens, the keeping out of bubonic plague, Asiatic cholera, and yellow fever are certainly as important as carrying out the measures above mentioned, in which the government has undertaken control. The suggestions contained in this paper, which will be mostly in reference to yellow fever, will apply as well to bubonic plague in California, to Asiatic cholera in New York, or the isthmus of Panama. Every
Degenerative meniscus tears should be looked upon as wrinkles with age—and should be treated accordingly
Authors: May Arna Risberg
Journal: British Journal of Sports Medicine (2014)

We know that menisci play an important role in the knee. They contribute significantly to load bearing, load transmission and shock absorption across the joint and should, therefore, be preserved whenever possible. Furthermore, we have known for many years that meniscectomised knees develop osteoarthritis. We are also learning that not all meniscus injuries are the same. Acute tears, often occurring in adolescence and early adulthood, should be treated differently to degenerative tears in middle-aged patients. In fact, evidence suggests that, in the latter case, meniscus lesions are often merely an early sign of cartilage degeneration and osteoarthritis development.1

We have had a long history of treating meniscus tears with surgery without really having had any evidence if that was the best alternative treatment. …
Spleen cells from adult mice given total lymphoid irradiation or from newborn mice have similar regulatory effects in the mixed leukocyte reaction. I. Generation of antigen-specific suppressor cells in the mixed leukocyte reaction after the addition of spleen cells from adult mice given total lymphoid irradiation.
Authors: S Okada, S Strober
Journal: The Journal of Experimental Medicine (1982)

We added spleen cells from adult BALB/c mice treated with total lymphoid irradiation (TLI) to the mixed leukocyte reaction (MLR) using a variety of responder and stimulator cells. The spleen cells nonspecifically suppressed the uptake of [3H]-thymidine and the generation of cytolytic cells regardless of the responder-stimulator combination used. We also examined the effect of the spleen cells on the generation of antigen-nonspecific and antigen-specific suppressor cells in the MLR. The experimental results suggest that the spleen cells from TLI-treated mice inhibit the generation of nonspecific suppressor cells, but do not inhibit the generation of antigen-specific suppressor cells. Thus, alloantigenic stimulation of normal responder cells in vitro in the presence of spleen cells from TLI-treated mice generates large numbers of antigen-specific suppressor cells, but few cytolytic cells or nonspecific suppressor cells. Similar nonspecific inhibition of the MLR was observed with neonatal spleen cells. This in vitro system provides a regulatory model for the induction and maintenance of tolerance in vivo, in which adult mice given TLI or neonatal mice accept allogeneic bone marrow transplants without graft-vs.-host disease.
China pushes ahead with ban on indoor smoking
Authors: J. Parry
Journal: BMJ (2011)

China’s Ministry of Health has announced revisions to its guidelines on smoking in public places, banning smoking in indoor public places from 1 May. China ratified the World Health Organization’s Framework Convention on Tobacco Control in 2005 but missed the 9 January 2011 deadline to ban indoor smoking.

The move has been welcomed by tobacco control activists and public health experts. “This is a very significant move, as it comes from the central government. It’s a very important step to denormalise smoking and to protect people from the serious hazards of secondhand smoke,” said Tai-Hing Lam, head of the Department of Community Medicine at the University …