tbuckley/cabot-search huggingface dataset:
Roles of hypoxia-inducible factor-1α (HIF-1α) versus HIF-2α in the survival of hepatocellular tumor spheroids
Authors: Heidi Menrad, Christian Werno, Tobias Schmid, Ekaterini Copanaki, Thomas Deller, Nathalie Dehne, Bernhard Brüne
Journal: Hepatology (2010)

Hypoxia-inducible factors (HIFs) provoke adaptation to hypoxic stress occurring in rapidly growing tumor tissues. Therefore, overexpression of HIF-1 or HIF-2 is a common feature in hepatocellular carcinoma but their specific function is still controversially discussed. To analyze HIF function in hypoxia-induced cell death we created a stable knockdown of HIF-1α and HIF-2α in HepG2 cells and generated tumor spheroids as an in vitro hepatocellular carcinoma model. Knockdown of HIF-1α enhanced expression of HIF-2α and vice versa. Unexpectedly, knockdown of HIF-1α or HIF-2α increased cell viability as well as spheroid size and decreased caspase-3 activity. Antiapoptotic Bcl-XL expression increased in both knockdown spheroids, whereas proapoptotic Bax was only reduced in HIF-1α-knockdown cells. Furthermore, an HIF-2α-knockdown significantly increased Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression in an HIF-1α-dependent manner. Concomitantly, electron microscopy revealed a substantial increase in autophagosomal structures in HIF-2α-knockdown spheroids and mito-/lysotracker costaining confirmed lysosomal activity of these autophagosomes. Blocking autophagosome maturation using 3-methyladenine restored cell death in HIF-2α-knockdown clones comparable to wildtype cells. Conclusion : An HIF-1α-knockdown increases HIF-2α expression and shifts the balance of Bcl-2 family members toward survival. The knockdown of HIF-2α raises autophagic activity and attenuates apoptosis by enhancing HIF-1α expression. Our data indicate that enhanced expression of one HIF-isoform causes a survival advantage in hepatocellular carcinoma development. Hepatology 2010
Alimentary Canal: Intestinal Absorption
Authors: Sumner C. Kraft
Journal: JAMA (1968)

This comprehensive volume on intestinal absorption is one of five devoted to the alimentary canal. When completed, the multisectioned handbook is intended to provide a critical survey of all areas of modern physiology. This particular review seeks to orient graduates, to aid teachers, and to provide source material for students and research workers seeking to correlate their observations with those of others. Many of the 17 authoritative chapters are written by physician-physiologists who maintain a good balance between basic physiological knowledge and concepts and applications to clinical problems. In addition to clearly written discussions on the intestinal absorption of specific moieties, important introductory chapters describe the development of intestinal structure and function, the morphology of the gut epithelium, general principles of transport across membranes, and a rather detailed survey of how to investigate intestinal absorption. The lucidity of the book is enhanced by many tables, diagrams, graphs, and light and
An Appraisal of Long-Term Results in Surgical Treatment of Breast Cancer
Authors: Edward F. Lewison
Journal: JAMA (1963)

The results of the surgical treatment of breast cancer at the Johns Hopkins Hospital revealed that the five-year survival rate for radical mastectomy was 52% and the ten-year survival rate was 33%. These results were reviewed and compared with prior time periods and only a slight increase in the survival rate was noted. The most impressive feature of the surgical treatment of breast cancer is the striking similarity and surprising uniformity of long-term end results despite widely differing therapeutic techniques as reported from this country and abroad. Further comparisons between individual series differing in composition, classification, and case selection will never resolve our divergent differences of opinion. There is an urgent need for a large cooperative and randomized clinical trial designed biometrically to compare the results of alternative and equivalent surgical procedures in the treatment of breast cancer.
Cholesterol efflux from normal and Tangier disease fibroblasts into normal, high-density lipoprotein-deficient, and apolipoprotein E-deficient plasmas
Authors: S. Schuler-Lüttmann, Y. Zhu, M. Hoffmann, W. März, G. Feussner, H. Wieland, G. Assmann, A. von Eckardstein
Journal: Metabolism (2000)
The mitochondriotoxic domain of Vpr determines HIV-1 virulence
Authors: Catherine Brenner, Guido Kroemer
Journal: Journal of Clinical Investigation (2003)

Most patients infected with HIV-1 develop AIDS unless they receive antiretroviral medication. However, a small number of HIV-infected individuals with high viral titers remain disease free and do not experience progressive immunosuppression, even in the absence of therapy. Such individuals are labeled long-term nonprogressors (LTNPs) and are characterized by a series of laboratory parameters that are usually compromised in HIV-1 carriers who ultimately develop AIDS. In particular, LTNPs possess a high frequency of peripheral CD4plus; T cells, as well as a low level of spontaneous apoptosis, correlating with a normal mitochondrial transmembrane potential (Δψm) among circulating T cells. It has long been assumed that, as an experimentum naturae, LTNPs might furnish valuable clues for the identification of molecular determinants of HIV-1 pathogenesis. A study by Badley and colleagues involving LTNPs, reported in this issue of the JCI (1), strongly suggests that viral protein R (Vpr) is a major HIV-1 virulence factor.
Native American Ancestry Affects the Risk for Gene Methylation in the Lungs of Hispanic Smokers from New Mexico
Authors: Shuguang Leng, Yushi Liu, Cynthia L. Thomas, W. James Gauderman, Maria A. Picchi, Shannon E. Bruse, Xiequn Zhang, Kristina G. Flores, David Van Den Berg, Christine A. Stidley, Frank D. Gilliland, Steven A. Belinsky
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Gene promoter methylation detected in sputum predicts lung cancer risk in smokers. Compared with non-Hispanic whites (NHW), Hispanics have a lower age-standardized incidence for lung cancer.This study compared the methylation prevalence in sputum of NHWs with Hispanics using the Lovelace Smokers cohort (n = 1998) and evaluated the effect of Native American ancestry (NAA) and diet on biomarkers for lung cancer risk.Genetic ancestry was estimated using 48 ancestry markers. Diet was assessed by the Harvard University Dietary Assessment questionnaire. Methylation of 12 genes was measured in sputum using methylation-specific polymerase chain reaction. The association between NAA and risk for methylation was assessed using generalized estimating equations. The ethnic difference in the association between pack-years and risk for lung cancer was assessed in the New Mexico lung cancer study.Overall Hispanics had a significantly increased risk for methylation across the 12 genes analyzed (odds ratio, 1.18; P = 0.007). However, the risk was reduced by 32% (P = 0.032) in Hispanics with high versus low NAA. In the New Mexico lung cancer study, Hispanic non-small cell lung cancer cases have significantly lower pack-years than NHW counterparts (P = 0.007). Furthermore, compared with NHW smokers, Hispanic smokers had a more rapidly increasing risk for lung cancer as a function of pack-years (P = 0.058).NAA may be an important risk modifier for methylation in Hispanic smokers. Smoking intensity may have a greater impact on risk for lung cancer in Hispanics compared with NHWs.
Continuing medical education for the rheumatologist.
Authors: D P Symmons
Journal: Annals of the Rheumatic Diseases (1991)

It was his sixth interview but he has finally made it-a single-handed consultant in a district general hospital.His nearest rheumatological colleague will be 30 miles away.It has taken 18 years of training since he left school to reach his desired goal.He has taken numerous examinations and written a learned thesis.His sense of achievement is great.He is also apprehensive.Johnie is aware that his non-rheumatological colleagues and junior staff will look to him for definitive pronouncements on the latest treatment for polyarteritis nodosa, current theories on the cause of rheumatoid arthritis, and whether non-steroidal anti-inflammatory creams are efficacious.His patients will expect him to use the most modem diagnostic techniques and treatments.None of his previous education seems to have equipped him for this task of keeping up to date.How will he cope?Johnie is fictitious, but his dilemma is real.Every consultant rheumatologist needs to con- tinue to acquire and implement new knowledge throughout his working career.Many feel themselves to be poorly equipped for this task of continuing medical education.Medical education has three phases.The first
Law and medicine. Misdiagnosis of pregnancy
Authors: A. R. Holder
Journal: JAMA (1971)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Venereal Infections in Children
Authors: Charles Q. McClelland
Journal: JAMA (1979)

To the Editor.—  We are replying to the thoughtful article by James et al entitled Physician Reporting of Sexual Abuse of Children appearing inThe Journal(240:1145, 1978). This article effectively identified a major problem present in all areas of the country, ie, the failure of private physicians to identify and report appropriately instances of  abuse of children. However, we think that there may have been one omission in the original study design. Currently, the term sexual  is a broader one that relates not only to issues of rape,  assault, and molestation or incest but also identifies those patients with evidence of venereal infection in the pharynx, vagina, or rectum resulting from any form of legally and morally prohibited  experience.  The failure of this study to concern itself with the equally important problem of venereal infection as the result of  misuse in the child population
Looking and Doing A Method of Creative Therapy with Neurotic Patients
Authors: Hijmans van den Bergh
Journal: Psychotherapy and Psychosomatics (1971)

Two major viewpoints, a) In creative therapy (CT), we should focus more on therapy and less on diagnosis, therapist hobbies and general theories, b) It is possible to apply the craft of intensive psychotherapy to CT. – Conditions for this to come about: consistent thinking and consistent organisation. Framework of the article. After paragraphs on diagnostic aims in CT (tenet: diagnosis does not work that way) and on research, the author distinguishes various therapeutic aims in CT and various modes of its use. Their structural characteristics are defined. Then, using CT in 'De Viersprong' as an example, the author discusses such particular requirements and opportunities as are offered by the psychotherapy of neurotics and by residential treatment.
FcRn: an IgG receptor on phagocytes with a novel role in phagocytosis
Authors: Gestur Vidarsson, Annette M. Stemerding, Nigel M. Stapleton, Suzanne E. Spliethoff, Hans Janssen, Frank E. Rebers, Masja de Haas, Jan G. van de Winkel
Journal: Blood (2006)
FBI arrests doctor wanted in Australia
Authors: Bob Burton
Journal: BMJ (2008)

Jayant Patel, a surgeon sought by the police in Queensland over allegations concerning his medical registration and his performance at a hospital in the state, has been arrested in Oregon by the Federal Bureau of Investigation.

Dr Pateloperated on about 1000 patients while he was at Bundaberg Base Hospital between April 2003 and April 2005. Australian authorities want Dr Patel extradited from the United States to face 16 charges, including three of manslaughter, two of causing injuries, and seven counts of fraud. US Department of Justice documents filed with the District Court for Oregon state that Dr Patel “faces up to two life terms plus …
Stages of Salt Exchange in Essential Hypertension
Authors: D. M. GREEN, A. D. JOHNSON, W. C. BRIDGES, J. H. LEHMANN
Journal: Circulation (1954)

The relation of sodium to hypertension remains one of the most fascinating problems in medicine. The results accumulated over a five-year period of study of this relationship are presented in the paper which follows. In these investigations the appetite for salt and the output of sodium under a variety of loading conditions have been correlated with cardiac and renal function and compared with the patterns found in experimental corticoid and renal hypertensions.
BMJ is in danger of losing sight of the patient
Authors: M. Hewitt
Journal: BMJ (2011)

Amid the controversy surrounding the 1998 Lancet paper is a group of autistic children and young adults who for the past 20 years have had bowel problems.1 Whether their problems are seen as constipation or inflammation, these patients endure ongoing pain and discomfort, which exacerbates their already fragile condition.

Anecdotally (without research into …
Abstract LB-224: Development of a novel breast cancer segregation panel assay for multiple genetic subtyping based on gene expression modules developed from Oncomine™
Authors: Kahuku Oades, Sukla Chattopadhyay, Hyunsoo Kim, Lien Vo, David Telford, Yipeng Wang, Byung-in Lee, Joseph Monforte, Gordon Vansant, John Freshley, Peter Wyngaard, Daniel Rhodes, Scott Tomlins
Journal: Cancer Research (2011)

Abstract Breast cancer is a highly heterogeneous disease as evidenced by comprehensive genetic studies which have revealed multiple subtypes using gene expression profiling and cell lineage classifier analyses. Previous studies have characterized different subtypes including normal breast-like, luminal epithelial A, luminal epithelial B, Her 2 over-expression and basal type carcinoma. However, the genetic variation within breast cancer is far more diverse than these core subtypes, and it is necessary to fully characterize this diversity in order to move beyond simple prognosis and to specifically predict drug sensitivity. In a review of global gene expression and SNP-based cytogenetic data of more than 5,000 breast cancer patients in the Oncomine™ database, we have been able to characterize approximately 30 different genetic variations that are shared by 1% or more of the breast cancer population. These core, independent variables reflect diverse elements of the disease at a molecular level including cell lineage, dysregulated core biological functions, factors of cell growth, and importantly, the tumor microenvironment. Further genetic subtypes are characterized within the various large and focal genomic amplifications, such as Her2 and Myc, as well as focal expression events present subpopulations of patients. In aggregate these genetic variables represent all of the major genetic factors that present within breast cancer. Currently biomarker/diagnostic approaches have tended to be over-tailored to specific clinical questions and therefore have lacked broad applicability, with every diagnostic test requiring a custom gene set and tailored signature and in some cases, requiring separate validated assays using multiple technologies and consequent splitting of clinical samples. To overcome these limitations, we have developed a single, 96-gene qRT-PCR test for rapid breast cancer companion diagnostics development using FFPE tumor tissue. All 30 of the core variables or “modules” are represented by this test which reports on both gene expression and chromosomal amplification events. We demonstrate in this study that this single test, with its multiple modules, can report on standard histopathological parameters, such as ER, PR and Her2, and reproduce existing prognostic and predictive genomic signatures. Data will be presented on prediction of overall survival, neoadjuvant chemotherapy response, and in-vitro sensitivity to MEK and PI3K inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-224. doi:10.1158/1538-7445.AM2011-LB-224
Dopamine inhibits renal Na+:HCO3- cotransporter in rabbits and normotensive rats but not in spontaneously hypertensive rats
Authors: Motoei Kunimi, George Seki, Chiaki Hara, Shigeo Taniguchi, Shu Uwatoko, Astuo Goto, Satoshi Kimura, Toshiro Fujita
Journal: Kidney International (2000)
Letter: Incidence of postpartum deep vein thrombosis in the tropics.
Authors: T Chumnijarakij
Journal: BMJ (1974)

which suggests a low incidence of this phenomenon in Vietnam.Since the incidence of postpartum thromboembolic complications in Thailand is also supposed to be rare, 41,056 clinical charts from the Chulalongkorn Hospital for the years 1970- 71 were analysed retrospectively to determine the occurrence of postpartum thromboembolism (see table ).The prevalence of postpartum thrombo- embolic complication was 1-7 per 10,000 deliveries.The results of a similar study at on 22 July
Ultrastructural mapping of methyldopa and anti-D IgG erythrocyte antigen receptors.
Authors: S P Masouredis, E Sudora
Journal: Journal of Clinical Investigation (1975)

The ultrastructural distribution pattern and site density of alpha-methyldopa immunoglobin G (alpha-MD IgG) on the red cell membrane was observed and compared with that of anti-D IgG, with ferritin-conjugated rabbit anti-human IgG and [125I]anti-D. alpha-MD IgG binds to all common types of human red cells, both Rho (D) positive and negative, to give a random, aperiodic distribution pattern grossly indistinguishable from the red cell D receptor site pattern. alpha-MD IgG inhibits the binding of [125I]anti-D to D-positive red cells when the reaction is controlled with respect to total reaction volume, ionic strength, and the appropriate concentrations of the two IgG reactants. To determine if a alpha-MD IgG binds to the D-antigen receptor, D-positive red cells were sensitized with alpha-MD and [125I]anti-D IgG spearately and with both IgG preparations. The cell-bound radioactivity served to identify what proportion of the total ferritin-labeled IgG sites were due to anti-D. With nonsaturating concentrations of anti-D the number of IgG sites observed was equal to the sum of the sites found when the red cell was sensitized separately with alpha-MD and anti-D IgG. With saturating concentrations of anti-D there was a reduction in the expected number of IgG sites, indicating that alpha-MD IgG was excluded from binding. There was no comparable interaction of alpha-MD IgG and anti-D IgG when D-negative red cells were used. The results obtained indicate that alpha-MD IgG does not bind to the D antigen. The interaction between alpha-MD IgG and anti-D IgG for binding sites on the red cell membrane may be due to the close physical proximity of the two receptors, so as to produce steric hindrance in binding of the two IgG preparations when both are present. The alpha-MD IgG receptor appears to be a part of the Rh antigen complex that occurs in both D-positive and D-negative red cells and probably contains receptors for other types of warm-antibody immune hemolytic anemias.
World has been slow to act on polio outbreak in Syria, charity warns
Authors: A. Gulland
Journal: BMJ (2014)

Aid agencies and health organisations must learn lessons from the polio outbreak in Syria to ensure that a similar crisis does not occur in other warring nations, an epidemiologist working for the charity Save the Children has said.

Francesco Checchi, senior humanitarian health adviser at the charity, was speaking at a London meeting of the Royal Society of Medicine about the crisis in Syria. He said that the world had been slow to act when the warning signs of a potential polio outbreak were apparent before the first cases were reported.

He said that routine vaccination had stopped almost as soon as the conflict began three years ago and that many Syrians had been living in ideal …
What Constitutes an Expert Witness?
Authors: Charles Marwick
Journal: JAMA (1993)

SEEKING to keep "junk science" from influencing deliberations on a variety of vital matters in the nation's courtrooms, the American Medical Association (AMA) and its journal,<i>JAMA</i>, have each joined with several other scientific groups in filing amicus curiae briefs as the US Supreme Court considers the case of<i>Daubert v Merrell Dow Pharmaceuticals Inc</i>. When is expert scientific testimony to be allowed in court to be heard and weighed by a jury? When and on what grounds is it to be ruled out? For the first time, the Court will try to define the criteria judges should use to decide on admitting testimony by expert witnesses. The case that led the Court to agree to attempt to resolve the issue came up for argument last month. The plaintiffs allege that the antinausea drug Bendectin is a teratogen that causes limb reduction defects. Action was brought against its manufacturers, now
Audrey Irene Freeth
Authors: Derek Freeth
Journal: BMJ (2004)

Former consultant obstetrician and gynaecologist Western Hospital, Glasgow, and Vale of Leven (b London 1913; q Royal Free Hospital, London, 1937; FRCOG), died from bronchopneumonia and cerebrovascular disease on 20 August 2004.

At the Royal Free Hospital she won the Gant gold medal in surgery and the obstetrics prize, and was awarded the Hornblower-Cock scholarship in medicine to tour the United States. During the second world war she was resident surgical officer at the Birmingham Maternity Hospital, which included training demobilised medical officers for consultant posts. She retired to Auchencairn, Kirkcudbrightshire, where she founded the Minnoch Charitable Trust.
Advances in targeted therapies VIII
Authors: F C Breedveld, J R Kalden, J S Smolen
Journal: Annals of the Rheumatic Diseases (2006)

The papers brought together in this supplement of the Annals of the Rheumatic Diseases constitute summaries of presentations at the Eighth International Symposium on Advances in Targeted Therapies, which was held on 5–9 April 2006. As such these presentations represent the state of the art on the biology of mechanisms of action and pathophysiology of tumour necrosis factor (TNF) as well as other important mediators of inflammation. Current knowledge on the means and consequences of blocking TNF or other molecules or cellular mechanisms is presented as well.

We are grateful to Drs Crofford, Furst, Feldmann, Klareskog, …