tbuckley/cabot-search huggingface dataset:
Compromises and Controversies — Moving Forward on Reform
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2009)

Accelerating progress toward the Democrats' goal of enacting health care reform legislation, House Speaker Nancy Pelosi (D-CA) unveiled a bill on October 29 that would establish a mandate for most legal U.S. residents to obtain health insurance. The bill would extend coverage to some 36 million people, and according to the Congressional Budget Office (CBO),1 its net costs ($894 billion over 10 years) would be fully paid for — largely through an income-tax surcharge on high-income persons and a reduction in the growth of Medicare's payment rates for most services, except those provided by physicians. Meanwhile, Senate Majority Leader Harry . . .
Abstract A58: Epigenetic silencing of neurotensin receptor type 1 (NTSR1) in colorectal tumor
Authors: Hiromu Suzuki, Eiichiro Yamamoto, Reo Maruyama, Hiro-o Yamano, Masanori Nojima, Akihiro Tsuyada, Takeshi Niinuma, Akiko Sato, Kai Masahiro
Journal: Cancer Research (2013)

Abstract Purpose: Aberrant DNA methylation plays important roles in the development of colorectal cancer (CRC), but its involvement in the flat-type colorectal tumors is poorly understood. In the current study, we aimed to understand the molecular basis of laterally spreading tumors (LSTs) which extend laterally and circumferentially rather than vertically along the colonic wall. Methods: Methylation was examined using Methylated CpG island amplification-microarray (MCAM) and bisulfite-pyrosequencing in colorectal tumors (n=214). Expression of NTSR1 was tested using TaqMan RT-PCR. Colony formation, MTT, Matrigel invasion assays and cDNA microarray were performed to analyze the functional of NTSR1. Results: MCAM analysis in LSTs identified a number of frequently methylated genes including neurotensin receptor type 1 (NTSR1), a known oncogene in CRC. LSTs showed elevated NTSR1 methylation levels than other types of colorectal tumors (p &amp;lt; 0.001). Ectopic expression of NTSR1 promoted colon cancer cell growth and invasiveness. Conversely, siRNA-induced knockdown of NTSR1 in CRC cells suppressed proliferation and invasiveness. Conclusions: Our results suggest that methylation of NTSR1 is associated with invasive behavior and lateral growth of colorectal tumors. Methylation of NTSR1 may be a useful marker to predict the growth pattern of colorectal tumors. Citation Format: Hiromu Suzuki, Eiichiro Yamamoto, Reo Maruyama, Hiro-o Yamano, Masanori Nojima, Akihiro Tsuyada, Takeshi Niinuma, Akiko Sato, Kai Masahiro. Epigenetic silencing of neurotensin receptor type 1 (NTSR1) in colorectal tumor. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A58.
Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer
Authors: Gabriela Bindea, Bernhard Mlecnik, Marie Tosolini, Amos Kirilovsky, Maximilian Waldner, Anna C. Obenauf, Helen Angell, Tessa Fredriksen, Lucie Lafontaine, Anne Berger, Patrick Bruneval, Wolf Herman Fridman, Christoph Becker, Franck Pagès, Michael R. Speicher, Zlatko Trajanoski, Jérôme Galon
Journal: Immunity (2013)
Case 38-1969
Authors: Homayoun Kazemi, Irwin K. Kline
Journal: New England Journal of Medicine (1969)

Presentation of CaseAn eighteen-year-old man was admitted to the hospital because of cough and dyspnea.He had been well until fifteen days previously, when there was the onset of a cough accompanied by pain in the anterior and posterior portions of the chest. Five days later an x-ray film of the chest was said to show bilateral lower-lobe pneumonia; the heart was normal. On admission to another hospital the temperature was 99.6°F, the pulse 120, and the blood pressure 100 systolic, 72 diastolic. The hematocrit was 38 per cent, and the white-cell count 10,000, with 82 per cent neutrophils . . .
Human Insulin Analog Insulin Aspart Does Not Cause Insulin Allergy
Authors: Hisafumi Yasuda, Masao Nagata, Hiroaki Moriyama, Kazuhiro Fujihira, Reiko Kotani, Katsumi Yamada, Hiroo Ueda, Koichi Yokono
Journal: Diabetes Care (2001)

Human insulin is beneficial for most diabetic patients for whom insulin therapy is indispensable. However, some patients suffer from insulin allergy. Insulin allergies are immunologic reactions to exogenous insulin, which cause local or systemic symptoms. Here we report that insulin aspart, a human insulin analog, alleviated local and generalized insulin allergy in the absence of anti-allergic agents in a Japanese patient.

A 59-year-old woman (60 kg body wt, BMI 24.4 kg/m2) with bronchial asthma was admitted to our hospital in December 2000 for the treatment of uncontrolled diabetes. She was first diagnosed as having type 2 diabetes in 1996 and started on treatment with oral hypoglycemic agents. However, hyperglycemia was difficult to control, and treatment with human …
DETERMINATION OF DELAY REQUIRED TO PERMIT SPECT THALLIUM MYOCARDIAL PERFUSION IMAGING AFTER Nal-131 THYROID ABLATION.
Authors: C. J. Branstetter, T. D. Payne, J. J. Pippin, J. J. Nemec, A. D. Ross, S. M. Devers, C. M. Carr, S. J. Durham
Journal: Clinical Nuclear Medicine (1997)

Branstetter, C. J.; Payne, T. D.; Pippin, J. J.; Nemec, J. J.; Ross, A. D.; Devers, S. M.; Carr, C. M.; Durham, S. J. Author Information
Abstract 2240: Pre-clinical potency of INK128, a highly potent TORC1/2 kinase inhibitor in the <i>HER2</i> amplified breast cancer model
Authors: Pradip KR. De, Yuliang Sun, Hui Wu, Christian Rommel, Liu Yi, Nandini Dey, Brian Leyland-Jones
Journal: Cancer Research (2012)

Abstract Background: The PI3K-AKT-mTOR pathway is commonly activated in breast cancers due to the amplification of receptor tyrosine kinase (HER2), the mutation of PIK3CA or the loss of expression/function of PTEN. About 20% of HER2+ breast cancer patients have PIK3CA mutation, which has resulted in a trend toward shorter progression-free survival with trastuzumab-based therapy. Resistance (intrinsic or acquired) to trastuzumab is a significant clinical challenge, partly due to the overriding activation of PI3K-AKT-mTOR pathway. The PI3K pathway activation leads to stimulation of the key growth and proliferation regulatory kinase, mTOR which can be blocked by allosteric inhibitors (rapalogous) or by ATP-comptetive mTOR kinase inhibitor (TORC1/2). Purpose: We investigated the effects of INK128; a potent and selective TORC1/2 kinase inhibitor alone or in conjunction with trastuzumab in HER2 amplified breast tumor cell lines. We also sought to identify the molecular response determinants of mTOR kinase inhibitor predicting potent activity in HER2+/trastuzumab-resistant cell lines. Experimental Design: Here, we used the HER2 amplified trastuzumab-sensitive breast tumor cell line (BT474), the trastuzumab-resistant breast tumor cell line (BT474HR) and HER2 amplified/PIK3CA mutated breast tumor cell lines (HCC1954, UACC893). Results: We demonstrate that 1) HER2+ cells are sensitive to INK128 (IC50 ∼40nM), 2) INK128 is also effective in trastuzumab-resistant and PIK3CA mutaed/HER2+ breast tumor cells (IC50 ∼20 and 20-30nM respectively), 3) INK128 is mechanistically distinct from rapalogous by a more potent and comprehensive inhibition of PI3K-AKT-mTOR signaling network: a) avoids S6K inhibition-mediated feedback activation of PI3K-AKT and b) abrogates 4EBP1 phosphorylation; 4) ligand-induced HIF1α accumulation is inhibited by prior treatment of INK128, and 5) the combination of trastuzumab plus INK128 more effectively blocked PI3K-AKT-mTOR signaling and HIF1α accumulation both in parental and trastuzumab-resistant cells. Conclusion: Our results suggest that i) therapeutic targeting of PI3K-AKT-mTOR signaling should be effective in abrogating resistance to trastuzumab therapy in HER2+ breast cancer, ii) combination of trastuzumab and INK128 is a promising treatment approach for HER2 overexpressed as well as trastuzumab-resistant breast cancer patients and iii) dual TORC1/2 inhibitor also mitigates the feedback activation of AKT caused by selective inhibition of mTORC1, and because of this, INK128 may yield greater therapeutic benefit in breast cancer patients. 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 2240. doi:1538-7445.AM2012-2240
Effective glomerular filtration pressure and single nephron filtration rate during hydropenia, elevated ureteral pressure, and acute volume expansion with isotonic saline
Authors: Vittorio E. Andreucci, Jaime Herrera-Acosta, Floyd C. Rector, Donald W. Seldin
Journal: Journal of Clinical Investigation (1971)

Free-flow and stop-flow intratubular pressures were measured in rats with an improved Gertz technique using Landis micropipets or a Kulite microtransducer. In hydropenia, average single nephron glomerular filtration rate was 29.3 nl/min, glomerular hydrostatic pressure (stop-flow pressure + plasma colloid osmotic pressure) was 70 cm H(2)O and mean glomerular effective filtration pressure was 12.7-14.3 cm H(2)O, approaching zero at the efferent end of the glomerulus. Thus, the glomerulus is extremely permeable, having a filtration coefficient four to five times greater than previously estimated. Mean effective filtration pressure and single nephron glomerular filtartion rate fell with elevated ureteral pressure and rose with volume expansion, more or less proportionately. Changes in effective filtration pressure were due primarily to increased intratubular pressure in ureteral obstruction and to reduced plasma colloid osmotic pressure in volume expansion; glomerular hydrostatic pressure remained constant in both conditions and thus played no role in regulation of filtration rate.
Comparative allergenicity studies of native and recombinant <i>Blomia tropicalis</i> Paramyosin (Blo t 11)
Authors: J. D. A. Ramos, A. S. M. Teo, K. L. Ou, L. C. Tsai, B. W. Lee, N. Cheong, K. Y. Chua
Journal: Allergy (2003)

Background: The complementary DNA (cDNA) encoding for Blo t 11, a 102 kD allergen from Blomia tropicalis (Bt) was isolated, expressed and characterized previously. This study aimed to isolate the native Blo t 11 allergen and compare its allergenicity with the recombinant forms. Methods: Native Blo t 11 (nBlo t 11) was isolated from crude Bt extract by immuno‐affinity chromatography, analyzed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and Western blot, and verified by MALDI‐TOF MS. Recombinant full‐length Blo t 11 (rFL‐Blo t 11) and its immunodominant peptide (fD) were expressed as glutathione S‐transferase (GST)‐fusion proteins in Escherichia coli . Immunoglobulin E (IgE) reactivity of the Blo t 11 allergens were determined by enzyme‐linked immunosorbent assay (ELISA) and skin prick test. The inhibition capacity of the nBlo t 11 against fD and vice versa was determined by absorption studies. Results: Affinity purified nBlo t 11 was susceptible to degradation with the major degraded product resolved at ∼66 kD. The nBlo t 11 was confirmed by immunoblot analysis and MALDI‐TOF MS that generated 13 peptides with complete identity to the deduced amino acid sequence of Blo t 11. Comparative in vitro and in vivo allergenicity tests and the cross inhibition studies between the native and recombinant Blo t 11 showed that recombinant fD, but not the rFL‐Blo t 11, has comparable IgE reactivity with the native counterpart. Conclusions: This comparative study confirmed that the recombinant peptide fD contains the main immunodominant region of Blo t 11. This recombinant peptide, instead of the full‐length protein, is a good candidate for diagnostic and therapeutics development for mite allergy.
Experiments on People
Authors: Irvine H. Page
Journal: JAMA (1975)

THE CURRENT literature on human experimentation is so filled with claims, counterclaims, and confusion, I would seriously doubt that most physicians or researchers are able either to understand the problems or to follow the supposedly clarifying guidelines. These range from the complexities of "Protection of Human Subjects," by the Department of Health, Education and Welfare, to the simple declarations of the American Medical Association and Helsinki. Not that these guidelines are wrong, but to interpret and apply them properly is a formidable task and not made easier by the professional ethicists and moralists. It sounds somewhat absurd to say that what is needed is a large dose of<i>common sense!</i> As things now stand, many investigators are seeking connections outside the United States where practical judgment still has a voice. Others are going about their research ignoring the threatened strictures, and a few have quit clinical research. In short, the
Stiffness Indexes β of the Common Carotid and Femoral Arteries Are Associated With Insulin Resistance in NIDDM
Authors: Masanori Emoto, Yoshiki Nishizawa, Takahiko Kawagishi, Kiyoshi Maekawa, Yoshikazu Hiura, Hiroyuki Kanda, Kyoko Izumotani, Tetsuo Shoji, Eiji Ishimura, Masaaki Inaba, Yasuhisa Okuno, Hirotoshi Morii
Journal: Diabetes Care (1998)

To investigate the association between arterial wall stiffness indexes beta of the common carotid artery (CCA) and the femoral artery (FA) and insulin resistance in NIDDM subjects in a cross-sectional study.We evaluated the arterial stiffness indexes beta of CCA and FA using an ultrasonic phase-locked echo-tracking system in 60 NIDDM subjects attending the diabetes center in Osaka City University Hospital, compared with 120 age- and sex-matched control subjects. Insulin sensitivity indexes were evaluated using a euglycemic-hyperinsulinemic clamp.Stiffness indexes beta of both CCA and FA were significantly higher in NIDDM subjects than in control subjects (CCA 18.1 +/- 0.9 vs. 11.7 +/- 0.3, respectively, P < 0.001; FA 35.7 +/- 2.3 vs. 23.7 +/- 0.8, respectively, P < 0.001). The mean insulin sensitivity index in NIDDM subjects was 4.69 +/- 0.29 mg.kg-1.min-1.mU-1.l. The stiffness indexes beta of both CCA and FA were inversely correlated with insulin sensitivity indexes (CCA r = -0.393, P = 0.002; FA r = -0.329, P = 0.010), as well as with age, duration of diabetes, and mean blood pressure. In stepwise multiple regression analyses, insulin sensitivity index and duration of diabetes were identified as significant independent variables for stiffness indexes beta in both CCA and FA (CCA R2 = 0.249, P = 0.0003; FA R2 = 0.336, P < 0.001).Arterial stiffness indexes beta of CCA and FA were associated with insulin resistance in NIDDM subjects.
Revelation and the single lens.
Authors: B J Ford
Journal: BMJ (1982)

Perhaps the most misunderstood instrument in the history of medicine is the simple microscope.It is seen as an unsightly plaything, a single bead of glass or semi-precious mineral, generating hazy and multi-coloured images that were blurred and distorted.'I have reconstructed many of the pioneer experiments using microscopes from the period covering the late seventeenth century to the early nineteenth, and find that in practice the performance of these single-lensed instruments far exceeds such preconceptions.The images that can be obtained compare favourably with what we would expect to see today. Antony van LeeuwenhoekThe simplest of these microscopes must be the type made by the great pioneer of microscopy, Antony van Leeuwenhoek.This year saw the 350th anniversary of his birth.Leeuwenhoek, who did not begin his half-century of devotion to the science of microscopy until he was nearly 40, made some 4-500 little micro- scopes by rivetting together rectangular plates of metal (often brass or silver) which he had perforated with an aperture in which the lens was "sandwiched".The specimen was usually held on a small metal pointer in place of a stage, and it could be moved into position and then focused by two screws set at right-angles to each other.The whole instrument was around 50 mm in length, and observations were made by holding the microscope close to the eye and illuminating it with a restricted cone of light.This would be a candle or a lamp-flame, or for daylight observations the light from a distant window.Leeuwenhoek understood the need to restrict the aperture of his iUuminant in order to obtain a clearly defined image. . . . ~~~õ ' r % H ' ~~~~~~~L SUnstained smear of author's erythrocytes imaged with Leeuwenhoek microscope in fig 1 .View compares favourably with a modem microscope of medium power, and bacteria can be satisfactorily resolved by this lens, which dates from around 1700.Photograph of original Leeuwenhoek microscope at the University of Utrecht and diagram showing its construction.Specimen was glued or impaled on point adjacent to single lens.Note positioning screws and small lens aperture immediately behind pointer.The entire assembly is less than 50 mm long.
Diabetic Angiopathy and L-xylulose
Authors: John R. Shaw
Journal: JAMA (1966)

A POSSIBLE MECHANISM for the origin of diabetic angiopathy through insulin deficiency has been postulated by Spiro. 1 He suggests that glucose utilization may be diverted into insulin-independent pathways with resulting formation of excess glycoprotein. Winegrad and Burden 2 demonstrated a persistently increased serum level of L-xylulose, a nonphosphorylated intermediate in the glucuronic acid pathway, in diabetic patients. This increase had no apparent relation to blood glucose levels. In addition, they demonstrated that insulin produced a consistently prompt fall in the serum L-xylulose levels in diabetic patients. This report describes a patient with minimal impairment of glucose tolerance, but with severe diabetic angiopathy and a high serum level of L-xylulose.  Report of a Case  A 52-year-old Spanish man was tested for diabetes five years ago because of an ischemic ulcer on the left great toe. His glucose tolerance curve showed a fasting glucose level of 93 mg/100 ml, at 30
Gene Regulatory Networks in the Genomics Era
Authors: Matthew Loose, Roger Patient, Xiangdong Fang, Hongxing Lei
Journal: Genomics Proteomics & Bioinformatics (2013)

The precise regulation of gene expression is critical to the normal development and biological function of all organisms. Dysregulation of gene expression during early development can result in a spectrum of failures ranging from minor defects to the termination of development. In adult life, dysregulation can lead to the uncontrolled cell proliferation of cancer or programmed cell death leading to neurodegenerative diseases. The regulation of gene expression is controlled by multiple systems with more being discovered. The immediate regulators are transcription factors which bind to specific sequences in the promoter or enhancer regions of individual genes. The activity of transcription factors can be regulated by the presence of other transcription factors and cofactors, methylation status of the promoter or enhancer region, accessibility of the DNA due to the local compactness of the chromatin and various modifications of the histone tails. Transcribed mRNAs are then subject to degradation before being translated into protein products, during which microRNAs play a major role [1]. In this special issue, we present recent advances in the elucidation of gene regulatory networks (GRNs). After the completion of the human genome project, people realized that even excluding the repetitive sequences, protein coding regions are only a small portion of the whole genome. To explore the functional roles of the ‘‘junk’’ regions, the National Institutes of Health (NIH) started the encyclopedia
Oncostatin M Renders Epithelial Cell Adhesion Molecule–Positive Liver Cancer Stem Cells Sensitive to 5-Fluorouracil by Inducing Hepatocytic Differentiation
Authors: Taro Yamashita, Masao Honda, Kouki Nio, Yasunari Nakamoto, Tatsuya Yamashita, Hiroyuki Takamura, Takashi Tani, Yoh Zen, Shuichi Kaneko
Journal: Cancer Research (2010)

Abstract Recent evidence suggests that a certain type of hepatocellular carcinoma (HCC) is hierarchically organized by a subset of cells with stem cell features (cancer stem cells; CSC). Although normal stem cells and CSCs are considered to share similar self-renewal programs, it remains unclear whether differentiation programs are also maintained in CSCs and effectively used for tumor eradication. In this study, we investigated the effect of oncostatin M (OSM), an interleukin 6–related cytokine known to induce the differentiation of hepatoblasts into hepatocytes, on liver CSCs. OSM receptor expression was detected in the majority of epithelial cell adhesion molecule–positive (EpCAM+) HCC with stem/progenitor cell features. OSM treatment resulted in the induction of hepatocytic differentiation of EpCAM+ HCC cells by inducing signal transducer and activator of transcription 3 activation, as determined by a decrease in stemness-related gene expression, a decrease in EpCAM, α-fetoprotein and cytokeratin 19 protein expressions, and an increase in albumin protein expression. OSM-treated EpCAM+ HCC cells showed enhanced cell proliferation with expansion of the EpCAM-negative non-CSC population. Noticeably, combination of OSM treatment with the chemotherapeutic agent 5-fluorouracil (5-FU), which eradicates EpCAM-negative non-CSCs, dramatically increased the number of apoptotic cells in vitro and suppressed tumor growth in vivo compared with either saline control, OSM, or 5-FU treatment alone. Taken together, our data suggest that OSM could be effectively used for the differentiation and active cell division of dormant EpCAM+ liver CSCs, and the combination of OSM and conventional chemotherapy with 5-FU efficiently eliminates HCC by targeting both CSCs and non-CSCs. Cancer Res; 70(11); 4687–97. ©2010 AACR.
Decentralised health care in Canada
Authors: P. Armstrong, H. Armstrong
Journal: BMJ (1999)

Editorials by Leys and Diderichsen 

An indicator of the size of Canada is that St John's, Newfoundland, is equidistant from Moscow and Dawson City, Yukon. Yet Canada has a population of just over 30 million. Its 10 provinces vary in population from tiny Prince Edward Island with under 140 000 inhabitants to Ontario with well over 11 million. Its three territories together have barely 100 000 residents spread over 3.9 million square kilometres of land.



Since Canada became a nation in 1867, health care has been primarily the responsibility of the provinces



It is no surprise, then, that since its inception the Canadian public healthcare system has been decentralised. Since Canada became a nation in 1867, health care has been primarily a responsibility of the provinces. They have strongly defended their rights, and have often been supported by private insurers and providers in their resistance to a national health system. Yet the 1937 Royal Commission on Dominion-Provincial Relations emphasised the chaotic financial results on business if some provinces, acting independently on health insurance, levied taxes on employers that placed them in a less competitive position with respect to business in provinces that did not.1 Thus, when a public healthcare system became a top priority after the second world war, planners sought to balance local control with the need for some degree of uniformity throughout Canada, and therefore in the collection of tax contributions by the federal government.

The federal government, unable to achieve federal-provincial consensus, used its spending power to bring provinces into a national plan. The strategy was simple. Making an offer no province could resist, the federal government promised to pay half the costs of hospitals and, later, of doctors' services, as long as the provinces conformed to some basic principles. These two initiatives were later brought …