tbuckley/cabot-search huggingface dataset:
Serum proteomics and biomarker discovery across the spectrum of nonalcoholic fatty liver disease
Authors: Lauren N. Bell, Janice L. Theodorakis, Raj Vuppalanchi, Romil Saxena, Kerry G. Bemis, Mu Wang, Naga Chalasani
Journal: Hepatology (2009)

Nonalcoholic fatty liver disease (NAFLD), ranging from relatively benign simple steatosis to progressive nonalcoholic steatohepatitis (NASH) and fibrosis, is an increasingly common chronic liver disease. Liver biopsy is currently the only reliable tool for staging the subtypes of NAFLD; therefore, noninvasive serum biomarkers for evaluation of liver disease and fibrosis are urgently needed. We performed this study to describe changes in the serum proteome and identify biomarker candidates in serum samples from 69 patients with varying stages of NAFLD (simple steatosis, NASH, and NASH with advanced bridging [F3/F4] fibrosis) and 16 obese controls. Using a label-free mass spectrometry-based approach we identified over 1,700 serum proteins with a peptide identification (ID) confidence level of &gt;75%, 605 of which changed significantly between any two patient groups (false discovery rate &lt;5%). Importantly, expression levels of 55 and 15 proteins changed significantly between the simple steatosis and NASH F3/F4 group and the NASH and NASH F3/F4 group, respectively. Classification of proteins with significant changes showed involvement in immune system regulation and inflammation, coagulation, cellular and extracellular matrix structure and function, and roles as carrier proteins in the blood. Further, many of these proteins are synthesized exclusively by the liver and could potentially serve as diagnostic biomarkers for identifying and staging NAFLD. Conclusion : This proteomic analysis reveals important information regarding the pathogenesis/progression of NAFLD and NASH and demonstrates key changes in serum protein expression levels between control subjects and patients with different stages of fatty liver. Future validation of these potential biomarkers is needed such that these proteins may be used in place of liver biopsy to facilitate diagnosis and treatment of patients with NAFLD. (Hepatology 2009.)
Liver Biopsy in Hodgkin's Disease
Authors: CHARLES M. BAGLEY
Journal: Annals of Internal Medicine (1972)

Liver biopsy sections of 127 patients (89 without previous therapy) were classified for the presence of Reed-Sternberg cells and other cellular infiltrates and abnormalities. These histologic findings were then correlated with the clinical and laboratory findings in each patient. In seven of eight biopsies with atypical reticulum cell infiltrates, Reed-Sternberg cells could be found if sufficient sections were examined. All other cell infiltrates and pathologic changes showed no correlation with Reed-Sternberg cells or clinical findings. The frequency of positive biopsies was approximately doubled by performing laparotomy or peritoneoscopy after a percutaneous biopsy was negative. Clinical examination of the liver and liver function tests, including alkaline phosphatase and sulfobromophthalein, were of little value in predicting positive findings; abnormalities in these tests may be indicators of a nonspecific hepatic reaction to the presence of Hodgkin's disease elsewhere in the patient. However, patients with splenomegaly had a high risk of liver involvement.
Abstract 4280: Color-coded <i>in vivo</i> imaging of tumor stem cells and co-implanted non-stem cancer cells
Authors: Atsushi Suetsugu, Yosuke Osawa, Mashito Nagaki, Hisataka Moriwaki, Michael Bouvet, Robert M. Hoffman
Journal: Cancer Research (2010)

Abstract We have developed color-coded simultaneous imaging of tumor growth, metastasis and drug resistance of co-implanted cancer stem cells (CSC) and non stem cancer cells (NSCC). In this study, CD 133+ Huh-7 human hepatoma cells were considered as liver cancer CSC, and CD133− Huh-7 cells were considered liver cancer NSCC. CD133+ cells were isolated by magnetic bead sorting. CSC were labeled with GFP and NSCC were labeled with RFP using retroviruses. The same number of GFP CSC and the RFP NSCC were mixed and co-cultured or injected subcutaneously or in the spleen of nude mice. CSC had higher proliferative potential compared with NSCC in vitro. Dual-color imaging demonstrated that CSC were more tumorigenic and more resistant to chemotherapy in vivo than NSCC. To compare the effect of CSC and NSCC on stromal cells or blood vessels in tumors, non-colored CSC or NSCC along with RFP stromal cells were implanted into nestin driven (ND)-GFP transgenic nude mice which express ND-GFP in nascent blood vessels. Extensive RFP-expressing stromal and GFP-expressing nascent blood vessels cells were imaged in the tumors formed from CSC. Tumors formed from NSCCs had less GFP-expressing nascent blood vessels and RFP-expressing stromal cells suggesting that more stromal cells and blood vessels were induced by CSC than NSCC. Thus, liver cancer CSC have more malignant characteristics such as higher proliferation, more resistance to chemotherapy, and induction of stromal cells and blood vessels compared with NSCC. Color-coded imaging of CSC and NSCC is a powerful tool to investigate the characteristics and roles of CSC and NSCC in tumor progression. 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 4280.
IgE antibodies to recombinant pollen allergens (Phl p 1, Phl p 2, Phl p 5, and Bet v 2) account for a high percentage of grass pollen–specific IgE☆☆☆★★★
Authors: Verena Niederberger, Sylvia Laffer, Renate Fröschl, Dietrich Kraft, Helmut Rumpold, Sonja Kapiotis, Rudolf Valenta, Susanne Spitzauer
Journal: Journal of Allergy and Clinical Immunology (1998)
Liver Biopsy and the Alcoholic Patient
Authors: A. SIDNEY BARRITT
Journal: Annals of Internal Medicine (1977)

Letters and Corrections1 July 1977Liver Biopsy and the Alcoholic PatientA. SIDNEY BARRITT III, M.D.A. SIDNEY BARRITT III, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-87-1-121_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I agree with the basic points of Dr. Gordis' editorial, "What is Alcoholism Research?" (Ann Intern Med 85:821-823, 1976), but some of Dr. Cantor's comments in his letter, "Who Will Care For The Alcoholic Patient?" (Ann Intern Med 86:362, 1977), bother me.I agree that the physician's attitude toward the alcoholic patient can inhibit adequate evaluation, but it strikes me that the advocacy of liver biopsy to make a precise diagnosis is not an appropriate measure of the physician's completeness. The axiom that making a precise tissue diagnosis in the alcoholic with liver disease leads to improved... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: A. SIDNEY BARRITTIII, M.D.Affiliations: Veterans Administration Hospital Salem, VA 24153 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1977Volume 87, Issue 1Page: 121-121KeywordsAlcoholicsAlcoholismBiopsyLiverLiver diseasesPatient advocacy ePublished: 1 December 2008 Issue Published: 1 July 1977 PDF downloadLoading ...
Systemic and local determinant factors of coronary artery compliance: An in vivo intravascular ultrasound study
Authors: Toshihiko Nishioka, Osamu Sasaki, Takashi Akima, Shuichi Katsushika, Bonpei Takase, Akira Kurita, Fumitaka Ohsuzu, Nobuo Yoshimoto
Journal: Journal of the American College of Cardiology (2003)
1240 ANALYSIS OF COMPLEX MUTATION PATTERNS IN THE HCV QUASISPECIES OF PATIENTS TREATED WITH TELAPREVIR OR BOCEPREVIR
Authors: S. Susser, S.-E. Schelhorn, C.M. Lange, C. Welsch, J. Vermehren, C. Füller, S. Zeuzem, T. Lengauer, C. Sarrazin
Journal: Journal of Hepatology (2011)
Impact of acute and chronic graft-versus-host disease on human B-cell generation and replication
Authors: Salomé Glauzy, Juliette Soret, Isabelle Fournier, Corinne Douay, Hélène Moins-Teisserenc, Régis Peffault de Latour, Guitta Maki, Marie Robin, Gérard Socié, Antoine Toubert, Emmanuel Clave
Journal: Blood (2014)
Cardiac G-Protein–Coupled Receptor Kinase 2 Ablation Induces a Novel Ca <sup>2+</sup> Handling Phenotype Resistant to Adverse Alterations and Remodeling After Myocardial Infarction
Authors: Philip W. Raake, Xiaoying Zhang, Leif E. Vinge, Henriette Brinks, Erhe Gao, Naser Jaleel, Yingxin Li, Mingxin Tang, Patrick Most, Gerald W. Dorn, Steven R. Houser, Hugo A. Katus, Xiongwen Chen, Walter J. Koch
Journal: Circulation (2012)

Background— G-protein–coupled receptor kinase 2 (GRK2) is a primary regulator of β-adrenergic signaling in the heart. G-protein–coupled receptor kinase 2 ablation impedes heart failure development, but elucidation of the cellular mechanisms has not been achieved, and such elucidation is the aim of this study. Methods and Results— Myocyte contractility, Ca 2+ handling and excitation-contraction coupling were studied in isolated cardiomyocytes from wild-type and GRK2 knockout (GRK2KO) mice without (sham) or with myocardial infarction (MI). In cardiac myocytes isolated from unstressed wild-type and GRK2KO hearts, myocyte contractions and Ca 2+ transients were similar, but GRK2KO myocytes had lower sarcoplasmic reticulum (SR) Ca 2+ content because of increased sodium-Ca 2+ exchanger activity and inhibited SR Ca 2+ ATPase by local protein kinase A–mediated activation of phosphodiesterase 4 resulting in hypophosphorylated phospholamban. This Ca 2+ handling phenotype is explained by a higher fractional SR Ca 2+ release induced by increased L-type Ca 2+ channel currents. After β-adrenergic stimulation, GRK2KO myocytes revealed significant increases in contractility and Ca 2+ transients, which were not mediated through cardiac L-type Ca 2+ channels but through an increased SR Ca 2+ . Interestingly, post-MI GRK2KO mice showed better cardiac function than post-MI control mice, which is explained by an improved Ca 2+ handling phenotype. The SR Ca 2+ content was better maintained in post-MI GRK2KO myocytes than in post-MI control myocytes because of better-maintained L-type Ca 2+ channel current density and no increase in sodium-Ca 2+ exchanger in GRK2KO myocytes. An L-type Ca 2+ channel blocker, verapamil, reversed some beneficial effects of GRK2KO. Conclusions— These data argue for novel differential regulation of L-type Ca 2+ channel currents and SR load by GRK2. G-protein–coupled receptor kinase 2 ablation represents a novel beneficial Ca 2+ handling phenotype resisting adverse remodeling after MI.
The Catarrhal Child
Authors: D. H. Garrow
Journal: BMJ (1965)

Most infections of the upper respiratory tract are due to viruses. They are very common. A child who catches six infections a year is getting no more than his ration. Some children have more than this and seem scarcely ever to be free from symptoms. Apart from runny noses and sore throats there are many respiratory symptoms that do not seem to be related directly to infections : children snore at night or have an irritating cough, they may not listen to what they are told and so seem deaf, they sniff and refuse to use a handkerchief, or their mouths hang open in a vacant way. Some learn to speak late or indistinctly. Plump, relatively compliant infants turn into skinny, disobedient pre-school children, with wills of their own and ribs that stick out reproachfully. Illogically and absurdly catarrh is blamed for all these things and a fictitious image is conjured up of  the catarrhal child. Children rarely complain of respiratory symptoms. They seem quite unconcerned that mucus or mucopus should dribble down their upper lips. It is their parents who are upset, nagging at them to use their handkerchiefs. Many children cough at night without waking, but parents stay awake listening, wondering what it may mean. Snoring never bothered the snorer, and a  sore throat  is often what we doctors see when we peer between resistant lips seeking an explanation for some pyrexia.
ABC of Sports Medicine: Head Injury In Sport
Authors: G McLatchie, B Jennett
Journal: BMJ (1994)

Most sports related injuries are musculoskeletal, affecting limbs or trunk, and related to specific risks associated with particular sports. Head injuries by contrast can occur in many sports and, except those incurred during boxing, are accidental. Unlike other injuries, the effects of which are usually maximal at onset, injury to the head may precipitate a process of intracranial disorder that can convert a mild initial injury into a life threatening condition from secondary complications. Moreover, even mild injuries are often associated with considerable temporary disability, and repeated mild injuries can result in cumulative brian damage. Doctors on sports fields have to decide whether patients with head injury can resume play or, if not, what further immediate management is needed and when they can play again. The answers to these questions depend on a sensible balancing of risks.

It is damage to the brain that matters when the head is hit. Injuries to the scalp or skull are important only as indicators of the possibility of underlying impact damage or of the risk of complications that could cause secondary brain damage. Either impact or secondary brain damage may be diffuse or focal, and this will influence the clinical features.

(1) Cerebral contusions - Bruising on the brain surface due to the brain's impact with the overlying skull - are the commonest form of impact damage. Contusion may be focal underneath a fracture resulting from a focal impact, blunt or penetrating, or it may be diffuse, resulting from the brain as a whole being thrown against the rough interior surface of the skull and dural dividers. Diffuse contusion results when the head as a whole decelerates, usually by hitting the ground, in which case the contusions are usually bilateral, affecting the tips of both frontal and temporal poles regardless of where the …
The Least of These My Brethren: A Doctor's Story of Hope and Miracles on an Inner-City AIDS Ward
Authors: William G. Porter
Journal: JAMA (1997)

As I read this memoir of a doctor's work on an AIDS ward in an inner-city Catholic hospital, I was reminded of a recent newspaper article about a 46-year-old physician who had given up his practice to become a Roman Catholic priest. When asked why, he replied that the spiritual needs of his patients required his attention more than their medical problems. Perhaps so. David Loxterkamp, a family physician in rural Maine, writes about a patient who came to his office to tell him, in the midst of a hectic day, about her unhappy childhood at the hand of an unloving mother. "Is there something you want from me, Mirabelle?" the doctor asked. "Why did you tell me this today?" "Because the priest is out of town and somebody needed to know," she answered.<sup>1</sup> As its title suggests, Daniel Baxter's story invites comparison to the spiritual and medical
Growing trend for trials of new cancer drugs to stop early, review shows
Authors: Susan Mayor
Journal: BMJ (2008)

Growing numbers of clinical trials of new cancer drugs are being stopped prematurely because they are showing early benefit, a review of trials in the past 10 years has shown ( Annals of Oncology 2008 Feb 29; doi: 10.1093/annonc/mdn042).

The study’s authors fear that this could result in a systematic overstatement of the clinical benefits, which may affect decisions by drug regulatory bodies to authorise the drugs and by doctors in their management of patients.

The review analysed 25 randomised controlled trials of new cancer drugs that were stopped early because interim analysis showed benefit, published between 1997 and 2007. It showed that this was a growing trend, with 56% of the studies being stopped early in the past three years (2005-7).

More than three quarters (79%) of the studies …
Extremely low birth weight is linked to risk of chronic illness
Authors: Susan Mayor
Journal: BMJ (2005)

<h3>ABSTRACT</h3> The catalytic site of most enzymes can essentially deal with only one substrate. In contrast, the ribosome is capable of polymerizing at a similar rate at least 20 different kinds of amino acids from aminoacyl-tRNA carriers while using just one catalytic site, the peptidyl-transferase center (PTC). An induced-fit mechanism has been uncovered in the PTC, but a possible connection between this mechanism and the uniform handling of the substrates has not been investigated. We present an analysis of published ribosome structures supporting the hypothesis that the inducedfit eliminates unreactive rotamers predominantly populated for some A-site aminoacyl esters before induction. We show that this hypothesis is fully consistent with the wealth of kinetic data obtained with these substrates. Our analysis reveals that induction constrains the amino acids into a reactive conformation in a side-chain independent manner. It allows us to highlight the rationale of the PTC structural organization, which confers to the ribosome the very unusual ability to handle large as well as small substrates.
Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril.
Authors: M St John Sutton, M A Pfeffer, T Plappert, J L Rouleau, L A Moyé, G R Dagenais, G A Lamas, M Klein, B Sussex, S Goldman
Journal: Circulation (1994)

Left ventricular enlargement after myocardial infarction increases the likelihood of an adverse outcome. In an echocardiographic substudy of the Survival and Ventricular Enlargement (SAVE) Trial, we assessed whether captopril would attenuate progressive left ventricular enlargement in patients with left ventricular dysfunction after acute myocardial infarction and, if so, whether this would be associated with improved clinical outcome.Two-dimensional transthoracic echocardiograms were obtained in 512 patients at a mean of 11.1 +/- 3.2 days after infarction and were repeated at 1 year in 420 survivors. Left ventricular size was assessed as left ventricular cavity areas at end diastole and end systole and left ventricular function as percent change in cavity area from end diastole to end systole. Patients were randomly assigned to placebo or captopril, and the incidence of adverse cardiovascular events consisting of cardiovascular death, heart failure requiring either hospitalization or open-label angiotensin-converting enzyme inhibitor therapy, and recurrent infarction were determined over a follow-up period averaging 3.0 +/- 0.6 years. Irrespective of treatment assignment, baseline left ventricular systolic area and percent change in area were strong predictors of cardiovascular mortality and adverse cardiovascular events. At 1 year, left ventricular end-diastolic and end-systolic areas were larger in the placebo than in the captopril group (P = .038, P = .015, respectively), and percent change in cavity area was greater in the captopril group (P = .005). One hundred eleven of the 420 1-year survivors with 1-year echo measurements (26.4%) experienced a major adverse cardiovascular event, and these patients had more than a threefold greater increase in left ventricular cavity areas than those with an uncomplicated course. Sixty-nine patients with adverse cardiovascular events were in the placebo group compared with 42 patients in the captopril-treated group (a risk reduction of 35%, P = .010).Two-dimensional echocardiography provides important and independent prognostic information in patients after infarction. Left ventricular enlargement and function after infarction are associated with the development of adverse cardiac events. Attenuation of ventricular enlargement with captopril in these patients was associated with a reduction in adverse events. This study demonstrates the linkage between attenuation of left ventricular enlargement by captopril after infarction and improved clinical outcome.
Research with unaccompanied children seeking asylum
Authors: S. Thomas
Journal: BMJ (2003)

Research into the needs of lone asylum seeking and refugee children must be sensitive and appropriate to avoid causing more harm to a vulnerable population 

The rise in the refugee and asylum seeking populations in the United Kingdom has led to increased research and debate about their health and social needs. Although more information is needed, concerns exist that some researchers may be unaware of the complex issues inherent in conducting research with such groups. Language, culture, religion, social norms, and experiences of oppression may make it difficult to obtain truly informed and voluntary consent or truly accurate responses to research questions. In addition, refugees may be stigmatised or risk reprisal merely by entering a study.1 These concerns are magnified for young people who are refugees or seeking asylum, particularly those who arrive in the United Kingdom alone. We have drawn on our experience working with unaccompanied children who are seeking asylum to suggest guidelines for researchers.

Unaccompanied, asylum seeking children are defined as those who are younger than 18 years old who have been separated from both parents and are not being cared for by an adult who, by law or custom, has a responsibility to do so. In recent years, the number of unaccompanied children arriving in the United Kingdom has increased, with almost 3500 asylum applications in 2001 compared with 2700 in 2000.2 The main countries of origin were Afghanistan, former Yugoslavia, Somalia, and Iraq.

Research into the needs of children seeking asylum is essential to improve their care (box 1) but can be harmful unless conducted appropriately. The guidelines of the ethics committee of the Royal College of Paediatrics and Child Health state that children are a unique research group who are particularly vulnerable, easily bewildered and frightened, and unable to express their needs …
Vascular Access for Cancer Chemotherapy
Authors: Robert M. Steckler
Journal: JAMA (1977)

<h3>To the Editor. —</h3> I read with interest the paper entitled "Vascular Access for Cancer Chemotherapy" by Lempert, Knight, and Karmody (237:1964, 1977). The procedure they describe for improving vascular access for cancer chemotherapy was first described in the<i>Southern Medical Journal</i>in July 1974.<sup>1</sup>In this report, we described our experience with 26 patients in whom arteriovenous fistulas were created to improve vascular access for chemotherapy. We emphasized that the fistula should be created before the difficulties with vascular access arise. In this way a bovine graft can be avoided, and equally good, if not superior, results can be obtained with a smaller surgical procedure. In patients undergoing long-term chemotherapy with the accompanying leukopenia, the resistance to infection is almost always decreased. The magnitude of any surgical procedure in these patients should be minimized in view of the risks of sepsis, morbidity, and even mortality.
Indoor Environmental Exposures for Children with Asthma Enrolled in the HEAL Study, Post-Katrina New Orleans
Authors: L. Faye Grimsley, Patricia C. Chulada, Suzanne Kennedy, LuAnn White, Jeremy Wildfire, Richard D. Cohn, Herman Mitchell, Eleanor Thornton, Jane El-Dahr, Mosanda M. Mvula, Yvonne Sterling, William J. Martin, Kevin U. Stephens, Maureen Lichtveld
Journal: Environmental Health Perspectives (2012)

Rain and flooding from Hurricane Katrina resulted in widespread growth of mold and bacteria and production of allergens in New Orleans, Louisiana, which may have led to increased exposures and morbidity in children with asthma.
Intravitreal Aflibercept (VEGF Trap-Eye) in Wet Age-related Macular Degeneration
Authors: Jeffrey S. Heier, David M. Brown, Victor Chong, Jean-Francois Korobelnik, Peter K. Kaiser, Quan Dong Nguyen, Bernd Kirchhof, Allen Ho, Yuichiro Ogura, George D. Yancopoulos, Neil Stahl, Robert Vitti, Alyson J. Berliner, Yuhwen Soo, Majid Anderesi, Georg Groetzbach, Bernd Sommerauer, Rupert Sandbrink, Christian Simader, Ursula Schmidt-Erfurth
Journal: Ophthalmology (2012)