tbuckley/cabot-search huggingface dataset:
The telomerase inhibitor PinX1 is a major haploinsufficient tumor suppressor essential for chromosome stability in mice
Authors: Xiao Zhen Zhou, Pengyu Huang, Rong Shi, Tae Ho Lee, Gina Lu, Zhihong Zhang, Roderick Bronson, Kun Ping Lu
Journal: Journal of Clinical Investigation (2011)

Telomerase is activated in most human cancers and is critical for cancer cell growth. However, little is known about the significance of telomerase activation in chromosome instability and cancer initiation. The gene encoding the potent endogenous telomerase inhibitor PinX1 (PIN2/TRF1-interacting, telomerase inhibitor 1) is located at human chromosome 8p23, a region frequently exhibiting heterozygosity in many common human cancers, but the function or functions of PinX1 in development and tumorigenesis are unknown. Here we have shown that PinX1 is a haploinsufficient tumor suppressor essential for chromosome stability in mice. We found that PinX1 expression was reduced in most human breast cancer tissues and cell lines. Furthermore, PinX1 heterozygosity and PinX1 knockdown in mouse embryonic fibroblasts activated telomerase and led to concomitant telomerase-dependent chromosomal instability. Moreover, while PinX1-null mice were embryonic lethal, most PinX1+/– mice spontaneously developed malignant tumors with evidence of chromosome instability. Notably, most PinX1 mutant tumors were carcinomas and shared tissues of origin with human cancer types linked to 8p23. PinX1 knockout also shifted the tumor spectrum of p53 mutant mice from lymphoma toward epithelial carcinomas. Thus, PinX1 is a major haploinsufficient tumor suppressor essential for maintaining telomerase activity and chromosome stability. These findings uncover what we believe to be a novel role for PinX1 and telomerase in chromosome instability and cancer initiation and suggest that telomerase inhibition may be potentially used to treat cancers that overexpress telomerase.
Technology and the Allocation of Resources
Authors: M McGregor
Journal: New England Journal of Medicine (1989)

The health care systems of several Western democracies are widely perceived to be in a state of crisis. Each year the demand for health services increases, and it is more difficult to avoid a widening gap between the cost of these services and the amount that society is prepared to pay, through either the government or private third-party insurers. This is not a problem that will be solved simply.To explain why the costs of health services are so difficult to control, various reasons have been advanced — waste and inefficiency by health workers, clumsy and expensive bureaucratic systems, overconsumption . . .
16 Rhinitis of nasal polyps (P): Elevated epithelial metachromatic cell (MC) count is not related to allergy
Authors: J. Ruhno, M. Ohnisi, B. Anderssen, M. Vanzieleghem, M. Anderson, K. Howie, J. Denburg, J. Dolovich
Journal: Journal of Allergy and Clinical Immunology (1988)
Interferon and Herpes Zoster
Authors: Monto Ho
Journal: New England Journal of Medicine (1970)

Since the discovery of an unusual class of antiviral proteins, which Isaacs and Lindenmann called "interferon,"1 their role in the recovery from natural virus infections has been assumed but not clearly proved. Much of the evidence favoring such a role is circumstantial. For example, one finds interferon at the site of infection, or in the circulation, and assumes that it contributes to recovery. Conclusive evidence can only come if an experiment of nature or in the laboratory demonstrates an unfavorable course for virus infections in the absence of interferon but not of any other antiviral mechanism. As yet, no inborn . . .
Trends in Diagnoses of HIV Infection in the United States, 2002-2011
Authors: Anna Satcher Johnson, H. Irene Hall, Xiaohong Hu, Amy Lansky, David R. Holtgrave, Jonathan Mermin
Journal: JAMA (2014)

There has been increasing emphasis on care and treatment for persons with human immunodeficiency virus (HIV) in the United States during the past decade,, including the use of antiretroviral therapy for increasing survival and decreasing transmission. Accurate HIV diagnosis data recently became available for all states, allowing for the first time an examination of long-term national trends. These data can be used to monitor awareness of serostatus among persons living with HIV, primary prevention efforts, and testing initiatives. We examined trends in HIV diagnoses from 2002–2011 in the United States using data from the National HIV Surveillance System of the US Centers for Disease Control and Prevention (CDC).
Improved Accuracy in Predicting the Presence of Gleason Pattern 4/5 Prostate Cancer by Three-Dimensional 26-Core Systematic Biopsy
Authors: Noboru Numao, Satoru Kawakami, Minato Yokoyama, Junji Yonese, Chizuru Arisawa, Yuichi Ishikawa, Masao Ando, Iwao Fukui, Kazunori Kihara
Journal: European Urology (2007)
THE ASSOCIATION BETWEEN DRIVE TIME AND REPERFUSION THERAPY USE AMONG STEMI PATIENTS TRANSFERRED FROM A NON-PRIMARY PCI HOSPITAL: A REPORT FROM THE MISSION: LIFELINE PROGRAM
Authors: Amit Vora, DaJuanicia Holmes, Ivan Rokos, Matthew Roe, Christopher Granger, William French, Elliott Antman, Timothy Henry, Laine Thomas, Eric Bates, Tracy Wang
Journal: Journal of the American College of Cardiology (2013)
901-95 Stress-induced Subendocardial Underperfusion: A Potential Mechanism of Ischemia in Hypertrophic Cardiomyopathy (HCM)
Authors: Lubna Choudhury, Roberto Gistri, Mark Ryan, Franco Cecchi, William J. McKenna, Paolo G. Camici
Journal: Journal of the American College of Cardiology (1995)
A very breathless woman
Authors: C. Maybury, A. Horsley, R. Lord, R. Bright-Thomas
Journal: BMJ (2011)

A 37 year old woman was referred to the chest clinic by her general practitioner because of increasing shortness of breath over the previous few months and a chronic productive cough. She had no rhinitis or sinusitis. She gave a history of recurrent chest infections since early adulthood.

Other medical history of note included three episodes of pancreatitis, and as a baby she had a prolonged hospital admission with gastroenteritis and failure to thrive.

She lived with her son and worked as a kitchen assistant. She smoked 20 cigarettes a day and rarely drank alcohol. Her brother also had recurrent pancreatitis. She took no drugs.

On examination she was thin (body mass index 17). Her respiratory rate was 24 breaths/min, saturations were 95% on room air, and her blood pressure was 90/60 mm Hg. Respiratory examination showed clubbed fingers. Crackles were auscultated on the left with diminished breath sounds at the left base.

Blood tests showed haemoglobin 87 g/L (115-155), mean cell volume 85 fL (80-100), white cell count 16.3×109/L (4.5-11), platelets 765×109/L (130-400), and C reactive protein 857 nmol/L (0.76-28.5). On spirometry, her forced expiratory volume in one second was 0.9 L (38% of predicted) and forced vital capacity was 1.2 L. Her sputum was sent for microbiology and cultured Staphylococcus aureus and Haemophilus influenzae .

Chest radiography (fig 1⇓) and high resolution computed tomography (fig 2⇓) of the chest were performed.



Fig 1 Chest radiograph





Fig 2 High resolution computed tomogram of the chest





### 1 What are the radiological changes seen?

#### Short answer

The chest radiograph and high resolution computed tomogram show abnormalities consistent …
Cardiopulmonary Resuscitation: New Approaches
Authors: Jody Zylke
Journal: JAMA (1987)

MANY PHYSICIANS have heard of patients who, although they experienced a cardiac arrest, at least were fortunate enough to have persons trained in cardiopulmonary resuscitation (CPR) nearby and lifesaving equipment rapidly available. Now, an effort is under way to provide equipment and training that might offer that lifesaving  place, right time chance to many more victims of a witnessed arrest.  The key to this goal may be automatic external defibrillators that automatically analyze electrocardiographic signals. Richard O. Cummins, MD, and colleagues recently reported on their use by emergency medical technicians ( JAMA 1987;257:1605-1610). W. Douglas Weaver, MD, Leonard Cobb, MD, and associates have studied their use by first-responding firefighters ( Am J Cardiol 1986;57:1017-1021).  At an American Heart Association meeting in Monterey, Calif, Cummins, an assistant professor of medicine at the University of Washington, Seattle, discussed the rationale for also placing automatic external defibrillators in community settings for use by trained
Effect of oxidized lipids in the diet on oxidized lipid levels in postprandial serum chylomicrons of diabetic patients.
Authors: I Staprans, D A Hardman, X M Pan, K R Feingold
Journal: Diabetes Care (1999)

OBJECTIVE: To determine whether humans with type 2 diabetes have increased levels of oxidized fatty acids in their serum chylomicron fraction after the ingestion of dietary oxidized fatty acids. RESEARCH DESIGN AND METHODS: The study was performed on 31 male type 2 diabetic patients and 24 age-matched control subjects. Among the diabetic patients, 22 had poor glycemic control, defined as HbA1 &amp;gt; 10% (normal value &amp;lt; 7.7%). Nine patients had good glycemic control (HbA1 &amp;lt; or = 10). Heated corn oil containing low or high levels of oxidized fatty acids was used as a test meal. At 2.5 h after the test meal, 50-ml blood samples were obtained from all subjects, and the chylomicron fraction (Sf &amp;gt; 1,000) was isolated. The degree of oxidation in chylomicrons was determined by measuring conjugated dienes. For determining the postprandial levels of triglycerides and of oxidized lipids in serum chylomicrons over an extended time period, blood samples were obtained at 0, 2.5, 5.0, and 7.5 h for isolation of chylomicrons and determination of fatty acid oxidation. RESULTS: We found that at 2.5 h after the consumption of the test meal containing either a low or high oxidized fatty acid content, conjugated dienes in serum chylomicrons in diabetic subjects in poor glycemic control were increased compared with those in control subjects. Diabetic patients in good glycemic control had similar levels of oxidized lipid in their chylomicrons when compared with control subjects. Additionally, in diabetic patients in poor glycemic control, the levels of oxidized lipids in chylomicrons remained elevated for an extended post-prandial period. CONCLUSIONS: In diabetic subjects with poor glycemic control, dietary oxidized lipids induce an exaggerated and sustained increase in the levels of oxidized lipids in chylomicrons when compared with either control subjects or diabetic patients with good glycemic control. These increased postprandial levels of potentially atherogenic oxidized lipids may contribute to the accelerated atherosclerosis associated with diabetes.
Salvage peroral endoscopic myotomy for esophageal diverticulum
Authors: Hiroki Sato, Yuichi Sato, Manabu Takeuchi, Kazuya Takahashi, Shin-ryu Takeda, Haruhiro Inoue, Masaaki Kobayashi
Journal: Endoscopy (2015)

Esophageal diverticulum often causes secondary dysmotility. If a diverticulum associated with a functional disorder is growing and exacerbating symptoms, surgical treatment is usually indicated [1] [2]. Peroral endoscopic myotomy (POEM) was introduced by Inoue et al. in 2010 as a novel treatment technique for achalasia [3]. Here, we report our clinical experience of salvage POEM for esophageal diverticulum.
Inhibition of bicarbonate absorption by peptide hormones and cyclic adenosine monophosphate in rat medullary thick ascending limb.
Authors: D W Good
Journal: Journal of Clinical Investigation (1990)

In vitro microperfusion experiments were performed to examine the effects of peptide hormones on bicarbonate and ammonium transport by the medullary thick ascending limb (MTAL) of the rat. Arginine vasopressin (AVP; 2.8 X 10(-10) M in the bath) reduced bicarbonate absorption by 50% (from 7.8 to 3.7 pmol/min per mm). AVP caused a similar reduction in bicarbonate absorption in tubules perfused with 10(-4) M furosemide to inhibit net NaCl absorption. Glucagon (2 X 10(-9) M in the bath) also reduced bicarbonate absorption (from 11.7 to 7.6 pmol/min per mm). The inhibition of bicarbonate absorption could be reproduced with either exogenous 8-bromo-cAMP or forskolin. With 8-bromo-cAMP (10(-3) M) in the bath, addition of vasopressin to the bath did not significantly affect bicarbonate absorption. PTH significantly inhibited bicarbonate absorption, but the extent of inhibition was less than that observed with either AVP or glucagon. Vasopressin had no effect on net ammonium absorption in MTAL perfused and bathed with 4 mM NH4Cl. These findings indicate that: (a) vasopressin, glucagon, and PTH directly inhibit bicarbonate absorption in the MTAL of the rat; (b) this inhibition occurs independent of effects on net NaCl absorption and appears to be mediated in part by cAMP; and (c) HCO3- and NH4+ absorption can be regulated independently in the MTAL.
Abstract 3196: Antitumor effect of a Compound A, a derivative of a naturally occurring rotenoid deguelin, by inhibition of ATP binding to heat shock protein 90
Authors: Su-Chan Lee, Ju-Sung Lee, Seung-Yeob Hyun, Hoon Choi, Hongchan An, Kyu-Won Kim, Young-Ger Suh, Ho-Young Lee
Journal: Cancer Research (2014)

Abstract Despite several decades of intensive efforts to develop anti-cancer drugs and therapeutic strategies, lung cancer is still one of the main causes of cancer-related deaths worldwide. Deguelin, a natural plant product, has shown anti-cancer activities in skin, colon, breast and non-small cell lung (NSCLC) cancers. However, the potential side effects of deguelin could be an obstacle to its use in clinic. In the current study, we aimed to develop a derivative of deguelin with reduced potential side effects. We have synthesized a novel deguelin analog, compound A, and evaluated its effects on cancer and normal bronchial epithelial cell proliferation, survival, and colony formation by the MTT, FACS, and/or anchorage-dependent and -independent colony forming assays. Mechanisms underlying anti-tumor effects of compound A were investigated by Western blot, and RT-PCR. Treatment with compound A inhibited cancer cell proliferation and colony formation, promoted cell cycle arrest and induced apoptosis. Compound A also suppressed the expression of HIF-1α protein and its target gene, VEGF, in NSCLC cells. Administration of compound A to NSCLC xenograft-bearing mice significantly decreased tumor growth by inhibiting tumor angiogenesis and by inducing apoptosis. In its action mechanism, compound A was involved in binding to the ATP-binding pocket of HSP90, leading to the suppression of HSP90 function. These collective results suggest that a novel deguelin derivative, compound A, has a strong potential as an anti-cancer drug. Citation Format: Su-Chan Lee, Ju-Sung Lee, Seung-Yeob Hyun, Hoon Choi, Hongchan An, Kyu-Won Kim, Young-Ger Suh, Ho-Young Lee. Antitumor effect of a Compound A, a derivative of a naturally occurring rotenoid deguelin, by inhibition of ATP binding to heat shock protein 90. [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 3196. doi:10.1158/1538-7445.AM2014-3196
Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4/SDF-1
Authors: L Mirandola, L Apicella, M Colombo, Y Yu, D G Berta, N Platonova, E Lazzari, M Lancellotti, G Bulfamante, E Cobos, M Chiriva-Internati, R Chiaramonte
Journal: Leukemia (2013)
Book: 24-Hour Primary Care
Authors: M. B. Christensen, F. Olesen
Journal: BMJ (2000)

Eds Chris Salisbury, Jeremy Dale, Lesley Hallam ![Graphic][1]</img> Radcliffe Medical, £19.95, pp 248 ISBN 1 85775 311 9 Rating:![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> During the past few decades European general practice has been facing the dilemma of increasing public demand plus increasing general practitioner dissatisfaction with the heavy out of hours workload. As a consequence, many countries are debating the organisation of out of hours primary care that would be appropriate for both providers and consumers. With 24-Hour … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Interaction of capillary, interstitial, and lymphatic forces in the canine hindpaw.
Authors: H I Chen, H J Granger, A E Taylor
Journal: Circulation Research (1976)

We used plethysmograph techniques to measure or calculate the tissue and capillary forces and flows (capillary pressure, tissue and plasma oncotic pressure, transcapillary pressure drop, lymph flow, and interstitial pressure) in a dog hindpaw preparation in situ at three different venous pressures (PV). Since lymph was flowing from the preparation, an isovolumetric state represented an isofiltration state rather than the conventional isovolumetric or isogravimetric state. At an isofiltration capillary pressure of 12.8 mm Hg, lymph oncotic pressure averaged 3.8 mm Hg, plasma oncotic pressure averaged 20.9 mm Hg, and tissue pressure averaged -4.7 mm Hg (PV normal). The imbalance in transcapillary forces averaged 0.5 mm Hg and represented the lymph flow contribution (lymph flow/filtration coefficient) to maintainance of the normal isofiltration state. As isofiltration capillary pressure increased to 24.9 mm Hg, interstitial fluid volume increased by 1.7 ml/100g of tissue, tissue pressure rose by 4.6 mm Hg, lymph oncotic pressure fell by 2.2 mm Hg, and the transcapillary pressure drop increased to 5.6 mm Hg (PV = 20 mm Hg). At an isofiltration capillary pressure of 38.0 mm Hg, interstitial fluid volume increased by 17.5 ml/100g, interstitial pressure rose to +10 mm Hg, lymph oncotic pressure fell to 0.5 mm Hg, and the transcapillary pressure drop increased to 6.3 mm Hg (PV = 30 mm Hg). At moderate levels of PV elevation, the transcapillary pressure drop and increased tissue pressure provided 80% of the counterbalancing tissue force, each contributing approximately 40%. At higher venous pressures, the only tissue force that opposed filtration was an increase in tissue pressure.
Basic mechanisms of ovarian endocrine function
Authors: David W. Schomberg
Journal: Environmental Health Perspectives (1978)

This review outlines the current understanding of ovarian endocrine development and regulation with both physiological and biochemical background to provide a framework applicable to problems concerning environmental agents and ovarian endocrine function. Two approaches are used. First, the endocrine regulation of follicle development and corpus luteum function is considered in the classical sense, i.e., viewing these structures as gonadotropin-responsive units undergoing a programmed sequence of development and differentiation. Secondly, a relatively new area of ovarian physiology concerned with intra-ovarian regulation is explored, since this area holds potential for exploration of the direct effects of toxicological or environmental agents upon gonadal endocrine cells.
Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myélome (IFM)
Authors: Murielle Roussel, Philippe Moreau, Anne Huynh, Jean-Yves Mary, Clotaire Danho, Denis Caillot, Cyrille Hulin, Christophe Fruchart, Gérald Marit, Brigitte Pégourié, Pascal Lenain, Carla Araujo, Brigitte Kolb, Edouard Randriamalala, Bruno Royer, Anne-Marie Stoppa, Mammoun Dib, Véronique Dorvaux, Laurent Garderet, Claire Mathiot, Hervé Avet-Loiseau, Jean-Luc Harousseau, Michel Attal
Journal: Blood (2009)
Extreme Gigantism
Authors: William H. Daughaday
Journal: New England Journal of Medicine (1977)

The case of pituitary gigantism presented below was previously reported from this hospital by Behrens and Barr.1 An unauthorized partial report of the medical history up until the age of 18 years and three months was made by Humberd.2 Because of controversy resulting from this publication Drs. C. M. MacBryde and Cecil Charles were deterred from a definitive scientific report of their measurements and clinical observations on this extraordinary giant. It seems appropriate to present these measurements of growth velocity now and to suggest the nature of the severe and progressive neuropathy that eventually predisposed him to the infection and . . .
Junior doctors' working practices
Authors: P. R Burn
Journal: BMJ (1992)

care, the number of patients who are assigned to aggressive ambition and hence loses many with the government have offered the following, which generalists is far lower than the number Marsh more caring qualities, an emphasis that the women is what every junior doctor wants?proposes.Thus Marsh's statement that what in our care would doubtless reverse.In addressing(1) Non-medical staff trained to carry out should be done can be done in half the number of these problems the college must clarify its attitude phlebotomy, intravenous drug administration, visits is not supported by the American experience, to research and ensure that training can be electrocardiography, portering, and routine We have half the number of visits, twice the cost completed within the NHS.clerical work and to find empty beds.for the same level of care, and far less effective DAVID HOWE(2) Overtime pay equal to daytime rates.prevention than in the United Kingdom.Department of Obstetrics and Gynaecology, (3) A half day off work after a busy night on call.General practice in Britain is, with all of its Princess Anne Hospital, The government's failure to implement these faults, a model of efficient, personalised, accessible Suthampton S09 4HA demands boldly and swiftly indicates a brutality care compared with what is available in other IButSTringnobercs M71930146(7
The influence of atopic constitution, the severity and exacerbation of the disease on the serum eosinophil cationic protein (ECP) concentration in patients with bronchial asthma
Authors: S. Kovacevic, M. Bogic, A. Peric‐Popadic, Z. Jovicic, S. Raskovic, Lj. Stefanovic
Journal: Allergy (2003)
Six-month outcome in acute kidney injury requiring renal replacement therapy in the ICU: a multicentre prospective study
Authors: B. Delannoy, B. Floccard, F. Thiolliere, M. Kaaki, M. Badet, S. Rosselli, C. E. Ber, A. Saez, G. Flandreau, Claude Guérin
Journal: Intensive Care Medicine (2009)
Curcumin, a constituent of curry, suppresses IgE-mediated allergic response and mast cell activation at the level of Syk
Authors: Jun Ho Lee, Jie Wan Kim, Na Young Ko, Se Hwan Mun, Erk Her, Bo Kyung Kim, Jeung Whan Han, Hoi Young Lee, Michael A. Beaven, Young Mi Kim, Wahn Soo Choi
Journal: Journal of Allergy and Clinical Immunology (2008)
Digoxin-Prescribing
Authors: Michael Weintraub
Journal: JAMA (1979)

We examined digoxin-prescribing in 47,000 prescriptions written predominantly by physicians in a large family medicine practice. Two hundred fifty-four patients received 511 digoxin prescriptions. Dose adjustments for age (16% decrease in patients older than 64 years), for renal disease (33% decrease), and for atrial fibrillation (39% increase) followed good prescribing practices. Appropriately lower loading doses were used for digitalization. However, despite continuing concern over the bioavailability of generic digoxin tablets, less than 40% of digoxin prescriptions in this study were written for the innovator's brand-name product (Lanoxin).