tbuckley/cabot-search huggingface dataset:
Exome sequencing identified MYO1E and NEIL1 as candidate genes for human autosomal recessive steroid-resistant nephrotic syndrome
Authors: Simone Sanna-Cherchi, Katelyn E. Burgess, Shannon N. Nees, Gianluca Caridi, Patricia L. Weng, Monica Dagnino, Monica Bodria, Alba Carrea, Maddalena A. Allegretta, Hyunjae R. Kim, Brittany J. Perry, Maddalena Gigante, Lorraine N. Clark, Sergey Kisselev, Daniele Cusi, Loreto Gesualdo, Landino Allegri, Francesco Scolari, Vivette D'Agati, Lawrence S. Shapiro, Carmine Pecoraro, Teresa Palomero, Gian M. Ghiggeri, Ali G. Gharavi
Journal: Kidney International (2011)
Chromosomal Abnormalities in Lymphoma
Authors: A. S. D. Spiers, A. G. Baikie
Journal: BMJ (1965)

Both manufacturers concerned were un- aware of the recommendations or of the use of radiation pressure measurement.Both are discontinuing the models tested and bringing out improved designs.As ultrasound is now being used in destroying nerve tissue in MWniere's disease and in neurosurgery, and much more extensively in diagnosis, the importance of an accurate method of measuring dose is obvious.It is not surprising in view of my measurements that ultrasonic equipment is regarded as witchcraft by many specialists in physical medicine.There is, however, good empirical evidence (Professor A. E.
Review: Preoperative behavioral interventions increase smoking cessation and reduce postoperative complications
Authors: Wesley D. Harden, Allan V. Prochazka
Journal: Annals of Internal Medicine (2014)

ACP Journal Club15 July 2014Review: Preoperative behavioral interventions increase smoking cessation and reduce postoperative complicationsWesley D. Harden, MD, Allan V. Prochazka, MD, MScWesley D. Harden, MDDenver VA Medical Center, Denver, Colorado, USA (W.D.H., A.V.P.)Search for more papers by this author, Allan V. Prochazka, MD, MScDenver VA Medical Center, Denver, Colorado, USA (W.D.H., A.V.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-161-2-201407150-02002 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationThomsen T, Villebro N, Møller AM. Interventions for preoperative smoking cessation. Cochrane Database Syst Rev. 2014(3):CD002294. https://pubmed.ncbi.nlm.nih.gov/24671929Clinical Impact RatingsGIM/FP/GP: Hospitalists: References1 Myers K, Hajek P, Hinds C, McRobbie H. Stopping smoking shortly before surgery and postoperative complications: a systematic review and meta-analysis. Arch Intern Med. 2011;171:983-9. [PMID: 21403009] Google Scholar2 Tobacco Use and Dependence Guideline Panel. Treating Tobacco Use and Dependence: 2008 Update. Rockville, MD: US Department of Health and Human Services. May 2008. http://bphc.hrsa.gov/buckets/treatingtobacco.pdf (accessed 23 May 2014). Google Scholar3 Stead LF, Hartmann-Boyce J, Perera R, Lancaster T. Telephone counselling for smoking cessation. Cochrane Database Syst Rev. 2013(8): CD002850. [PMID: 23934971] Google Scholar Author, Article, and Disclosure InformationAffiliations: Denver VA Medical Center, Denver, Colorado, USA (W.D.H., A.V.P.)This article was published at Annals.org on 1 July 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByImplementing Facilitated Access to a Text Messaging, Smoking Cessation Intervention Among Swedish Patients Having Elective Surgery: Qualitative Study of Patients’ and Health Care Professionals’ PerspectivesMobile Phone–Based Smoking-Cessation Intervention for Patients Undergoing Elective Surgery: Protocol for a Randomized Controlled Trial 15 July 2014Volume 161, Issue 2Page: JC2KeywordsDatabasesDrug therapyHospitalistsNicotine replacement therapySurgerySystematic reviews ePublished: 15 July 2014 Issue Published: 15 July 2014 CopyrightCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Progression of the Lesion at the Site of Inoculation after Smallpox Vaccination
Authors: Kathleen Rubins, David A Relman
Journal: New England Journal of Medicine (2003)

Photographs show the progression of a lesion from vaccination in a healthy, previously unvaccinated 23-year-old woman. Undiluted smallpox vaccine (Dryvax, Wyeth Laboratories) was introduced into the skin of the upper arm by scarification with 15 punctures from a bifurcated needle. Tender axillary lymphadenopathy developed bilaterally on day 6 and was more marked on the ipsilateral side. Erythema and induration were noted from the 8th day after vaccination through the 11th day and measured 10 cm in diameter. On day 9, an erythematous streak appeared, extending anteriorly toward the axilla. Two physicians who examined the patient on day 10 (oral temperature, . . .
Ovarian Cancer Immunotherapy Using PD‐L1 siRNA Targeted Delivery from Folic Acid‐Functionalized Polyethylenimine: Strategies to Enhance T Cell Killing
Authors: Pei Yun Teo, Chuan Yang, Lynsey M. Whilding, Ana C. Parente‐Pereira, John Maher, Andrew J. T. George, James L. Hedrick, Yi Yan Yang, Sadaf Ghaem‐Maghami
Journal: Advanced Healthcare Materials (2015)

Adoptive T cell immunotherapy is a promising treatment strategy for epithelial ovarian cancer (EOC). However, programmed death ligand‐1 (PD‐L1), highly expressed on EOC cells, interacts with programmed death‐1 (PD‐1), expressed on T cells, causing immunosuppression. This study aims to block PD‐1/PD‐L1 interactions by delivering PD‐L1 siRNA, using various folic acid (FA)–functionalized polyethylenimine (PEI) polymers, to SKOV‐3‐Luc EOC cells, and investigate the sensitization of the EOC cells to T cell killing. To enhance siRNA uptake into EOC cells, which over express folate receptors, PEI is modified with FA or PEG–FA so that siRNA is complexed into nanoparticles with folate molecules on the surface. PEI modification with a single functional group lowers the polymer cytotoxicity compared to unmodified PEI. FA‐conjugated polymers increase siRNA uptake into SKOV‐3‐luc cells and decrease unspecific uptake into monocytes. All polymers result in 40% to 50% PD‐L1 protein knockdown. Importantly, SKOV‐3‐Luc cells treated with either PEI–FA or PEI– polyethylene glycol (PEG)–FA/PD‐L1 siRNA complexes are up to twofold more sensitive to T cell killing compared to scrambled siRNA treated controls. These findings are the first to demonstrate that PD‐L1 knockdown in EOC cells, via siRNA/FA‐targeted delivery, are able to sensitize cancer cells to T cell killing.
Regulation by insulin of myocardial glucose and fatty acid metabolism in the conscious dog.
Authors: E J Barrett, R G Schwartz, C K Francis, B L Zaret
Journal: Journal of Clinical Investigation (1984)

In vivo small doses of insulin inhibit lipolysis, lower plasma FFA, and stimulate glucose disposal. Lowering of plasma FFA, either in the absence of a change in insulin or during combined hyperglycemia and hyperinsulinemia, promotes glucose uptake by heart muscle in vivo. In the isolated perfused heart, large doses of insulin directly stimulate heart glucose uptake. To assess the effect of physiological elevations of plasma insulin upon myocardial glucose and FFA uptake in vivo independent of changes in plasma substrate concentration, we measured arterial and coronary sinus concentrations of glucose, lactate, and FFA, and coronary blood flow in conscious dogs during a 30 min basal and a 2 h experimental period employing three protocols: (a) euglycemic hyperinsulinemia (insulin clamp, n = 5), (b) euglycemic hyperinsulinemia with FFA replacement (n = 5), (c) hyperglycemic euinsulinemia (hyperglycemic clamp with somatostatin, n = 5). In group 1, hyperinsulinemia (insulin = 73 +/- 13 microU/ml) stimulated heart glucose uptake (7.3 +/- 4.4 vs. 28.2 +/- 2.8 mumol/min, P less than 0.002), lowered plasma FFA levels by 80% (P less than 0.05), and decreased heart FFA uptake (28.4 +/- 4 vs. 1.5 +/- 0.9, P less than 0.01). When the fall in plasma FFA was prevented by FFA infusion (group 2), hyperinsulinemia (86 +/- 10 microU/ml) provoked a lesser (P less than 0.05) stimulation of glucose uptake (delta = 8.2 +/- 4.2 mumol/min) than in group 1, and there was no significant change in FFA uptake (25.3 +/- 16 vs. 16.5 +/- 4). Hyperglycemia (plasma glucose = 186 +/- 8 mg/100 ml) during somatostatin infusion resulted in only a small rise in plasma insulin (delta = 12 +/- 7 microU/ml), and although plasma FFA tended to decline, heart glucose uptake did not rise significantly (delta = 5.5 +/- 3.2 mumol/min, P = NS). There was no significant change in coronary blood flow during any of the three study protocols. We conclude that, in the dog, insulin at physiologic concentrations: (a) stimulates heart glucose uptake, both directly and by suppressing the plasma FFA concentration, and (b) does not alter coronary blood flow. Hyperglycemia per se has little effect on heart glucose uptake.
Management of Shoulder Dystocia
Authors: Alan Rubin
Journal: JAMA (1964)

Two helpful maneuvers for managing shoulder dystocia, a common cause of fetal injury, are not described in obstetrical texts. In the first, the shoulders are disimpacted by rocking them through the mother's abdominal wall, with the hope that they then will find a more favorable diameter for descent. The second maneuver, performed vaginally, aims at reducing the circumference and transverse diameter of the shoulders. Shoulder dimensions of new born infants placed in the posture imposed by the second maneuver were consistently smaller than those of infants in the position which results when traditional technique is employed.
Reviews and Notes: Geriatrics: Autonomy and Long-Term Care
Authors: John W. Burnside
Journal: Annals of Internal Medicine (1994)

Literature of Medicine1 April 1994Reviews and Notes: Geriatrics: Autonomy and Long-Term CareJohn W. BurnsideJohn W. BurnsideThe University of Texas Southwestern Medical School, Dallas, TX 75235-9005.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-7-199404010-00030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Autonomy and Long-Term CareGeorge J. Agich. 197 pages. New York: Oxford University Press; 1993. $35.00.Autonomy is perhaps the youngest of the four prima facie values that constitute the major concerns of medical ethicists today. The paradigm circumstance of informed consent necessarily led us to consider autonomy in the context of decisions and actions.For most of us, the notion of long-term care connotes severe limitations of mental activity and mobility, making autonomy and long-term care seem mutually exclusive or perhaps oxymoronic. Not so, argues Dr. Agich. He modestly contends that his treatise explores the circumstances of long-term care ... Author, Article, and Disclosure InformationAffiliations: The University of Texas Southwestern Medical School, Dallas, TX 75235-9005. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1994Volume 120, Issue 7Page: 623-624KeywordsDecision makingGeriatricsLong-term careWheelchairs ePublished: 15 August 2000 Issue Published: 1 April 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Pulmonary hyperplasia and the two sides of PKC 
Authors: K. Graf
Journal: Cardiovascular Research (2008)

Protein kinase C (PKC) was initially identified by Nishizuka and coworkers1 as a nucleotide-independent, Ca2+-dependent serine kinase. Molecular cloning identified at least 11 isozymes of PKC that were further divided into subfamilies based on sequence homology and mode of stimulation. The classical PKCs (α, βI, βII, and γ) are diacylglycerol (DAG) and calcium-dependent enzymes, whereas the novel PKCs (δ, e, θ, and η) require DAG, but not calcium, for activation. The atypical PKCs (ζ, ι/λ) are not responsive to activation by DAG or calcium, but are activated by other lipid-derived second messengers. PKCs contain N-terminal regulatory and C-terminal catalytic domains separated by a flexible hinge region. In the absence of activating cofactors, the catalytic domain is subject to autoinhibition by the regulatory domain that is mediated, in part, by a pseudosubstrate sequence motif resembling the consensus sequence for phosphorylation by PKC.2 PKCs in general are involved in multiple intracellular … 

*Corresponding author. Tel: +49 30 4593 2413; fax: +49 30 4593 2415. E-mail address : graf{at}dhzb.de
Abstract 116: A novel methodology for analyzing post-processed LC/MS metabolomics data
Authors: Tytus Mak, John B. Tyburski, John F. Kalinich, Albert J. Fornace
Journal: Cancer Research (2010)

Abstract Metabolomics, the global study of small molecule complements, shows great promise as a tool for the discovery of biomarkers of mutagen exposure and early tumorigenesis. With the ever increasing pool of quantitative data yielded from metabolomic research, methods and tools with which to analyze and extract meaningful conclusions from these data are becoming more and more crucial. Methods currently in wide use are limited in either the scope and depth of analysis or are not specifically tailored to metabolomic datasets. In light of this, a new methodology has been developed and presented here that is specifically tailored to characteristics unique to post-processed LC/MS metabolomic data acquired from biofluid samples. For this study, twenty-four-hour urine samples were collected from male rats before and after whole body exposures to doses of gamma radiation ranging from 0.5 to 10 Gy (n = 20 per dose). Urine metabolomics data were acquired by Ultra-Performance Liquid Chromatography coupled to time-of-flight mass spectrometry, operated in both positive and negative electrospray ionization modes, and pre-processed using MarkerLynx software (Waters, Inc.). Relative abundances of urinary ions were normalized to corresponding creatinine relative abundances to reduce the probability of confounding by variation in renal function. These data were then used to develop our methodology, which can be used as a visualization tool effective in qualitatively illustrating an overall metabolome response to radiation exposure. This is achieved by creating 3D plots, on which each plotted point represents a metabolite, specified by its mass/charge (X axis) and retention time (Y axis), with its pre- to post-exposure change in regulation (Z axis) colorized with regard to the magnitude of change. In addition, numerous data filters and data augmentation schemes, such as noise filters, were developed in order to yield results that were more quantitatively robust, from which stronger conclusions can be drawn about the experiment, such as identifying specific metabolites of interest. With the development of this methodology, the repertoire of analytical tools available to metabolomics researchers will be enhanced, facilitating more rapid and meaningful biomarker discovery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 116.
The Radionuclide Ventriculogram
Authors: Steven M. Larson
Journal: JAMA (1973)

Radionuclide ventriculography is a safe and effective method for evaluating cerebrospinal fluid (CSF) dynamics. Seventy radionuclide ventriculograms from 47 patients were reviewed. The patients were primarily adults with acquired disorders, such as intracerebral neoplasm, meningeal infection, and low pressure hydrocephalus. Proper interpretation depended on an understanding of ventricular anatomy and the usual sequence of CSF flow. Important applications were assessment of CSF shunts, determination of the distribution of intrathecally administered drugs, evaluation of the functional status of hydrocephalus, and assessment of the progression of neoplastic invasion of the ventricular system.
Expression of cell membrane complement regulatory glycoproteins along the normal and diseased human gastrointestinal tract
Authors: A E Berstad, P Brandtzaeg
Journal: Gut (1998)

<i>Background/Aims</i>—Uncontrolled complement activation may be of immunopathological importance in inflammatory diseases of the gastrointestinal tract. Expression of membrane bound factors that regulate complement activation was therefore studied in situ. <i>Methods</i>—Frozen tissue specimens were obtained from patients with <i>Helicobacter pylori</i> gastritis, coeliac disease, Crohn's disease, or ulcerative colitis, and from histologically normal controls. Sections were examined by immunofluorescence with monoclonal antibodies to protectin (CD59), decay accelerating factor (DAF), and membrane cofactor protein (MCP). <i>Results</i>—Protectin and MCP were widely expressed in normal and diseased mucosae. MCP was generally observed basolaterally on all epithelial cells, whereas apical protectin expression was more intense on the epithelium of normal colonic mucosa than in the normal duodenum (p = 0.001). Epithelial DAF and to some extent protectin were upregulated in gastritis, coeliac disease, and inflammatory bowel disease. Areas of the stomach with intestinal metaplasia expressed DAF, unlike the adjacent gastric epithelium. Parietal cells of the gastric body expressed neither protectin nor DAF. <i>Conclusion</i>—Epithelial complement inhibitory molecules were expressed differently at various normal gastrointestinal sites and also in association with mucosal disease, suggesting variable protective potential. Such molecules could play a role in the development of gastric atrophy by protecting areas of intestinal metaplasia. Conversely, parietal cells appeared to be potentially vulnerable targets for complement attack.
Reply to U. Dührsen et al
Authors: Marinus H. J. van Oers, Evelyn Tönnissen, Martine Van Glabbeke, Livia Giurgea, Joop H. Jansen, Richard Klasa, Robert E. Marcus, Max Wolf, Eva Kimby, Andrej Vranovsky, Harald Holte, Anton Hagenbeek, Bert A. van der Reijden
Journal: Journal of Clinical Oncology (2010)

In their letter, Duhrsen et al disagree with our conclusion that in patients with relapsed or refractory follicular lymphoma, the presence of tumor cells in blood or bone marrow, as detected by BCL2/IgH major break point region (MBR) polymerase chain reaction (PCR) at the end of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone induction therapy, is not predictive of progression-free survival (PFS). Their major argument is that we have compared inappropriate groups because the BCL2/IgH MBR–negative group might have contained patients with tumor cells in blood or bone marrow that have escaped detection because they have t(14;18) with a break point outside the MBR. On the basis of cited literature, they mention that up to 50% of t(14;18) patients have break points outside the MBR, whereas in fact, this figure is 32%. Nevertheless, regardless of the exact frequency of BCL2/ IgHMBRpositivityamongpatientswitht(14;18), intheDiscussionofour article, we already have addressed rather extensively the issue raised by Duhrsen et al. At present, we are in the process of performing an additional minor break point region PCR analysis to further corroborate our conclusions. However, when we restricted our analysis to the group with initial BCL2/IgH MBR–positive results in blood and/or bone marrow, we found no difference in PFS between patients who converted from PCR positive to PCR negative and patients who remained PCR positive. This was true for both bone marrow and peripheral blood. This observation, which was mentioned in our article under Results, strongly supports the conclusion that in patients with relapsed or refractory follicular lymphoma, the BCL2/IgH status in peripheral blood and bone marrow at the end of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone induction therapy is not predictive for PFS.
Treating IIA/B Seminoma With Combination Carboplatin and Radiotherapy
Authors: Duncan C. Gilbert, Nicholas J. VanAs, Sharon Beesley, David Bloomfield, Julian Money-Kyrle, Andy Norman, David Dearnaley, Alan Horwich, Robert A. Huddart
Journal: Journal of Clinical Oncology (2009)

regarding the systemic reform of clinical trials.Taking these facts into consideration, to enhance public understanding regarding clinical trials, it may be important to utilize means of providing information other than newspapers, which often emphasize medication scandals and misconduct.Our study shows that clinical trials are topics that the major newspapers report.However, many of the newspaper reports emphasize the performance of pharmaceutical companies and incidents of misconduct, such as medication scandals, while providing insufficient information regarding the system of clinical trials.It is recommended that health care professionals fully understand these characteristics of the major newspapers.
Xanthine Oxidase Inhibition Reverses Endothelial Dysfunction in Heavy Smokers
Authors: Sashi Guthikonda, Christine Sinkey, Therese Barenz, William G. Haynes
Journal: Circulation (2003)

Background— Cigarette smoking causes endothelial dysfunction, possibly through increased oxidant stress. The enzyme xanthine oxidase produces oxidative free radicals. We tested the hypothesis that xanthine oxidase contributes to endothelial dysfunction in cigarette smokers by administering the inhibitor allopurinol. Methods and Results— Fourteen cigarette smokers (31±4 pack years) and 14 age- and sex-matched healthy non-smoking control subjects participated in a single-blinded, randomized, 2-phase crossover study. All subjects had no other risk factors for atherosclerosis. Inhibition of xanthine oxidase was achieved by a single oral dose of 600 mg of allopurinol on the day of the study. Stimulated nitric oxide endothelial responses were assessed by forearm blood flow responses to intraarterial administration of acetylcholine and bradykinin 4 to 7 hours later; basal nitric oxide was assessed using the nitric oxide synthase inhibitor NG-monomethyl- l -arginine (L-NMMA); and nitroprusside was used to assess sensitivity to nitric oxide. Dilatation produced by acetylcholine was significantly less in smokers (254±57%) than healthy controls (390±55%) ( P =0.009). Allopurinol reversed endothelial dysfunction in smokers (acetylcholine, 463±78%, P =0.001) without affecting responses in non-smokers (401±80%). Bradykinin responses were also impaired in smokers ( P =0.003), and improved with allopurinol, though not significantly ( P =0.06). Responses to nitroprusside and L-NMMA were not significantly different between smokers and controls and were not altered by allopurinol. Conclusions— Smoking-induced endothelial dysfunction of resistance vessels is rapidly reversed with oral allopurinol. These data suggest that xanthine oxidase contributes importantly to endothelial dysfunction caused by cigarette smoking.
Managing chronic myeloid leukemia patients intolerant to tyrosine kinase inhibitor therapy
Authors: D J DeAngelo
Journal: Blood Cancer Journal (2012)

The outcomes for patients with chronic myeloid leukemia have improved dramatically with the development and availability of BCR-ABL1 tyrosine kinase inhibitors (TKIs) over the past decade. TKI therapy has a superior safety profile compared with the previous standard of care, interferon-α, and most adverse events (AEs) observed with front-line and second-line TKI treatment are managed with supportive care. However, some patients are intolerant to TKI therapy and experience AEs that cannot be managed through dose reduction or symptomatic treatment. Careful management of AEs helps patients to remain adherent with treatment and increases their chances for successful outcomes. Proactive vigilance for potential AEs and treatment strategies that reduce symptom burden will help to minimize patient intolerance. This review discusses the most common AEs associated with intolerance to TKI therapy and treatment strategies to help manage patients at risk for or experiencing these events.