tbuckley/cabot-search huggingface dataset:
French healthcare system beset by strikes
Authors: A. Dorozynski
Journal: BMJ (2002)

Sporadic strikes and demonstrations by doctors and other health staff in France during the past two months peaked last Wednesday with a “no doctor” day, during which hospitals and emergency wards were overwhelmed by calls from patients whose doctors had switched their telephone to an answering service.

More than 10 000 nurses demonstrated in Paris against low salaries and long hours. Negotiations between medical unions and government and health insurance officials over the weekend led to only partial agreement on minor increments in doctors' fees. More strikes and demonstrations are expected in the …
Abstract 2405: Loss of TBK1 induces an epithelial-mesenchymal transition through upregulation of Slug in the breast cancer cell lines
Authors: Kyung-Min Yang, WonJoo Kim, YunShin Jung, Seong-Jin Kim
Journal: Cancer Research (2012)

Abstract Estrogen receptor alpha (ER alpha) is a key regulator of proliferation and differentiation in mammary epithelium through their well-documented effects on transcription and represents a crucial prognostic indicator and therapeutic target in breast cancer. Here, we show that loss of TBK1 in ER alpha positive breast cancer cells causes an epithelial-mesenchymal transition (EMT). We found that TBK1 is downregulated in ER alpha negative breast tumors by analyzing published microarray data sets, suggesting that TBK1 might regulate ER alpha expression. To investigate this hypothesis, we made the ER alpha positive breast cancer cell lines stably expressing TBK1-specific shRNA. Knockdown of TBK1 decreased E-cadhrein expression (epithelial marker) and increased N-cadherin, vimentin, fibronectin expression (mesenchymal marker). Additionally, loss of TBK1 in ER alpha positive breast cancer cell lines leads to the downregulation of ER alpha expression. Interestingly, ER alpha repression by knockdown of TBK1 induced the upregulation of transcriptional repressor Slug, a master regulator of EMT. Because ER alpha expression is suppressed by loss of TBK1, it is suggested that TBK1 plays a role in the inverse correlation between Slug and ER alpha. Our findings indicate that loss of TBK1 expression is associated in between ER alpha expression status and invasive growth of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2405. doi:1538-7445.AM2012-2405
Use of cloned and expressed human liver UDP-glucuronosyltransferases for analysis of drug glucuronide formation and assessment of drug toxicity.
Authors: B Burchell, T Ebner, S Baird, S Bin Senafi, D Clarke, C Brierley, L Sutherland
Journal: Environmental Health Perspectives (1994)

Five cloned human hepatic UDP-glucuronosyltransferase (UGT) cDNAs were stably expressed in tissue culture cell lines. More than 100 drugs and xenobiotics were used as substrates for glucuronidation catalyzed by the cloned human transferases to determine the chemical structures accepted as substrates. UGT-HP1 exhibited a limited substrate specificity for planar phenolic compounds, whereas UGT-HP4 was more accepting of nonplanar phenols, anthraquinones, flavones, alphatic alcohols, aromatic carboxylic acids, steroids and many drugs of varied structure. UGT-HP3 (bilirubin UGT) catalyzed the glucuronidation of ethinylestradiol. UGT-H6 and UGT-H25 (steroid/bile acid UGTs) also catalyzed the glucuronidation of some xenobiotics. Levels of UGT-HP4 activity towards some substrates were sufficient to allow determination of kinetic parameters for the enzyme reaction. Further, metabolism of drugs could be studied by addition to the recombinant cell lines in culture and extraction of the media allowed analysis of glucuronide formation. The protection afforded against cytotoxic drugs was observed. The data presented here demonstrate the potential of using these recombinant cell lines for investigation of phase II metabolism by human UGTs and subtle differences in protein structure which affect their specificity.
Investigation into GPs with high patient mortality: Monitoring death rates will become increasingly complex
Authors: Julie Billett, Nick Kendall, Peter Old
Journal: BMJ (2004)

EDITOR—Like Mohammed et al, we investigated several general practitioners (GPs) who signalled as having “unacceptably” high death rates in the study undertaken by Aylin et al.1 2 We also concluded that these higher than expected death rates were explained by a “nursing home effect.”

Our methods included calculating standardised …
Symptoms of Disease in Childhood
Authors: W. J Bassett
Journal: BMJ (1995)

My initial enthusiasm for this book, which is intended as a teaching aid and a successor to Illingworth's classic Common Symptoms of Disease in Childhood, soon waned. Interactive, problem solving, and computer assisted techniques of medical teaching have not entirely displaced the need for textbooks, but to succeed these must have a visual impact and present information in a readable and enjoyable format. “What no pictures; no diagrams!” was the comment of one trainee to whom I showed it. He has a point; a good clinical photograph is worth a lot of words.

It is difficult to avoid the impression that …
A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation
Authors: Sorin V Fedeles, Xin Tian, Anna-Rachel Gallagher, Michihiro Mitobe, Saori Nishio, Seung Hun Lee, Yiqiang Cai, Lin Geng, Craig M Crews, Stefan Somlo
Journal: Nature Genetics (2011)
Making the new deal for junior doctors happen
Authors: S Dowling
Journal: BMJ (1994)

EDITOR, - Julie K Moore and colleagues' report of improvements in the preregistration year in the Wirral is encouraging.1 It contains two aspects that deserve greater emphasis as possible contributors to the process of change.

Firstly, medical students considering which jobs to apply for may not be as powerless as they sometimes feel. If these “consumers” of basic medical education vote with their feet (in this case only a third of posts could be filled) they provide compelling reasons why managers …
EXPERIMENTAL INFECTION OF THE CHICK EMBRYO WITH THE VIRUS OF PSEUDORABIES
Authors: Frederik B. Bang
Journal: The Journal of Experimental Medicine (1942)

The chick embryo responds to experimental infection with the virus of pseudorabies with a disease pattern simulating the natural infection. Virus lesions of the membrane are followed by infection of all tissues of the central nervous system. Fixed strains produce a hemorrhagic destruction of the central nervous system of the embryo, which is referable to destruction of blood vessel endothelium. Field strains lack the hemorrhagic tendency, but infect the brain when inoculated on the membrane. Neutralization of the virus by specific hyperimmune serum can be demonstrated by inoculation on the membrane. The reaction of the embryo to the virus varies with the age of the embryo. This is reflected both in the membranal lesion and in the subsequent encephalitis.
Incidence of IgA vasculitis in the adult Slovenian population
Authors: A. Hočevar, Z. Rotar, J. Ostrovršnik, V. Jurčić, A. Vizjak, M. Dolenc Voljč, J. Lindič, M. Tomšič
Journal: British Journal of Dermatology (2014)

IgA vasculitis (IgAV) is assumed to be uncommon in adults.To determine the incidence rate of histologically proven IgAV in the adult Slovenian population.A retrospective chart review of adult patients diagnosed with IgAV was performed at the departments of rheumatology, nephrology, infectious diseases and dermatovenereology at an integrated secondary/tertiary university teaching hospital. In order to avoid missing miscoded cases, the Institute of Pathology, University of Ljubljana, Slovenia, provided a list of all patients with an IgAV-compatible histological pattern on biopsy. The annual incidence rate of histologically proven IgAV was calculated.Eighty-one new cases of IgAV were identified from June 2010 to June 2013. The estimated annual incidence rate of IgAV was 5·1 per 100,000 adults [95% confidence interval (CI) 3·4-7·4]; in men it was 6·1 per 100,000 (95% CI 3·9-10·6) and in women it was 3·7 per 100,000 (95% CI 1·8-6·8).Although we only included histologically proven cases of IgAV, the annual incidence rate of 5·1 per 100,000 adults is 3-6-times higher than previously reported.
20-Year Trends in the Prevalence of Asthma and Chronic Airflow Obstruction in an HMO
Authors: WILLIAM M. VOLLMER, MOLLY L. OSBORNE, A. SONIA BUIST
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Although asthma is on the rise in the United States and elsewhere, data on age–sex-specific patterns of change in various types of health care utilization are scarce. We report on 20-yr trends in the treated prevalence of asthma among members of a large health maintenance organization. Data are presented separately for each of six age–sex categories, and include both the treated prevalence of asthma as well as the treated prevalence of the broader category of chronic airflow obstruction (CAO), defined as asthma, chronic bronchitis, or emphysema. During the period 1967–1987 the treated prevalence of asthma and CAO increased significantly in all age–sex categories except males aged 65 and older. These patterns are in contrast to previous studies of this population that showed that increases in asthma hospitalizations and hospital-based episodes of care were limited primarily to young boys. Not only do these findings support other evidence of a real increase in asthma prevalence, but they also highlight the risks associated with drawing inferences about changing disease epidemiology based on a single type of health care utilization.
IRREGULAR SURFACE AND INTRALUMINAL MATERIAL DETECTED BY OPTICAL COHERENCE TOMOGRAPHY IS USEFUL TO PREDICT DISTAL EMBOLISM AFTER CUTTING BALLOON ANGIOPLASTY FOR IN-STENT RESTENOSIS
Authors: Masayuki Taniike, Masami Nishino, Naotaka Okamoto, Akihiro Tanaka, Atsushi Kikuchi, Takeshi Masaki, Naoki Mori, Daisuke Nakamura, Takahiro Yoshimura, Yasuharu Lee, Nobuhiko Makino, Hiroyasu KATO, Yasuyuki Egami, Ryu Shutta, Hisaki Morita, Jun Tanouchi, Yoshio Yamada
Journal: Journal of the American College of Cardiology (2012)
Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder.
Authors: M R Freeman, J J Yoo, G Raab, S Soker, R M Adam, F X Schneck, A A Renshaw, M Klagsbrun, A Atala
Journal: Journal of Clinical Investigation (1997)

The epidermal growth factor receptor (HER1) has been implicated in regenerative growth and proliferative diseases of the human bladder epithelium (urothelium), however a cognate HER1 ligand that can act as a growth factor for normal human urothelial cells (HUC) has not been identified. Here we show that heparin-binding EGF-like growth factor (HB-EGF), an activating HER1 ligand, is an autocrine regulator of HUC growth. This conclusion is based on demonstration of HB-EGF synthesis and secretion by primary culture HUC, identification of HER1 as an activatable HB-EGF receptor on HUC surfaces, stimulation of HUC clonal growth by HB-EGF, inhibition of HB-EGF-stimulated growth by heparin and of log-phase growth by CRM 197, a specific inhibitor of HB-EGF/HER1 interaction, and identification of human urothelium as a site of HB-EGF precursor (proHB-EGF) synthesis in vivo. ProHB-EGF expression was also detected in the vascular and detrusor smooth muscle of the human bladder. These data suggest a physiologic role for HB-EGF in the regulation of urothelial proliferation and regeneration subsequent to mucosal injury. Expression of proHB-EGF is also a feature of differentiated vascular and detrusor smooth muscle in the bladder. Because proHB-EGF is known to be the high affinity diphtheria toxin (DT) receptor in human cells, synthesis of the HB-EGF precursor by human urothelium also suggests the possibility of using the DT-binding sites of proHB-EGF as an in vivo target for the intraluminal treatment of urothelial diseases.
Preclinical Evaluation of Gemcitabine Combination Regimens for Application in Acute Myeloid Leukemia
Authors: Ryan H. Shanks, David A. Rizzieri, James L. Flowers, O. Michael Colvin, David J. Adams
Journal: Clinical Cancer Research (2005)

Abstract The DNA antimetabolite gemcitabine is an anticancer agent with shown preclinical and clinical utility and a low toxicity profile. In this study, we sought to identify and optimize drug partners for binary and tertiary combinations with gemcitabine for use in the treatment of acute myelogenous leukemia (AML). Drug interaction was assessed by growth inhibition assay with metabolic end points. The combination index method was used to evaluate combinations of gemcitabine with fludarabine, paclitaxel, chlorambucil, doxorubicin, mitoxantrone, and SN-38 in U937 human AML cells. A three-dimensional method was used to determine the effect of dose ratio and schedule on drug interaction. Mechanisms underlying interactions related to cell cycle effects and apoptosis were assessed by flow cytometric and caspase-3 and -7 assays, respectively. The most synergistic binary combination was gemcitabine + fludarabine. The most synergistic tertiary combination was gemcitabine + fludarabine + paclitaxel, where the interaction was sequence dependent with paclitaxel given before gemcitabine + fludarabine, producing a 2-fold increase in synergy. Cell cycle analysis did not reveal a significant G2-M arrest, suggesting that the synergistic effect of paclitaxel in this combination, which produced the greatest caspase activation, might be independent of microtubule stabilization. In contrast, the gemcitabine + fludarabine + mitoxantrone combination was synergistic and schedule independent. Moreover, few ratios of gemcitabine + fludarabine to mitoxantrone were antagonistic, which could be important for clinical translation. In conclusion, synergistic interactions with gemcitabine occurred with several drugs, the most promising being gemcitabine + fludarabine, gemcitabine + fludarabine + paclitaxel, and gemcitabine + fludarabine + mitoxantrone. These findings provided a rationale for clinical trials of gemcitabine + fludarabine and gemcitabine + mitoxantrone where responses were observed in heavily pretreated AML patients.
After initial anticoagulation for a first unprovoked venous thromboembolism, aspirin reduced recurrence
Authors: Andrew Dunn
Journal: Annals of Internal Medicine (2015)

Source Citation Simes J, Becattini C, Agnelli G, et al; INSPIRE Study Investigators (International Collaboration of Aspirin Trials for Recurrent Venous Thromboembolism). Aspirin for the prevention of recurrent venous thromboembolism: The INSPIRE Collaboration. Circulation. 2014;130:1062-71. 25156992
High avidity IFN-neutralizing antibodies in pharmaceutically prepared human IgG.
Authors: C Ross, M Svenson, M B Hansen, G L Vejlsgaard, K Bendtzen
Journal: Journal of Clinical Investigation (1995)

This paper demonstrates and characterizes naturally occurring antibodies to interferon (IFN) in human IgG preparations. In vitro neutralization of the antiviral effect of IFN alpha and IFN beta, but not IFN gamma, was observed in 12 of 15 normal IgG preparations. The neutralizing capacity was higher against rIFN alpha 2A and rIFN alpha 2C than against lymphoblastoid IFN alpha and IFN beta. Frühsommer meningoencephalitis hyperimmune IgG and hepatitis-B hyperimmune IgG showed potent neutralization, whereas anti-rhesus D-, anti-rabies-, and anti-tetanus IgG showed weak neutralization. Saturable binding of 125I-rIFN alpha 2A was demonstrated only in those IgG preparations found to neutralize the antiviral effect of IFN. Significant correlation between IFN binding and neutralization capacity was observed. The antibodies bound with Fab to rIFN alpha 2A with an avidity of approximately 30 pM; the majority was of the IgG1 subclass. Maximum binding capacity was 490 pg rIFN alpha 2A/mg IgG. Cross-binding of rIFN alpha 2C, lyIFN alpha N1 and IFN beta occurred with 10 and 100-200 times lower activities than that of rIFN alpha 2A. There was no cross-binding with rIFN gamma or rIL-6. IgG preparations containing anti-IFN antibodies blocked the binding of 125I-rIFN alpha 2A to A549 cells. In conclusion, pharmaceutically prepared human IgG preparations contain variable but significant levels of high-avidity IFN alpha and IFN beta neutralizing antibodies.
Effects of prolonged ethanol intake and malnutrition on rat pancreas.
Authors: J M Lopez, J A Bombi, R Valderrama, A Gimenez, A Pares, J Caballeria, S Imperial, S Navarro
Journal: Gut (1996)

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.
Patients challenge decision to hold Mid-Staffordshire inquiry in private and restrict its scope
Authors: C. Dyer
Journal: BMJ (2009)

The Department of Health faces a High Court challenge over its decision to hold the inquiry into poor standards of care at Mid-Staffordshire NHS Foundation Trust in private.

Patients who allege that they were subjected to “appalling” standards of treatment, and relatives of those who died under the trust’s care, are applying for a judicial review of decisions to hear evidence in private and to limit the scope of the inquiry.

The local patients’ pressure group Cure the NHS wants the inquiry to go beyond the boundaries of the trust and look at the roles of …
Do All Leukemic Cells Have an Abnormal Karyotype?
Authors: Janet D. Rowley
Journal: New England Journal of Medicine (1981)

Over the past 20 years, analysis of the chromosome pattern in bone-marrow cells from patients with leukemia has resulted in a number of remarkable observations.1 The increase in our understanding of this pattern has been especially rapid in the past eight years, because various chromosome-banding techniques developed in the early 1970s have been used to study chromosomes from leukemic cells. These techniques permit precise identification of each human chromosome and of segments of these chromosomes. As a result, nonrandom patterns of chromosomal gains or losses have been identified in leukemic cells. Probably of greater biologic importance is the observation that . . .
Iron Therapy in Hemodialysis Patients: Time for a Reappraisal
Authors: Lee E. Human
Journal: JAMA (1980)

The inevitable anemia of long-term hemodialysis patients is frequently the chief factor that keeps them from feeling well and in many exaggerates their coronary artery disease, poor myocardial performance, and cerebral dysfunction. The urgency that the dialysis physician feels to boost his patient's RBC mass is understandable but usually frustrated. Frequent transfusions are expensive and may lead to hepatitis or siderosis. Androgen therapy can result in a modest rise in the hematocrit value, but the masculinizing side effects in women, the fear of hepatocellular tumors in patients with long life expectancies, and cost limit its value. Careful techniques to reduce blood loss accompanying each dialysis and routine dietary supplement with folate are already generally employed in most dialysis units. In the early days of hemodialysis, the unavoidable blood loss occurring with each treatment, the often poor dietary intake, and the use of phosphate-binding gels gave rise to the assumption that
Quantitation of isoprenaline-induced changes in the ventricular myocardium
Authors: P. COLLINS, C. G. BILLINGS, G. R. BARER, J. J. DALY, A. JOLLY
Journal: Cardiovascular Research (1975)

Journal Article Quantitation of isoprenaline-induced changes in the ventricular myocardium Get access P. COLLINS, P. COLLINS From the Department of Experimental Medicine, The Royal Hospital, West Street, Sheffield Search for other works by this author on: Oxford Academic PubMed Google Scholar C. G. BILLINGS, C. G. BILLINGS From the Department of Experimental Medicine, The Royal Hospital, West Street, Sheffield Search for other works by this author on: Oxford Academic PubMed Google Scholar G. R. BARER, G. R. BARER From the Department of Experimental Medicine, The Royal Hospital, West Street, Sheffield Search for other works by this author on: Oxford Academic PubMed Google Scholar J. J. DALY, J. J. DALY From the Department of Experimental Medicine, The Royal Hospital, West Street, Sheffield Search for other works by this author on: Oxford Academic PubMed Google Scholar A. JOLLY A. JOLLY From the Department of Experimental Medicine, The Royal Hospital, West Street, Sheffield Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 9, Issue 6, November 1975, Pages 797–806, https://doi.org/10.1093/cvr/9.6.797 Published: 01 November 1975
Rheumatoid Pericarditis
Authors: ALEJANDRO E. FRANCO
Journal: Annals of Internal Medicine (1972)

Seventeen patients with rheumatoid pericarditis, diagnosed clinically, are compared with 41 cases reported in the literature and with 85 control patients with rheumatoid arthritis but without pericarditis. Rheumatoid pericarditis occurred in patients with definite or classical rheumatoid arthritis. Rheumatoid factor, present in 93% of the patients tested, was statistically commoner than in the control group. Subcutaneous nodules were present in 47%. The presenting complaints were left-sided chest pain (59%) and symptoms of congestive heart failure (18%). A pericardial friction rub was detected in 65%. All patients had cardiomegaly, as seen by X ray, accompanied by pleural effusion in 65%. A low sugar concentration in the pericardial fluid, elevated lactic dehydrogenase and gamma globulin levels, and, probably, a low complement value indicate rheumatoid arthritis as the most probable cause of the effusion. Over one third of the pericarditis patients eventually required pericardiectomy or died of their disease.