tbuckley/cabot-search huggingface dataset:
Target for Glycemic Control
Authors: Louis Monnier, Claude Colette
Journal: Diabetes Care (2009)

It is commonly admitted that the glycemic control of patients with type 2 diabetes proceeds from a complex “alchemy” in which the respective contributions of both fasting and postprandial glucose are still a subject of debate (1). A1C, which remains the gold standard for assessing glucose homeostasis, is an integration of both fasting and postprandial glucose variations over a 3-month period (2). From a mathematical point of view, the theory can be formulated as follows (3): ![Formula][1]   where FPG ( t ) and PPG ( t ) are the time courses of fasting and postprandial glucose, respectively.

As a consequence, the glycemic control of patients with type 2 diabetes can be schematically depicted by the “glucose triad,” whose components are as follows: A1C, fasting, and postprandial glucose levels. At present, and even though the debate remains wide open, it seems that the best assessment of glycemic control is provided by the determination of the three above-mentioned components. Most recommendations that have been published by medical organizations in different countries take into account the three parameters, even though the position statements differ around the world, but also within the same country (4).

### A tool for integrating the different periods of daytime

Whereas many physicians continue to emphasize fasting glucose and A1C to guide management of diabetes, observational studies have indicated that glucose testing at postprandial and postabsorptive time points could play an important role (5,6). For instance, lessons from physiology tell us that humans spend half of their lives in postprandial states (7,8). The postprandial state, with respect to glucose, is defined as a 4-h period that immediately follows ingestion of a meal (7). During this period, dietary carbohydrates are progressively hydrolyzed through several sequential enzymatic actions. Even though the insulin response rapidly reduces the postprandial glucose excursion with a return to baseline levels within <2 h, the overall …

 [1]: /embed/graphic-1.gif
Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study
Authors: Nils Wahlgren, Niaz Ahmed, Antoni Dávalos, Gary A Ford, Martin Grond, Werner Hacke, Michael G Hennerici, Markku Kaste, Sonja Kuelkens, Vincent Larrue, Kennedy R Lees, Risto O Roine, Lauri Soinne, Danilo Toni, Geert Vanhooren
Journal: The Lancet (2007)
Heme oxygenase-1 inhibition of MAP kinases, calcineurin/NFAT signaling, and hypertrophy in cardiac myocytes
Authors: J TONGERS
Journal: Cardiovascular Research (2004)

Heme oxygenases (HO) are the rate-limiting enzymes in heme degradation, catalyzing the breakdown of heme to equimolar quantities of biliverdin (BV), carbon monoxide (CO), and ferrous iron. The inducible HO isoform, HO-1, confers protection against ischemia/reperfusion (I/R)-injury in the heart. We hypothesized that HO-1 and its catalytic by-products constitute an antihypertrophic signaling module in cardiac myocytes.The G protein-coupled receptor (GPCR) agonist endothelin-1 (ET-1) (30 nmol/l) stimulated a robust hypertrophic response in cardiac myocytes isolated from 1- to 3-day-old Sprague-Dawley rats, with increases in cell surface area (planimetry), sarcomere assembly (confocal laser scanning microscopy), and prepro-atrial natriuretic peptide (ANP) mRNA expression. Adenoviral overexpression of HO-1, but not beta-galactosidase, significantly inhibited ET-1 induced cardiac myocyte hypertrophy. The antihypertrophic effects of HO-1 were mimicked by BV (10 micromol/l) and the CO-releasing molecule [Ru(CO)3Cl2]2 (10 micromol/l), strongly suggesting a critical involvement of BV and CO in the antihypertrophic effects of HO-1. Both BV and CO suppressed extracellular signal-regulated kinases (ERK1/ERK2) and p38 mitogen-activated protein kinase (MAPK) activation by ET-1 stimulation. Moreover, BV and CO inhibited the prohypertrophic calcineurin/NFAT pathway. This inhibition occurred upstream from calcineurin because BV and CO inhibited NFAT activation in response to ET-1 stimulation but not in response to adenoviral expression of a constitutively active calcineurin mutant. Upstream-inhibition of the calcineurin/NFAT pathway by CO occurred independent from cGMP and cGMP-dependent protein kinase type I (PKG I).Heme oxygenase-1 and its catalytic by-products, BV and CO, constitute a novel antihypertrophic signaling pathway in cardiac myocytes. Biliverdin and CO inhibition of MAPKs and calcineurin/NFAT signaling provides a mechanistic framework how heme degradation products may promote their antihypertrophic effects.
The Preliminary Report of the Findings of the Aspirin Component of the Ongoing Physicians' Health Study
Authors: F E Young, S L Nightingale, R A Temple
Journal: JAMA (1988)

RECENTLY, physicians, their patients, and the population at large simultaneously became aware that a large study of the effects of aspirin use in healthy men had been stopped because of a dramatic favorable effect of aspirin use on the rate of acute myocardial infarction. A special report<sup>1</sup>that gave the results of the aspirin component of the ongoing Physicians' Health Study appeared in the Jan 28, 1988, issue of the<i>New England Journal of Medicine</i>, accompanied by an editorial<sup>2</sup>and a barrage of publicity in the lay press. The print and electronic media almost immediately carried advertising directed toward the lay public about the use of aspirin to prevent myocardial infarction. (The Food and Drug Administration [FDA] regulates the<i>labeling</i>of over-the-counter drugs and the Federal Trade Commission regulates the<i>advertising</i>of over-the-counter drugs.) Given the preliminary nature of the published report, the lack of extensive critical scientific
Office mini-hysteroscopy
Authors: R Campo, Y Van Belle, L Rombauts, I Brosens, S Gordts
Journal: Human Reproduction Update (1999)

The technique of diagnostic hysteroscopy has not yet been accepted generally as an ambulatory, well-tolerated office procedure. Especially in the infertile patient the standard hysteroscopic procedure is poorly tolerated in an office environment. Our prospective registration of 530 diagnostic office mini-hysteroscopies in infertile patients demonstrates that using an atraumatic insertion technique, watery distention medium and the new generation of mini-hysteroscopic endoscopes, hysteroscopy can be performed in an office set-up without any form of anaesthesia and with a high patient compliance. The significant number of abnormal findings (28.5%), the absence of complications and the low failure rate (2.3%) indicate that diagnostic office mini-hysteroscopy should be a first-line diagnostic procedure. Those results are compared with the registration of 4204 consecutive conventional diagnostic hysteroscopies in a routine gynaecological population performed between 1982 and 1989. We conclude that the mini-hysteroscopic system offers a simple, safe and efficient diagnostic method in the office for the investigation of abnormal uterine bleeding, to evaluate the cervix and uterine cavity in the infertile patient, for screening of endometrial changes in patients under hormone replacement therapy or anti-oestrogens as (adjuvant) treatment and, lastly, it may be very helpful for the interpretation of uncertain findings in other diagnostic techniques such as ultrasound, magnetic resonance imaging, blind biopsy or hysterosalpingography.
SU11652 Inhibits tyrosine kinase activity of FLT3 and growth of MV-4-11 cells
Authors: Yao Guo, Yun Chen, Xuesong Xu, Xueqi Fu, Zhizhuang Joe Zhao
Journal: Journal of Hematology & Oncology (2012)

Abstract Background FLT3-ITD and FLT3-TKD mutations are frequently found in acute myeloid leukemia (AML). This makes tyrosine kinase FLT3 a highly attractive target for therapeutic drug development. However, effective drugs have not yet emerged. This study is intended to identify and to characterize new FLT3 inhibitors. Methods By using the protein substrate GST-FLT3S to analyze kinase activity of recombinant proteins carrying the catalytic domain of wild type and mutant forms of FLT3, we screened a chemical library containing 80 known protein kinase inhibitors. We identified SU11652 as a potent FLT3 inhibitor and further employed FLT3-ITD-positive MV- 4–11 cells to study its effects on cell growth, apoptosis, cell cycles, and cell signaling. Results SU11652 strongly inhibited the activity of wild type, D835Y, and D835H mutant forms of FLT3 with IC 50 values of 1.5, 16, and 32 nM, respectively. It effectively blocked the growth of FLT3-ITD -positive MV-4-11 cells at nanomolar concentrations but exhibited much less effects on several other cells which do not carry mutations of FLT3. SU11652 inhibited growth of MV-4-11 cells by inducing apoptosis, causing cell cycle arrest, and blocking activation of the ERK, Akt, and STAT signaling pathways. Conclusion SU11652 is a potent FLT3 inhibitor which selectively targets FLT3-ITD-positive cells. It should serve as a good candidate for development of therapeutic drugs to treat AML.
Paternalism and the Physician's Conscience
Authors: JULIA E. CONNELLY
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 August 1983Paternalism and the Physician's ConscienceJULIA E. CONNELLY, M.D.JULIA E. CONNELLY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-2-276 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I read Dr. Thomasma's article (1) with skepticism. All models for the doctor-patient relationship are shortsighted as they do not acknowledge systems of relationships beyond that of the physician and the patient. Despite this inherent shortcoming, Thomasma's model contains two characteristics that distinguish it from other such models. Both the strength of his physician conscience model and its greatest limitations exist in these two characteristics. First, his model requires that physicians assess beliefs, attitudes, and emotions they recognize in response to their patients in an effort to determine how these factors influence the health care they provide....Reference1. THOMASMA D. Beyond medical paternalism and patient autonomy: a model of physician conscience for the physician-patient relationship. Ann Intern Med. 1983;98:243-8. LinkGoogle Scholar1. THOMASMA D. Beyond medical paternalism and patient autonomy: a model of physician conscience for the physician-patient relationship. Ann Intern Med. 1983;98:243-8. LinkGoogle Scholar2. HILFIKER D. Allowing the debilitated to die: facing our ethical choices. N Engl J Med. 1983;308:716-9. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The University of Rochester Medical Center Rochester, NY 14642 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1983Volume 99, Issue 2Page: 276-277KeywordsEmotionsHealth care Issue Published: 1 August 1983 PDF downloadLoading ...
Increased in Vivo Amyloid-β42 Production, Exchange, and Loss in Presenilin Mutation Carriers
Authors: Rachel Potter, Bruce W. Patterson, Donald L. Elbert, Vitaliy Ovod, Tom Kasten, Wendy Sigurdson, Kwasi Mawuenyega, Tyler Blazey, Alison Goate, Robert Chott, Kevin E. Yarasheski, David M. Holtzman, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman
Journal: Science Translational Medicine (2013)

Aβ42 kinetics are altered in the central nervous system of patients with autosomal dominant Alzheimer’s disease.
Reciprocal regulation of MicroRNA-99a and insulin-like growth factor I receptor signaling in oral squamous cell carcinoma cells
Authors: Yi-Chen Yen, Shine-Gwo Shiah, Hsiao-Chien Chu, Yuan-Ming Hsu, Jenn-Ren Hsiao, Jang-Yang Chang, Wen-Chun Hung, Chun-Ta Liao, Ann-Joy Cheng, Ya-Ching Lu, Ya-Wen Chen
Journal: Molecular Cancer (2014)

Abstract Background MicroRNAs (miRNAs), small noncoding RNA molecules can function as oncogenes or tumor suppressors in tumorigenesis. Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide with a 5-year survival rate of approximately 50%. Methods The expression of microRNA-99a (miR-99a) in OSCC tissues and cell lines was investigated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. The functions of miR-99a in migration/invasion and lung colonization were determined by transwell and tail vein injection assays, respectively. Specific targets of miR-99a were determined by software prediction, correlation with target protein expression, and luciferase reporter assay. The signaling pathways involved in regulation of miR-99a were investigated using the kinase inhibitors. Results We observed reduced levels of miR-99a, identified as one of the most downregulated miRNA in OSCC and all tested OSCC cell lines compared to normal oral keratinocytes. Ectopic miR-99a expression in OSCC cells markedly reduced migration and invasion in vitro as well as lung colonization in vivo. When evaluating the specific targets of miR-99a, we found that ectopic miR-99a expression downregulates insulin-like growth factor 1 receptor (IGF1R) protein and that the expression of miR-99a correlates negatively with IGF1R protein in OSCC cells. Insertion of the 3′UTR of IGF1R mRNA into the 3′UTR of a reporter gene markedly reduced luciferase activity in OSCC cells expressing miR-99a, suggesting that miR-99a reduces luciferase activity by targeting the 3′UTR of IGF1R mRNA. When evaluating the mechanisms of miR-99a downregulation, we observed the upregulation of miR-99a expression in serum-starved conditions and its suppression in response to insulin-like growth factor (IGF1) stimulation. Inhibitors of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) kinase inhibited IGF1-induced suppression of miR-99a, suggesting the negative regulation of miR-99a expression by IGF1R signaling. Conclusion Overall, results indicate that miR-99a functions as a tumor metastasis suppressor in OSCC cells and mutually regulates IGF1R expression in a reciprocal regulation.
Capsule pH monitoring: is wireless more?
Authors: R H Holloway
Journal: Gut (2005)

Wireless pH monitoring is a significant advance for intraluminal pH recording. It will provide more meaningful data for evaluation of patients and, hopefully, more discriminative diagnosis

Since its introduction in 1974,1 ambulatory oesophageal pH monitoring has secured a valuable but complementary role in the diagnosis of gastro-oesophageal reflux disease. Monitoring of oesophageal pH allows not only the detection of excessive levels of acid exposure but also, and more importantly, assessment of the relationship between acid reflux and symptoms. It is especially useful for clarification of the diagnosis in patients with typical or atypical reflux symptoms who do not response to empirical therapy with a proton pump inhibitor, and for assessment of the level of acid suppression in patients with refractory symptoms or oesophagitis despite appropriate antisecretory therapy.2,3

The traditional method of pH monitoring uses a pH electrode mounted on a catheter that is passed transnasally into the oesophagus and positioned 5 cm above the manometrically defined upper border of the lower oesophageal sphincter. The catheter is connected to a portable data logger thereby allowing ambulatory recordings to be made. Ideally, the circumstances under which the pH recordings are made should reflect, as best as possible, the usual living conditions and physical activities normally undertaken by the patient. However, because the catheter is conspicuous and uncomfortable, most patients restrict their activities and dietary intake,4,5 which could potentially lead to false negative results. In addition, because the electrode is not fixed to the oesophageal wall but rather to the nose, it can become displaced, or transiently “migrate” into the stomach in patients with large mobile hiatus hernias, thereby altering the amount of reflux that is recorded6 and potentially leading to erroneous recordings.7

Recently, a new pH monitoring system has been developed that overcomes these limitations …
Senear-Usher syndrome with parathyroid adenoma
Authors: RODNEY S. W. BASLER
Journal: British Journal of Dermatology (1974)

Journal Article Senear‐Usher syndrome with parathyroid adenoma Get access RODNEY S. W. BASLER RODNEY S. W. BASLER Department of Dermatology, The University of Michigan, Ann Arbor, Michigan 48104, U. S. A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue 4, 1 October 1974, Pages 465–467, https://doi.org/10.1111/j.1365-2133.1974.tb13088.x Published: 01 October 1974 Article history Accepted: 11 January 1974 Published: 01 October 1974
Eosinophilic pneumonia and respiratory failure associated with a trazodone overdose.
Authors: S M Salerno, J S Strong, B J Roth, V Sakata
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Drug-induced eosinophilic lung disease commonly presents as a simple pulmonary eosinophilia-like syndrome consisting of transient pulmonary infiltrates, peripheral eosinophilia, and mild pulmonary symptoms that disappear promptly upon withdrawal of the offending medication. However, a more fulminant presentation most resembling acute eosinophilic pneumonia has been recently described. We present a patient with BAL-confirmed eosinophilic pneumonia (EP) and respiratory failure after a trazodone overdose. This is the first case of EP associated with trazodone and only the third drug-mediated EP reported to precipitate respiratory failure.
Clarification of Anastrozole/Megestrol Acetate Trial Program Design
Authors: Anthony Howell, M. Kaufmann
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.24.4109 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11118472 Clarification of Anastrozole/Megestrol Acetate Trial Program Design Anthony HowellxAnthony HowellSearch for articles by this author M. KaufmannxM. KaufmannSearch for articles by this author Show More Christie Cancer Research Campaign Research Centre Christie Hospital National Health Service Trust Manchester, United KingdomGoethe Universität Frankfurt a. Main Frankfurt/Main, Germany https://doi.org/10.1200/JCO.2000.18.24.4109 Full Text PDF Figures and Tables "Clarification of Anastrozole/Megestrol Acetate Trial Program Design." Journal of Clinical Oncology, 18(24), p. 4109© 2000 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15122000In Reply:The pooled analysis has yielded interesting results, as reviewed by Hamilton and Piccart.1 Hamilton and Piccart’s review concluded the following: No survival advantage for anastrozole was seen in the North American trial. No advantage for anastrozole was seen in any other efficacy end point in the combined analysis. No survival advantage was demonstrated for the higher dose (10 mg) of anastrozole, although there was a trend toward longer survival for the 10-mg dose versus megestrol acetate in the combined trials (P = .09). REFERENCE2. Hamilton A, Piccart M: The third-generation non-steroidal aromatase inhibitors: A review of their clinical benefits in the second-line hormonal treatment of advanced breast cancer. Ann Oncol 10:: 377,1999-384, Crossref, Medline, Google Scholar
Decreased T-suppressor cell activity in rats with adjuvant arthritis.
Authors: L Binderup
Journal: Annals of the Rheumatic Diseases (1983)

Concanavalin-A-induced T-suppressor cell activity was decreased in spleen cell suspensions from Lewis rats with adjuvant arthritis. This decreased activity was evident on day 10 after the induction of the disease, just before the development of the polyarthritic lesions, and persisted during the period of active inflammatory and immunological disease. The extent of the impairment of T-suppressor cell activity was positively correlated with the severity of the arthritic lesions. Removal of phagocytic cells prior to induction of T-suppressor cells abolished the observed decrease in suppressor cell activity. It is suggested that this model may be of value for the investigation of suppressor cell function in immunologically mediated disorders.
Support for the N -Methyl-D-Aspartate Receptor Hypofunction Hypothesis of Schizophrenia From Exome Sequencing in Multiplex Families
Authors: Andrew E. Timms, Michael O. Dorschner, Jeremy Wechsler, Kyu Yeong Choi, Robert Kirkwood, Santhosh Girirajan, Carl Baker, Evan E. Eichler, Olena Korvatska, Katherine W. Roche, Marshall S. Horwitz, Debby W. Tsuang
Journal: JAMA Psychiatry (2013)

<h3>Importance</h3>Schizophrenia is a complex genetic disorder demonstrating considerable heritability. Genetic studies have implicated many different genes and pathways, but much of the genetic liability remains unaccounted for. Investigation of genetic forms of schizophrenia will lead to a better understanding of the underlying molecular pathways, which will then enable targeted approaches for disease prevention and treatment.<h3>Objective</h3>To identify new genetic factors strongly predisposing to schizophrenia in families with multiple affected individuals with schizophrenia.<h3>Design</h3>We performed genome-wide array comparative genomic hybridization, linkage analysis, and exome sequencing in multiplex families with schizophrenia.<h3>Setting</h3>Probands and their family members were recruited from academic medical centers.<h3>Participants</h3>We intended to identify rare disease-causing mutations in 5 large families where schizophrenia transmission appears consistent with single-gene inheritance.<h3>Intervention</h3>Array comparative genomic hybridization was used to identify copy number variants, while exome sequencing was used to identify variants shared in all affected individuals and linkage analysis was used to further filter shared variants of interest. Analysis of select variants was performed in cultured cells to assess their functional consequences.<h3>Main Outcome Measures</h3>Rare inherited disease-related genetic mutations.<h3>Results</h3>No segregating rare copy number variants were detected by array comparative genomic hybridization. However, in all 5 families, exome sequencing detected rare protein-altering variants in 1 of 3 genes associated with the N -methyl-D-aspartate (NMDA) receptor. One pedigree shared a missense and frameshift substitution of GRM5, encoding the metabotropic glutamate receptor subtype 5 (mGluR5), which is coupled to the NMDA receptor and potentiates its signaling; the frameshift disrupts binding to the scaffolding protein tamalin and increases mGluR5 internalization. Another pedigree transmitted a missense substitution in PPEF2, encoding a calmodulin-binding protein phosphatase, which we show influences mGluR5 levels. Three pedigrees demonstrated different missense substitutions within LRP1B, encoding a low-density lipoprotein receptor–related protein tied to both the NMDA receptor and located in a chromosome 2q22 region previously strongly linked to schizophrenia.<h3>Conclusions and Relevance</h3>Exome sequencing of multiplex pedigrees uncovers new genes associated with risk for developing schizophrenia and suggests potential novel therapeutic targets.