tbuckley/cabot-search huggingface dataset:
Disruption of the histone acetyltransferase MYST4 leads to a Noonan syndrome–like phenotype and hyperactivated MAPK signaling in humans and mice
Authors: Michael Kraft, Ion Cristian Cirstea, Anne Kathrin Voss, Tim Thomas, Ina Goehring, Bilal N. Sheikh, Lavinia Gordon, Hamish Scott, Gordon K. Smyth, Mohammad Reza Ahmadian, Udo Trautmann, Martin Zenker, Marco Tartaglia, Arif Ekici, André Reis, Helmuth-Guenther Dörr, Anita Rauch, Christian Thomas Thiel
Journal: Journal of Clinical Investigation (2011)

Epigenetic regulation of gene expression, through covalent modification of histones, is a key process controlling growth and development. Accordingly, the transcription factors regulating these processes are important targets of genetic diseases. However, surprisingly little is known about the relationship between aberrant epigenetic states, the cellular process affected, and their phenotypic consequences. By chromosomal breakpoint mapping in a patient with a Noonan syndrome–like phenotype that encompassed short stature, blepharoptosis, and attention deficit hyperactivity disorder, we identified haploinsufficiency of the histone acetyltransferase gene MYST histone acetyltransferase (monocytic leukemia) 4 (MYST4), as the underlying cause of the phenotype. Using acetylation, whole genome expression, and ChIP studies in cells from the patient, cell lines in which MYST4 expression was knocked down using siRNA, and the Myst4 querkopf mouse, we found that H3 acetylation is important for neural, craniofacial, and skeletal morphogenesis, mainly through its ability to specifically regulating the MAPK signaling pathway. This finding further elucidates the complex role of histone modifications in mammalian development and adds what we believe to be a new mechanism to the pathogenic phenotypes resulting from misregulation of the RAS signaling pathway.
Observations with Radioactive Hydrogen (H <sup>3</sup> ) in Experimental Atherosclerosis
Authors: MAX W. BIGGS, DAVID KRITCHEVSKY
Journal: Circulation (1951)

Tritium has been used to study certain aspects of endogenous and exogenous cholesterol metabolism in normal and hypercholesterolemic rabbits. Special attention is given to turnover studies on aortic cholesterol. Labeled cholesterol has been used for feeding experiments and the subsequent rise of serum cholesterol specific activity has been investigated.
Finland leads 31 European countries in tackling child injuries with Greece last
Authors: Z. Kmietowicz
Journal: BMJ (2012)

National governments need to do more to prevent children injuring themselves and dying in the home from drowning, falls, burns and scalds, poisoning, and choking or strangulation, according to an assessment of child safety policies in 31 countries across Europe.

The Netherlands leads Europe with the lowest rate of deaths from injury among children and adolescents in 2010 or the most recent year available (4.99 deaths from injury per 100 000 children aged 0 to 19), followed by Sweden (5.02), the UK (6.01), and Germany (6.16).1

The worst performing country is Lithuania (23.91 deaths per 100 000), followed by Bulgaria (17.37), Romania (17.20) and Latvia (16.06). The report covers 27 EU member states plus Croatia, Iceland, Israel, and Norway.

“A child dies every hour of every day in the EU as a …
180 Inhibition of nuclear factor-κB and phosphatidylinositol 3-kinase/AKT is essential for massive hepatocyte apoptosis induced by tumor necrosis factor α in mice
Authors: M IMOSE, M NAGAKI, T NAIKI, Y OSAWA, D BRENNER, T ASANO, H HAYASHI, M IMAO, S TAKAI, K KIMURA
Journal: Hepatology (2003)

Conditional deletion of the mouse Forkhead Box (Fox) m1b targeted allele in adult hepatocytes (Foxm1, previously called HFH-11B, Trident, Win, or MPP2) demonstrated that the Foxm1b transcription factor is essential for hepatocyte mitosis during liver regeneration. To determine the role of Foxm1b in liver development, we have generated Foxm1b −/− mice that deleted the Foxm1b exons encoding the winged helix DNA binding and transcriptional activation domains. Here, we show that all of the Foxm1b −/− embryos died in utero by 18.5 days postcoitum (dpc). Embryonic Foxm1b −/− livers displayed a 75% reduction in the number of hepatoblasts, resulting from diminished DNA replication and a failure to enter mitosis causing a polyploid phenotype. Reduced hepatoblast mitosis was associated with decreased protein levels of the Polo-like kinase 1 and Aurora B kinase, which phosphorylate regulatory proteins essential for orchestrating mitosis and cytokinesis. Diminished proliferation of Foxm1b −/− hepatoblasts contributed to abnormal liver development with significant reduction in the number of large hepatic veins compared to embryonic wild-type (WT) liver. Furthermore, embryonic Foxm1b −/− livers did not develop intrahepatic bile ducts, and these presumptive biliary hepatoblasts failed to express either biliary cytokeratins or nuclear levels of hepatocyte nuclear factor 1β. These results suggest that Foxm1b is critical for hepatoblast precursor cells to differentiate toward biliary epithelial cell lineage. Finally, we used a hepatoblast-specific Cre recombinase transgene to mediate deletion of the Foxm1b fl/fl allele in the developing liver, and these embryos died in utero and exhibited diminished hepatoblast proliferation with similar abnormalities in liver morphogenesis, suggesting that the defect in liver development contributed to embryonic lethality.
EFFECT OF STENT BOOST IMAGING GUIDED PERCUTANEOUS CORONARY INTERVENTION ON MID-TERM ANGIOGRAPHIC AND CLINICAL OUTCOMES
Authors: Cheol Ung Choi, Dong Joo Oh, Sureshkumar Ramasamy, Kanhaiya L. Poddar, Yun Kyung Kim, Jin Oh Na, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Seung-Woon Rha, Chang Gyu Park, Hong Seog Seo
Journal: Journal of the American College of Cardiology (2011)
Idiopathic Orthostatic Hypotension
Authors: Irwin J. Schatz
Journal: JAMA (1963)

The records of 29 patients with chronic idiopathic orthostatic hypotension (IOH) were reviewed and compared with records of 11 patients with a similar syndrome who had diabetes mellitus. Fifteen patients with IOH had significant central nervous system findings consisting of extrapyramidal defects, paresthesia, sphincter disturbances, pyramidal tract signs, and impotence, confirming the presence of a degenerative neurological disease in these patients. Diagnosis was made when there was the simultaneous occurrence of dizziness and syncope with a decline in standing blood pressure of 30/20 mm Hg. Treatment consisted of the use of physical measures to increase venous return, and the administration of vasopressor agents such as ephedrine. When such therapy was ineffective, fludrocortisone acetate was used and resulted in marked improvement in five patients.
Cell division in the synovial lining in experimental allergic arthritis: proliferation of cells during the development of chronic arthritis.
Authors: B Henderson, L E Glynn, J Chayen
Journal: Annals of the Rheumatic Diseases (1982)

The synovial tissue in experimentally induced immune arthritis induced in the rabbit has been used as a model of rheumatoid arthritis to determine which cells may contribute to the growth of this tissue. Tissue from the challenged and from the unchallenged knee joints was taken, after the intra-articular injection of a small amount of tritiated thymidine, from rabbits up to 3 months after the arthritis was induced. DNA synthesis, as a measure of cell proliferative activity, was assessed firstly by measuring the labelling index in autoradiographs of sections of such tissue, and secondly by the DNA synthetic index obtained by Feulgen cytophotometry. These measurements were made separately on synoviocytes, on the structural cells of the stroma, on the cells lining the small blood vessels, and on the infiltrating inflammatory cells. The DNA synthetic activity of the synoviocytes, and of the stromal noninflammatory cells, was maximal between 3 and 7 days after challenge. The activity in the synoviocytes, in particular, remained raised for up to 84 days after the challenge. Thus these cells appear to be capable of contributing to the hyperplasia, but the contribution of other cells, deeper in the stroma, cannot be excluded.
Impaired Kidney Function Associated with Both Syntax Score and Aortic Distensibility in Patients with Stable Coronary Artery Disease
Authors: Hakan Uçar, Mustafa Gür, Taner Şeker, Durmuş Yıldıray Şahin, Gökhan Gözübüyük, Caner Türkoğlu, Arafat Yıldırım, Onur Kaypaklı, Zafer Elbasan, Murat Çaylı
Journal: Journal of the American College of Cardiology (2013)
Great expectations: a relative dilemma
Authors: T. Cawood
Journal: BMJ (2001)

As a busy ward doctor I was finding it increasingly difficult to perform my clinical duties while also satisfying the multiple requests to speak to patients' relatives. At visiting time I walked faster than usual down the ward, eyes fixed firmly on the floor. Talking to relatives is an important part of the delivery of good patient care, but it takes time. Not only does it disrupt already tight working patterns, but also it often requires care, experience, and sensitivity. It is not easy to conduct an emotionally demanding interview, while respecting the patient's rights to confidentiality and addressing relatives' questions, fears, and anger.

> The ward could not safely function if the doctor spent 90 minutes a day talking to relatives 

Doctors spend an important amount of their time talking to patients' relatives. In an increasingly demanding NHS good communication has never been so crucial. The time spent talking to patients' relatives is time not spent attending to the other demands placed upon hospital staff. Improved communication should …
Matrix Metalloproteinases Play an Active Role in Wnt1-Induced Mammary Tumorigenesis
Authors: Laurence Blavier, Alisa Lazaryev, Frederick Dorey, Gregory M. Shackleford, Yves A. DeClerck
Journal: Cancer Research (2006)

The Wnt signaling transduction pathway plays a critical role in the pathogenesis of several murine and human epithelial cancers. Here, we have used mouse mammary tumor virus (MMTV)-Wnt1 transgenic mice, which develop spontaneous mammary adenocarcinoma, to examine whether matrix metalloproteinases (MMPs)--a family of extracellular proteases implicated in multiple steps of cancer progression--contributed to Wnt1-induced tumorigenesis. An analysis of the expression of several MMPs by RT-PCR and in situ hybridization revealed an increase in the expression of MMP-2, MMP-3, MMP-9, MMP-13, and MT1-MMP (MMP-14) in hyperplastic glands and in mammary tumors of MMTV-Wnt1 transgenic mice. Interestingly, whereas MMP-2, MMP-3, and MMP-9 were exclusively expressed by stromal cells in mammary tumors, MMP-13 and MT1-MMP were expressed by transformed epithelial cells in addition to the tumor stroma. To determine whether these MMPs contributed to tumorigenesis, MMTV-Wnt1 mice were crossed with transgenic mice overexpressing tissue inhibitor of metalloproteinase-2-a natural MMP inhibitor-in the mammary gland. In the double MMTV-Wnt1/tissue inhibitor of metalloproteinases-2 transgenic mice, we observed an increase in tumor latency and a 26.3% reduction in tumor formation. Furthermore, these tumors grew at a slower rate, exhibited an 18% decrease in proliferative rate, and a 12.2% increase in apoptotic rate of the tumor cells in association with a deficit in angiogenesis when compared with tumors from MMTV-Wnt1 mice. Thus, for the first time, the data provides evidence for the active role of MMPs in Wnt1-induced mammary tumorigenesis.
Academia's Chilly Climate for Primary Care
Authors: Susan D. Block
Journal: JAMA (1996)

<h3>Objective.</h3> —To describe the attitudes toward and perceptions of primary care education and practice among academic health center constituents. <h3>Design and Participants.</h3> —Descriptive study using confidential telephone interviews (October 1993 to March 1994) of national stratified probability samples of first- and fourth-year medical students, residents, clinical faculty, internal medicine and pediatrics residency training directors and chairs, and deans (N=2293). <h3>Results.</h3> —Five areas were examined: respondents' specialty orientation, attitudes toward the competence of primary care physicians, encouragement and positive regard for primary care, exposure to primary care-related educational experiences, and socioemotional orientation. The response rate was 84%. Respondents generally perceive primary care tasks as not requiring high levels of expertise; nearly half believe that generalists are not the best physicians to manage patients with serious illness and that the quality of primary care research is inferior to that in other fields. Attitudes are more positive toward the quality of primary care teaching. Learners perceive little encouragement for generalist careers and negative attitudes toward generalists among faculty, and view the quality of their primary care training as inferior to that for specialty practice. Those who have progressed further in the academic medicine hierarchy generally report lower levels of socioemotional orientation than individuals at earlier phases of career development. <h3>Conclusions.</h3> —Despite changes in the health care system and in education, students and residents encounter an atmosphere that is chilly toward primary care. If medical educators seek to optimize enthusiasm and preparation for primary care careers, they must develop approaches to changing the attitudes, values, and composition of their faculties.
Abstract 2918: Combining large scale biochemical and cellular profiling data to better understand the mechanism of anti-tumor drugs
Authors: Sharon Nauman, Jacob Bode, Clare Hadden, Lynn Byers, Blaine N. Armbruster
Journal: Cancer Research (2011)

Abstract This study was designed to elucidate the selectivity and cellular behavior of several marketed kinase inhibitors used in the treatment of cancer patients. Generally, kinase inhibitors are optimized to inhibit a single cellular target associated with cancer progression. However, most currently marketed kinase inhibitors interact with a highly conserved ATP binding site raising the question of their selectivity and therapeutic mechanism of action. Through EMD-Millipore's KinaseProfiler(TM) service, we functionally profiled the selectivity of Imatinib, Sunitinib, Lapatinib as well as several other marketed kinase inhibitors against a panel of over 250 kinases. Having identified the in vitro targets for these inhibitors, we next examined the potential of these small molecules to either directly inhibit several of the identified targets, or indirectly inhibit the activation of key signaling molecules downstream of these targets in several cell lines using EMD-Millipore's SignalProfiler(TM) service. Kinase profiling studies revealed that no kinase inhibitor was selective for a single target, with most inhibitors interacting with ten or more (sometimes phylogenetically distinct kinases) when tested at 1 µM. Additionally, several inhibitors were also found to either inhibit or activate certain GPCRs. The polypharmacology of the kinase inhibitors found through these studies would suggest that interaction with several molecular targets could contribute to either the therapeutic or adverse effects associated with these drugs. Current studies are underway to evaluate the cellular effect of these compounds to 1) resolve whether the compounds’ potential promiscuity, as revealed via biochemical studies, translates to a cellular context and 2) to assess whether drugs that share key therapeutic targets differentially affect cell signaling, due to differences in their off-target interactions. 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 2918. doi:10.1158/1538-7445.AM2011-2918
The Downsizing of Internal Medicine Residency Programs
Authors: David A. Asch, Jack Ende
Journal: Annals of Internal Medicine (1992)

▪ A variety of forces are converging to reduce the number of internal medicine residency positions offered in this country. This reduction, referred to as downsizing, has been proposed as the solution to several of the problems facing internal medicine. We examine the forces that underlie the current enthusiasm for downsizing; we consider the alternative strategies by which downsizing might be implemented; and we consider the implications of these alternatives on different groups of stakeholders. Although downsizing may represent a legitimate approach to real problems, any mechanism to reduce the number of training positions in internal medicine will have broad implications for medical education and patient care well into the next century. Special efforts must be taken to ensure that downsizing will not exacerbate the existing problems of overspecialization and limited access to care.
The New Surrogates for Board Certification — What Should the Standards Be?
Authors: Jerome P. Kassirer
Journal: New England Journal of Medicine (1997)

In this era of physician accountability, many organizations are searching for ways to evaluate physicians' performance. The principal method of the past — namely, the requirement of graduation from a training program and subsequent time-unlimited state licensure — seems naive in the context of the recent enthusiasm for assessing actual performance. Given that modern organizations, especially managed-care plans, still have little more than these criteria to go on when hiring new physicians, many use certification by 1 of the 24 member boards of the American Board of Medical Specialties (ABMS) as a major criterion for hiring.13 In fact, many . . .
Computerised information retrieval services in a teaching hospital.
Authors: J Welch
Journal: BMJ (1980)

The Wessex Medical Library of the University of Southampton is one of an increasing number of institutions that now provide online information retrieval for its medical, research, and teaching staff.The British Library Automated Information Service (BLAISE) is not the only system that provides medical publication citations online, but my aim is merely to give medical and paramedical readers an overview of today's facilities and a glimpse of tomorrow's potential. Plugging in for informationIn common with numerous other institutions of learning or research, computerised information retrieval services have been in operation at this library since the UK MEDLARS system- supplied by BLAISE-became available in Britain in April 1977.Availability at that time was the culmination of a two-year experiment that used a few online operators, sponsored by the British Library Lending Division in conjunction with the National Library of Medicine in Washington-where the MEDLARS files had originated as long ago as 1963.MEDLARS iS, of course, the online application of Index Medicus, the use of which has been described and illustrated in a tape-slide programme.'Anyone who remembers the old MEDLARS I batched retrieval system-when response time could be from two weeks to two months, with results which were often un- satisfactory anyway-would be contemptuous of it today, though we thought it pretty advanced at the time.Those concerned in this experiment were accessing the MEDLARS files at Elhill via satellite, which would have been cripplingly expensive for us had we been paying.As soon as the National Library of Medicine MEDLARS data bases were mounted at Harlow, Essex (on an IBM 370 series computer), the trans- atlantic link became unnecessary and BLAISE was born.The Elhill 3C package which made up the BLAISE programs had been developed by the National Library of Medicine over 15 years and, as a result, the system was trouble-free and has remained so.
Women in Sports
Authors: Joseph S. Torg
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The article on female athletics (228:1266, 1974) represents the position of the Committee on the Medical Aspects of Sports. It certainly marks a step forward. Although somewhat ambiguous, it helps dispel long-standing misconceptions regarding the physical capabilities of the female athlete, specifically, that there is no medical reason to exclude females from participating in contact sports with members of their own sex or, with the exception of football and ice hockey, with males of comparable physical abilities. I would like to point to what I believe to be three shortcomings of this communication. Although I fully agree with the concept that parallelathletic programs should be fostered and developed, it is questionable whether the Committee on the Medical Aspects of Sports should take a policy stand on matters that are not medically related and that are the responsibility of physical educators. Second, the Committee did not deal
THE EFFECT OF LDLR–NEGATIVE GENOTYPE ON AORTIC VALVE CALCIFICATION USING CARDIAC CT IN ASYMPTOMATIC STATIN TREATED PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
Authors: Admir Dedic, Gert–Jan ten Kate, Lisan Neefjes, Koen Nieman, Gabriel Krestin, Eric Sijbrands, Pim de Feyter, MC Erasmus
Journal: Journal of the American College of Cardiology (2013)
BMA meeting: BMA condemns government's "responsibility deals" with food and drinks industry
Authors: N. Hawkes
Journal: BMJ (2011)

Food and drink companies should not be involved in developing public health policy because they cannot be trusted, the BMA’s annual conference resolved today.

In an attack on the coalition government’s “responsibility deals” that bring together public, private, academic, and non-governmental experts in networks to tackle public health issues, delegates passed a motion declaring this would not provide “strong, effective, and evidence based” policy.

“Companies that are heavily involved have a lot to lose by taking a robust line,” argued …
Endoscopic ultrasound-guided fine needle aspiration training: evaluation of a new porcine lymphadenopathy model for in vivo hands-on teaching and training, and review of the literature
Authors: A. Fritscher-Ravens, T. Cuming, S. Dhar, S. Parupudi, K. Patel, A. Ghanbari, C. Holland, K. Hadeler, A. Arlt, M. Ellrichmann
Journal: Endoscopy (2013)

<b>Background and study aims:</b> Adequate training is required to achieve successful endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS – FNA). Of the variety of training models currently available, none offers verisimilitude to the tactile feel of puncturing a human lymph node. The aim of the current study was to evaluate a new porcine lymph node model for EUS – FNA training and to evaluate its impact on trainees' performance in patients compared with the literature of other models available. <b>Methods</b>: Two trainees each performed EUS – FNA of 96 lymph nodes in 18 animals with induced lymphadenopathy (mean 1.6 cm [range 0.9 – 3.5 cm]). Accuracy, speed, adequacy of sampling, and trainees' performance pre- and post-training were measured. Using a questionnaire, data were gathered regarding the effect of training and comfort level in patients. Results were compared with those in the literature. <b>Results:</b> Trainees progressed from hands-on assistance to occasional verbal guidance toward the end of animal training. There was good correlation between puncture time and number of EUS – FNA procedures performed in all but the subcarinal location (r = – 0.17). Comparison of trainee performance in patients before and after training showed a reduction in puncture time (<i>P </i> = 0.0014). Questionnaire analysis revealed increased confidence in echoendoscope- and needle-handling. Comparison with other published models supports these results. <b>Conclusion:</b> Results from the literature and the current study showed that animal training improves trainee performance, confidence, and procedural comfort when returning to patient examinations. The new model produces a realistic response that is similar to EUS – FNA in patients; this experience provides a benefit to endoscopists in terms of improved performance in patients and could be considered for use in accreditation. Due to the small numbers of trainees, larger experiences are needed to confirm training efficacy.