tbuckley/cabot-search huggingface dataset:
Abstract B39: IGF-IR regulation of osteoclastogenesis in neuroblastoma bone metastasis
Authors: Chris A. Rivera-Pintado, Yufei Shan, Cynthia M. van Golen
Journal: Cancer Research (2014)

Abstract Neuroblastoma is a tumor that is responsible for 15% of cancer deaths in children and has a mortality rate greater than 90% percent upon metastasis to bone. Due to the high mortality rate and lack of effective treatment options, our laboratory is investigating potential new therapeutic targets in neuroblastoma bone metastases. Since, insulin-like growth factor I (IGF-I) production in the bone promotes neuroblastoma growth and survival, our hypothesis is that inhibiting IGF-I receptor (IGF-IR) will prevent metastasis of this tumor to bone. Furthermore, neuroblastoma with increased IGF-IR expression induces osteoclasts to differentiate, with the percentage of differentiated osteoclasts in vitro increasing to 30% in the presence of conditioned medium from high IGF-IR expressing cells. The addition of a monoclonal, neutralizing antibody to the IGF-IR decreases the percentage of mature osteoclasts formed by over 50%. We are testing the hypothesis that IGF-IR activation in neuroblastoma alters the levels of RANK, RANKL and OPG, proteins involved in osteoclast differentiation. This alteration in RANK, RANKL, and OPG may cause osteoclast differentiation and osteolysis. Neuroblastoma cells with high IGF-IR protein levels express low levels of the decoy receptor OPG, while some lines also express high levels of RANKL. Therefore, we are currently testing the effect of IGF-IR inhibition on RANKL and OPG levels and subsequent effect on osteolysis. Citation Format: Chris A. Rivera-Pintado, Yufei Shan, Cynthia M. van Golen. IGF-IR regulation of osteoclastogenesis in neuroblastoma bone metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B39.
Women with early breast cancer to be tested for trastuzumab treatment
Authors: Susan Mayor
Journal: BMJ (2005)

All women in England with early stage breast cancer are to be tested to see if they could benefit from trastuzumab (Herceptin), and approval for use of the drug by the NHS will be fast tracked once it has been licensed. The government announced these measures last week after a campaign by women demanding prompt access to this treatment.

Health Secretary Patricia Hewitt announced that all women diagnosed with early stage breast cancer would be tested for suitability for treatment with trastuzumab. The drug is a monoclonal antibody that binds to the HER2 receptor, a cell surface protein that can be tested for and which is overexpressed in about a fifth of breast cancers. The drug is currently licensed for use only in women with advanced breast cancer who test positive for HER2, but studies reported to the American Society of Clinical Oncology in May this year claimed that it reduced the risk of recurrence in early breast cancer.

In response to Ms Hewitt's announcement, the national cancer director, Mike …
Association Between Serum Total Bilirubin Levels and the Morphology of Corneal Nerve Fibers in Japanese Patients With Uncontrolled Type 2 Diabetes
Authors: Fukashi Ishibashi, Asami Kawasaki, Rie Kojima, Miki Taniguchi, Aiko Kosaka, Harumi Uetake
Journal: Diabetes Care (2014)

Oxidative stress (OS) plays a key role in the development of diabetes complications. Bilirubin is a potent antioxidant, and serum total bilirubin (TB) levels in the low-normal range are associated with diabetic retinopathy (1) and nephropathy (2) and are predictive of lower-limb amputation (3). However, the relationship between serum TB and diabetic neuropathy has not been reported. Due to constant exposure to OS (sunlight and ambient air) and poor antioxidant activity due to its avascularity, the cornea is vulnerable to OS (4). Diabetes increases the OS burden on the cornea. Corneal nerve fibers (CNFs) are composed of unmyelinated C-fibers, which are the first nerve fibers to undergo damage and subsequent repair. We examined the association between serum TB and CNF morphology in patients with uncontrolled type 2 diabetes (T2D).

Cross-sectional data were collected from 384 …
Worldwide water crisis is a “silent emergency,” UN agency says
Authors: Peter Moszynski
Journal: BMJ (2006)

Unclean water is an “immeasurably greater threat to human security than violent conflict” across the developing world, says the latest annual report from the United Nations Development Programme. 

The report says, “‘Not having access to clean water' is a euphemism for profound deprivation. It means that people walk more than one kilometre to the nearest source of clean water for drinking, that they collect water from drains, ditches or streams that might be infected with pathogens and bacteria that can cause severe illness and death.” 

Each year 1.8 million children die from diarrhoea that could be prevented; 443 million school …
Diabetes in East Pakistan
Authors: Md. Ibrahim
Journal: BMJ (1962)

Since the advent of oral hypoglycaemic agents in diabetic therapy newer vistas have been opened up in research on diabetes mellitus in regard not only to its management but also to its aetiology and pathogenesis.Peculiarities in the character of diabetes in tropical regions were noted in the early part of this ccntury, and various authors discussed their observations in a symposium in the Section of Tropical Medicine of the British Medical Association's Annual Meeting in 1907 (British Medical Journal, 1907).The most significant of these peculiarities were rarity of juvenile diabetes, infrequency of ketosis, and diabetic coma.During the last decade clinical studies by DeZoysa (1951), Hugh-Jones (1955), and Cosnett (1959) clearly showed that diabetes in the tropics differs widely from that in temperate climates.Different authorities have described various types of diabetes, such as type 1 and type 2 (Lawrence, 1951) and type J (Hugh-Jones, 1955).In a stimulating leading article in the British Medical Journal (1959) the types of diabetes were discussed and the need for further studies in the tropics was stressed, concluding with the remark of Sir Harold Himsworth that " a primary deficiency of insulin is only one, and then not the commonest, cause of the diabetic syndrome."The present paper records the result of a study of 894 cases of diabetes in East Pakistan.As there was no special clinic in the country to deal with these cases, and as illiteracy, poverty, and superstition often made dietary control and insulin treatment difficult or uncertain, a Diabetic Association was organized in the early part of 1956 and arrangements were made to contact as many diabetics as possible by newspapers, seminars, and conferences.A research section was started under the auspices of the Pakistan Medical Research Council in the Medical Research Centre at Dacca, where all the examinations, including repeated glucose-tolerance tests and other relevant biochemical procedures, were done free of cost.Method anid Materials.-Theperiod covers the 28 months from August, 1957, to December, 1959.All the 894 patients were studied in the Medical Research Centre and arrangements were made to call them at regular intervals, fortnightly or monthly, for assessment and glucose-tolerance tests.The procedure of examinations has been fully described (Ibrahim, 1959).
Training for overseas doctors: Trainees need designated teaching posts
Authors: D P Cartwright
Journal: BMJ (1993)

and about 65 trainees.No posts are set aside or reserved either for British doctors or for those on the scheme.I endorse the final recommendation-that doctors should not come to the United Kingdom unless they have a specific understanding concerning their appointment-but this is a matter for the organisers of the Overseas Doctors Training Scheme in London and Edinburgh.
Magnetic Resonance Pancreatography
Authors: M. Barish, J. Soto, J. Ferrucci
Journal: Endoscopy (1997)

Magnetic resonance cholangiopancreatography (MRCP) uses magnetic resonance (MR) pulse sequences in which static fluid appears bright against a low signal or dark background. When these MR images are subjected to postprocessing techniques, they produce images that resemble the pancreatograms obtained using endoscopic retrograde cholangiopancreatography (ERCP). The MRCP examination is easily performed, is noninvasive, requires no contrast injection, and has no known complications. The place of MRCP in the evaluation of disorders of the pancreas is not yet fully established, but several well-defined roles have already emerged. These include the evaluation of the pancreatic duct after failed or incomplete ERCP, and the evaluation of complete pancreatic duct obstruction. The technical aspects required for MRCP of the pancreatic duct, and the established and emerging roles for MRCP in the pancreatic duct, are described here.
THE METABOLISM OF AMINO ACIDS AND CASEIN DIGEST IN PHLORHIZINIZED DOGS
Authors: W. B. Hawkins, F. W. McKee, G. M. B. Hawley, A. J. Kummer
Journal: The Journal of Experimental Medicine (1947)

When solutions of sugar-forming amino acids are given parenterally or orally to phlorhizinized dogs, extra sugar and nitrogen are excreted in the urine. The route of administration does not influence the way in which the amino acids are metabolized. 89 percent of the expected sugar was recovered when the acids were fed and 81 per cent when the acids were administered parenterally. Casein digests are metabolized like the amino acids with extra sugar and nitrogen excreted in the urine. When casein digest is given orally there is an average conversion into sugar of 53 per cent, as compared with 56 per cent intravenously. Solutions of amino acids or casein digests are readily available sources to the body of nitrogen and carbohydrate.
FACTORS AFFECTING FREQUENCY OF PATIENT USE OF INTERNET-BASED TELEMEDICINE SYSTEM TO MANAGE CHRONIC CARDIOVASCULAR DISEASE RISK CONDITIONS
Authors: Priya Rao Kothapalli, Alfred Bove, William Santamore, Carol Homko, Abul Kashem, Timothy McConnell, Gail Shirk, Francis Menapace
Journal: Journal of the American College of Cardiology (2012)
Does Academic Medicine Matter?
Authors: Jocalyn Clark, Peter Tugwell
Journal: PLoS Medicine (2006)

Academic medicine occupies a spot in that rarefied world in which one doesn't have to do much to justify one's existence. The best health care, the best research, the brightest minds on the planet circulate within academic medicine, together conspiring for the benefit of patients and practitioners.

Correct? Perhaps not, as growing concern about a decline in the state of academic medicine around the world threatens this taken-for-granted position [1–6]. In the past few years more and more critics have questioned the role and contribution of academic medicine—to society, to health-care systems, and to patients [7]. Who is academic medicine for? Why does it matter? What added value does it bring to disease prevention, health promotion, and the practice of health care? In order to engage our stakeholders—which include policymakers and the public—we need to demonstrate the benefits of academic medicine.

Revitalising academic medicine matters because health costs and expectations are rising alongside growing concerns that academic medicine is failing to produce sufficient gains for patients and funders. As others have argued, it is time for academic medicine to step up to the plate—to take leadership in redressing the gaps between bench and bedside medicine [8] and between the rich and the poor [9,10]. Taking leadership involves better preparation for future health-care demands in terms of attracting suitable and sufficient human resources, and aligning priorities with global health needs.

That said, however, the case for why and how academic medicine ought to lead us forward must be evidence-based. At a time when there is increasing demand for academic medicine to be more accountable, we find that the evidence base for its effectiveness is rather slim. Fortunately there is mounting interest in evaluating the impact of academic medicine across the traditional triad of medical research, education, and clinical care.

For example, in May of this year, the Academy of Medical Sciences released its report on the benefits of medical research to society (http://www.acmedsci.ac.uk/images/project/Medicalr.pdf). The Association of American Medical Colleges (http://www.aamc.org) has led work on improving the quality of medical education for the next generation of doctors and other health practitioners. And in a new systematic review in PLoS Medicine, John Ioannidis and colleagues examine the benefits of academic health care in terms of clinical outcomes [11].
Selenium: A Case for Its Essentiality in Man
Authors: Vernon R. Young
Journal: New England Journal of Medicine (1981)

About 45 essential nutrients are needed for health maintenance, and among them are some 15 minerals or metals.1 Many of these minerals are required in small amounts in normal diets, but their specific role in human health is still a matter for exploration. A trace element of current interest is selenium, whose role in the nutrition of various animal species is now well established. A dietary deficiency of selenium causes muscular dystrophy in ruminants (sheep and cattle), pancreatic degeneration and exudative diathesis in poultry, and liver necrosis in rats.2 Indeed, recognition of the importance of selenium in poultry nutrition has . . .
Abstract 1914: Potent anticancer activity against both BRAF-mutant and BRAF wild-type melanoma cell lines using a novel CRM1 nuclear export inhibitor
Authors: Roberto A. Salas Fragomeni, Hye-Won Chung, Sharon Shacham, Michael Kauffman, James C. Cusack
Journal: Cancer Research (2012)

Abstract INTRODUCTION: BRAF and NRAS oncogenic mutations occur in over half of all human melanomas. BRAF-mutant tumors are highly sensitive to small molecule inhibitors directed against the oncogenic BRAF protein. However, in tumors that lack the specific mutation, patients have few effective therapeutic options. To address the need for new therapies for patients with BRAF-wild-type (wt) melanoma, we hypothesized that the inhibition of the major nuclear export receptor CRM1 would result in nuclear accumulation of nuclear proteins, increase apoptosis and induce cell cycle arrest independent of BRAF mutational status. To test our hypothesis, we examined the effects of a novel CRM1 inhibitor on melanoma cell lines with various BRAF and NRAS mutational backgrounds. METHODS: We used human malignant melanoma cell lines with BRAF mutation (Sk-Mel-28, A375, Mel-624, UACC903, MalMe-3M), BRAF-wt (MeWo) and BRAF-wt and NRAS mutation (Hs940T) to assess the effects of CRM1 inhibition, BRAF inhibition (PLX4032) or MEK inhibition (U0126) using both mono- or combination therapy. MTT assays were used to evaluate the effects of treatment on cell proliferation. FACS analysis with annexin/PI staining was performed to assess effects on cell cycle and cell death. The Chou-Talalay method was used to assess synergistic drug combination effects. Treatment effects on cleaved caspase-3, PARP cleavage, P53, and FOXO3 were analyzed by western blot analysis. RESULTS: As mono therapy, CRM1 inhibition led to a significant decrease in cell proliferation, cell cycle arrest and an increase in apoptosis in both BRAF wt and mutant cell lines. The degree of inhibition and cell death achieved by CRM1 inhibition across all melanoma cell lines is comparable to the results achieved by BRAF inhibitor PLX4032 in BRAF mutant cell lines. Furthermore, the combination of CRM1 inhibition and BRAF inhibition results in a strongly synergistic combination against BRAF mutant cell lines with a statistically significant decrease in cell proliferation and increased apoptotic cell death. CONCLUSION: We found that relative to other cancer cell types, both BRAF-mutant and BRAF-wt melanoma cells are exquisitely sensitive to CRM1 inhibition. In addition, CRM1 inhibition significantly enhanced the effect of PLX4032 in BRAF-mutant cell lines, suggesting that the combination of these two drugs may address the emergence of acquired resistance to BRAF monotherapy. Based on these results, CRM1 inhibition warrants further investigation to determine its potential benefit in treating melanoma patients independent of BRAF mutation status. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1914. doi:1538-7445.AM2012-1914
Prediction of sudden death and spontaneous ventricular tachycardia in survivors of complicated myocardial infarction: Value of the response to programmed stimulation using a maximum of three ventricular extrastimuli
Authors: Lawrence E. Waspe, David Seinfeld, Aileen Ferrick, Soo G. Kim, Jeffrey A. Matos, John D. Fisher
Journal: Journal of the American College of Cardiology (1985)
Silica and Pulmonary Lesions
Authors: Robert N. Jones
Journal: JAMA (1981)

<h3>To the Editor.—</h3> The article by John E. Craighead, MD, and N. V. Vallyathan, PhD (1980;244:1939), deserves further comment. It consists of two separate and quite different parts. The first part reports the demonstration of silica in lung tissue of deceased granite workers. Using sophisticated electron microscopic and microanalytic techniques (that the authors have helped to develop and refine), the investigators detected silica particles too small to be seen under polarized light microscopy. These techniques are major advances in the methodology of tissue examination and certainly warrant prominent exposition in<i>JAMA</i>. The second part consists of an attempt to relate the tissue findings to standards for workplace silica exposures. This involves a number of inferences. The first is that the silica found was in fact the cause of the fibrosis seen in the same tissue sections. Only one of the 15 cases showed silicotic nodules; the remaining cases showed localized
HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells
Authors: Carmen Urbich, Lothar Rössig, David Kaluza, Michael Potente, Jes-Niels Boeckel, Andrea Knau, Florian Diehl, Jian-Guo Geng, Wolf-Karsten Hofmann, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Blood (2009)
Basal cell carcinoma, squamous cell carcinoma and melanoma of the skin: analysis of the Singapore Cancer Registry data 1968-97
Authors: D. Koh, H. Wang, J. Lee, K.S. Chia, H.P. Lee, C.L. Goh
Journal: British Journal of Dermatology (2003)

Journal Article Basal cell carcinoma, squamous cell carcinoma and melanoma of the skin: analysis of the Singapore Cancer Registry data 1968–97 Get access D. Koh, D. Koh Department of Community, Occupational and Family Medicine, Faculty of Medicine MD3, National University of Singapore, 16 Medical Drive, Singapore 117597 Prof. David Koh. Tel.: (65)68744988. Fax: (65)67791489. E‐mail: cofkohd@nus.edu.sg Search for other works by this author on: Oxford Academic Google Scholar H. Wang, H. Wang Department of Community, Occupational and Family Medicine, Faculty of Medicine MD3, National University of Singapore, 16 Medical Drive, Singapore 117597 Search for other works by this author on: Oxford Academic Google Scholar J. Lee, J. Lee Department of Community, Occupational and Family Medicine, Faculty of Medicine MD3, National University of Singapore, 16 Medical Drive, Singapore 117597 Search for other works by this author on: Oxford Academic Google Scholar K.S. Chia, K.S. Chia Department of Community, Occupational and Family Medicine, Faculty of Medicine MD3, National University of Singapore, 16 Medical Drive, Singapore 117597Singapore Cancer Registry, National University of Singapore Search for other works by this author on: Oxford Academic Google Scholar H.P. Lee, H.P. Lee Department of Community, Occupational and Family Medicine, Faculty of Medicine MD3, National University of Singapore, 16 Medical Drive, Singapore 117597Singapore Cancer Registry, National University of Singapore Search for other works by this author on: Oxford Academic Google Scholar C.L. Goh C.L. Goh National Skin Centre, Singapore Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 6, 1 June 2003, Pages 1161–1166, https://doi.org/10.1046/j.1365-2133.2003.05223.x Published: 01 June 2003 Article history Accepted: 30 September 2002 Published: 01 June 2003
Correction of Laminin-5 Deficiency in Human Epidermal Stem Cells by Transcriptionally Targeted Lentiviral Vectors
Authors: Francesca Di Nunzio, Giulietta Maruggi, Stefano Ferrari, Enzo Di Iorio, Valentina Poletti, Marta Garcia, Marcela Del Rio, Michele De Luca, Fernando Larcher, Graziella Pellegrini, Fulvio Mavilio
Journal: Molecular Therapy (2008)

Deficiency of the basement membrane component laminin-5 (LAM5) causes junctional epidermolysis bullosa (JEB), a severe and often fatal skin adhesion defect. Autologous transplantation of epidermal stem cells genetically corrected with a Moloney leukemia virus (MLV)-derived retroviral vector reconstitutes LAM5 synthesis, and corrects the adhesion defect in JEB patients. However, MLV-derived vectors have genotoxic characteristics, and are unable to reproduce the physiological, basal layer-restricted expression of LAM5 chains. We have developed an alternative gene transfer strategy based on self-inactivating (SIN) or long terminal repeat (LTR)-modified lentiviral vectors, in which transgene expression is under the control of different combinations of promoter-enhancer elements derived from the keratin-14 (K14) gene. Analysis in human keratinocyte cultures and in fully differentiated skin regenerated onto immunodeficient mice showed that gene expression directed by K14 enhancers is tissue-specific and restricted to the basal layer of the epidermis. Transcriptionally targeted lentiviral vectors efficiently transduced clonogenic stem/progenitor cells derived from a skin biopsy of a JEB patient, restored normal synthesis of LAM5 in cultured keratinocytes, and reconstituted normal adhesion properties in human skin equivalents transplanted onto immunodeficient mice. These vectors are therefore an effective, and potentially more safe, alternative to MLV-based retroviral vectors in gene therapy of JEB.Molecular Therapy (2008) 16 12, 1977-1985 doi:10.1038/mt.2008.204.