tbuckley/cabot-search huggingface dataset:
Cost limits on ancillary staff.
Authors: R. G. Drysdale
Journal: BMJ (1989)

Finally, we believe that the patient's interests are best served by having operations performed by surgeons who are suitably experienced in the particular disorder and operation concerned: their official specialty is secondary and the surgeon best satisfying these criteria currently varies from region to region.It is noteworthy that, although in the United Kingdom no specialist qualification in head and neck surgery exists, the FRCS (Otolaryngology) emphasises the subject more than its general counterpart.
Rules for Making Human Tumor Cells
Authors: William C. Hahn, Robert A. Weinberg
Journal: New England Journal of Medicine (2002)

The apparent complexity of the genetic, biochemical, and physiological changes in cancer cells threatens to stall the elucidation of the origins of cancer and the development of new treatments for malignant diseases. The authors propose a considerably simplified scheme in which only five alterations are required to transform cells from a normal to a malignant phenotype.
Chronic calcium channel blockade prevents the progression of myocardial contractile and electrical dysfunction in the cardiomyopathic Syrian hamster.
Authors: J M Capasso, E H Sonnenblick, P Anversa
Journal: Circulation Research (1990)

The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile performance in this animal model of congestive heart failure, oral verapamil therapy was instituted at 50 days of age, and treatment continued for various durations until the time of study at either 150 or 250 days of age. Left ventricular papillary muscle isometric and isotonic performance, as well as transmembrane electrical characteristics, was depressed in diseased hamsters at 150 days of age and deteriorated further by 250 days of age. These changes were evidenced by prolongation of contraction duration, a marked depression in the load-velocity relation, and a significant prolongation in the repolarization phase of the transmembrane action potential. Myocardial functional and electrical alterations associated with the progression of life in myopathic hamsters were completely halted by verapamil therapy that was continuous from 50 days after birth until death by diastolic arrest, at 150 or 250 days of age. However, premature termination of verapamil treatment before death resulted in a progressive renewal of the functional and electrical alterations for the duration of drug termination. It is concluded that the pathological changes seen during the lifetime of the cardiomyopathic hamster can be prevented by continuous calcium channel blockade and that intermediate prevention can be attained by protracted verapamil therapy. Thus, chronic verapamil therapy may be a useful adjunct in the prevention of human congestive heart failure of similar etiology.
A Critical Role for a Rho-Associated Kinase, p160ROCK, in Determining Axon Outgrowth in Mammalian CNS Neurons
Authors: Haruhiko Bito, Tomoyuki Furuyashiki, Hisamitsu Ishihara, Yoshikazu Shibasaki, Kazumasa Ohashi, Kensaku Mizuno, Midori Maekawa, Toshimasa Ishizaki, Shuh Narumiya
Journal: Neuron (2000)
Genetic test can help reduce school absences owing to asthma
Authors: K. Chinthapalli
Journal: BMJ (2013)

Genetic testing of children with asthma can identify the most effective treatment and thereby reduce asthma exacerbations, a new study shows.1

The trial found that one add-on treatment for asthma, salmeterol, was less effective than another, montelukast, in 62 Scottish children with the homozygous arginine-16 mutation. Children taking montelukast had fewer school absences resulting from asthma, had milder exacerbations, and used less of the salbutamol “reliever” inhaler over the following year.

Salmeterol and montelukast are both used in patients with symptoms …
Abstract 3254: Discovery of S3I-1757, a STAT3-STAT3 dimerization disruptor that inhibits STAT3 activity, tumor survival, migration and invasion.
Authors: Xiaolei Zhang, Ying Sun, Roberta Pireddu, Hua Yang, Murali K. Urlam, Harshani R. Lawrence, Wayne C. Guida, Nicholas J. Lawrence, Said M. Sebti
Journal: Cancer Research (2013)

Abstract The ability of STAT3 to translocate to the nucleus, bind DNA and transcriptionally regulate STAT3 target genes depends on tyrosine phosphorylation STAT3-STAT3 dimerization. Our chemistry efforts led to the discovery of S3I-1757 that disrupts STAT3-STAT3 dimerization. Fluorescence polarization assays and molecular modeling show that S3I-1757 interacts with Y-705 binding site in the STAT3-SH2 domain and displaces fluorescein-labelled GpYLPQTV phosphotyrosine peptide from binding to STAT3. Furthermore, using co-immunoprecipitation and co-localization studies we show that S3I-1757 inhibits STAT3 dimerization and STAT3-EGF receptor binding in intact cells. Treatment of human cancer cells with S3I-1757 (but not a closely related analogue, S3I-1756, that does not inhibit STAT3 dimerization), inhibits selectively the phosphorylation of STAT3 over Akt and Erk1/2, nuclear accumulation of P-Y705-STAT3, STAT3-DNA binding and transcriptional activation and suppresses the expression levels of STAT3 target genes such as Bcl-xL, survivin, cyclin D1 and MMP9. Furthermore, S3I-1757 but not S3I-1756 inhibits anchorage-dependent and -independent growth, migration and invasion of human cancer cells which depend on STAT3 selectively over those that do not. Finally, STAT3-C, a genetically engineered mutant of STAT3 that forms a constitutively dimerized STAT3, rescues from S3I-1757 effects. Our results warrant further development of S3I-1757 as a STAT3-STAT3 dimerization inhibitor capable of blocking hyper activated STAT3 and suppressing malignant transformation of STAT3-dependent human tumors. Citation Format: Xiaolei Zhang, Ying Sun, Roberta Pireddu, Hua Yang, Murali K. Urlam, Harshani R. Lawrence, Wayne C. Guida, Nicholas J. Lawrence, Said M. Sebti. Discovery of S3I-1757, a STAT3-STAT3 dimerization disruptor that inhibits STAT3 activity, tumor survival, migration and invasion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3254. doi:10.1158/1538-7445.AM2013-3254
The Peer Review Congresses
Authors: Robert Steinbrook
Journal: JAMA (2013)

Original scientific reports in peer-reviewed journals are the cornerstones of new medical knowledge. Yet medical journalism, unlike research, is not a science but rather, like medical practice, a mix of art and science. All journals face the continuing challenges of providing their readers with information they can trust, improving their systems for evaluating manuscripts, and dealing with increasing concerns about financial and intellectual conflicts of interest. Diagnosing the ills of biomedical publications and advancing solutions are the missions of the International Congresses on Peer Review and Biomedical Publication, the seventh and most recent of which was held in Chicago in September 2013, organized by The JAMA Network and the BMJ and once again led by Drummond Rennie, MD.
Sexual violence must be treated as medical emergency, charity says
Authors: J. Wise
Journal: BMJ (2009)

Sexual violence should be treated as a medical emergency, with immediate medical care universally available, says a report from the medical charity Medicins Sans Frontieres (MSF).

The report, Shattered Lives , says that the provision of medical care within days of a rape can limit health risks for the victim. Yet in many countries access to tailored health services is either severely limited or non-existent.

Thilde Knudsen, MSF adviser on sexual and reproductive health, said, “A victim of sexual violence is already suffering huge trauma and added to this is anxiety about possibly having contracted HIV or being pregnant. If they can be given fast access to medical care this can …
Section of Physiology and Dietetics.
Authors: C. H. Kleinschmidt
Journal: JAMA (1891)

To the Editor of the Journal of the American Medical Association: <h3>Dear Sir:</h3> —The Section of Physiology and Dietetics should be a mirror of the present knowledge of the American Medical Association; those members who have any new points in physiology and dietetics will please send the titles of what they propose as their contributions to the common stock of knowledge. The officers of the Section could fill the whole time with papers and demonstrations, but this would infringe on others' rights and make it too much of an individual affair. There is no prescription of subjects, as this would be a restriction on the broad and open treatment that is due to workers in this department. Still practical points as to food will be very acceptable in the hope that better days as to diet may sooner dawn.
Human serum albumin–thioredoxin fusion protein with long blood retention property is effective in suppressing lung injury
Authors: Masato Furukawa, Ryota Tanaka, Victor Tuan Giam Chuang, Yu Ishima, Kazuaki Taguchi, Hiroshi Watanabe, Toru Maruyama, Masaki Otagiri
Journal: Journal of Controlled Release (2011)
Dermoscopy of fully regressive cutaneous melanoma
Authors: N. Bories, S. Dalle, S. Debarbieux, B. Balme, S. Ronger-Savlé, L. Thomas
Journal: British Journal of Dermatology (2008)

Metastatic melanoma of unknown origin is a difficult challenge diagnostically and therapeutically. Diagnosis of the putative primary lesion is difficult. This difficulty increases when the primary lesion has undergone complete regression.To define the dermoscopic features of fully regressed melanoma.A single-institution, register-based study of an unselected consecutive series of seven cases of metastatic melanoma in the lymph nodes with no known or visible primary lesion was carried out. Skin examination included dermoscopy; when a suspicious area was found, observed dermoscopic features were recorded and a biopsy was performed. Diagnosis of completely regressive cutaneous melanoma was based on clinical-pathological correlation according to widely accepted criteria.Seven dermoscopic features were associated with completely regressive melanoma: scar-like depigmentation (100%); pink coloration of the background (100%); linear-irregular vessels (86%); globular pattern of the vessels (43%); remnants of pigmentation (86%), either macular (43%) or with a peppering aspect (43%); and white lighter transverse bands (43%). The last feature was only observed with polarized light dermoscopy devices.Dermoscopy more accurately distinguishes the vascular, pigmentary and scarring changes of fully regressive melanoma. We believe that dermoscopy should be included in the search for a regressive primary lesion in case of metastatic melanoma of unknown origin.
WHO reform and global health
Authors: F. Godlee
Journal: BMJ (1997)

The world has changed since the World Health Organisation was founded nearly 50 years ago, and the pressure on WHO to change in response has never been greater. Continuing financial constraints, growing demands on the international health system, the approach of the millennium (the deadline for the Health for All initiative), and the certainty of new leadership (see p 1367)1 in 1998, when WHO celebrates its own half century, all add to the urgency and timeliness of the debate. But what would a reformed WHO look like, and will reform mean dismantling the existing organisation and starting again? The meeting this week of the World Health Assembly in Geneva marks the beginning of a crucial year for the future of international health.

The past five years have seen the emergence of an impressive consensus about the problems of the world's health system. Analysts talk of a crisis in international health, with increasing inequities and worsening access to health care for the world's most vulnerable populations. The moves towards privatisation and tertiary care are mirrored by reduced emphasis on and provision of primary and preventive care. Lack of coordination between international agencies has meant duplication of effort, confusion, and waste of resources.

With its narrow, top down, service oriented approach to health and its centralised, hierarchical bureaucracy, WHO has proved unequal to the new challenges. Its once clear calls for equity and universal primary care have been drowned out by the World Bank's conflicting emphasis on economic growth and efficiency. Much of this can be blamed on WHO's lack of leadership and inadequate commitment from member states. In trying to please all its political constituents WHO has spread itself too thin and lost direction.2

The first formal call for reform came from within WHO in 1993,3 but since …
Leu110Pro substitution in the RhD polypeptide is responsible for the D<sup>VII</sup> category blood group phenotype
Authors: Christelle Rouillac, Caroline Le Van Kim, Marylise Beolet, Jean‐Pierre Cartron, Yves Colin
Journal: American Journal of Hematology (1995)

The nucleotide sequence of the RhD transcripts from the reticulocytes of three unrelated variants with the DVII category blood group phenotype has been determined. Our results indicate that the expression of the low frequency antigen Rh40 and the lack of epD8 at the surface of these variant RhD positive red cells are associated with a single point mutation, T329C, in exon 2 of the RHD gene. This nucleotide polymorphism results in a leucine to proline substitution at amino acid position 110 of the RhD polypeptide.
Breast Cancer and the Role of Cytokines in Regulating Estrogen Synthesis: An Emerging Hypothesis
Authors: M. J. Reed, A. Purohit
Journal: Endocrine Reviews (1997)

I. Introduction II. Peripheral Estrogen Synthesis and Blood and Tissue Estrogens in Breast Cancer A. Peripheral estrogen synthesis B. Aromatase C. Estrone sulfatase D. E2DH E. Origins of breast tumor estrogens III. Influence of Breast Tumor Location on Enzyme Activities in Adjacent Tissues IV. Proposed Model for the Regulation of Estrogen Synthesis in Breast Tumors V. Evidence in Support of Proposed Model of Cytokine Regulation of Estrogen Synthesis A. Identification of factors that stimulate estrogen synthesis B. Potentiation of cytokine stimulation of estrogen synthesis VI. The Role of Soluble Cytokine Receptors in Cytokine Action A. Mechanism of cytokine action B. Regulation of gp80 and gp130 C. Regulation of IL-6 sR shedding VII. Origin of Estrogen-Stimulating Factors in Breast Tumors A. The role of cells of the immune system B. Macrophages and lymphocytes in breast tumors VIII. Regulation of Lymphocyte Cytokine Production A. Th1 and Th2-helper cells B. Dehydroepiandrosterone (DHA) and glucocorticoids...
TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis
Authors: Gernot Kleinberger, Yoshinori Yamanishi, Marc Suárez-Calvet, Eva Czirr, Ebba Lohmann, Elise Cuyvers, Hanne Struyfs, Nadine Pettkus, Andrea Wenninger-Weinzierl, Fargol Mazaheri, Sabina Tahirovic, Alberto Lleó, Daniel Alcolea, Juan Fortea, Michael Willem, Sven Lammich, José L. Molinuevo, Raquel Sánchez-Valle, Anna Antonell, Alfredo Ramirez, Michael T. Heneka, Kristel Sleegers, Julie van der Zee, Jean-Jacques Martin, Sebastiaan Engelborghs, Asli Demirtas-Tatlidede, Henrik Zetterberg, Christine Van Broeckhoven, Hakan Gurvit, Tony Wyss-Coray, John Hardy, Marco Colonna, Christian Haass
Journal: Science Translational Medicine (2014)

Loss of TREM2 function impairs phagocytosis and correlates with decreased soluble TREM2 in biological fluids of patients with neurodegenerative disorders.
Suppression of myocardial protein degradation in the rat during fasting. Effects of insulin, glucose, and leucine.
Authors: G D Curfman, D S O'Hara, B E Hopkins, T W Smith
Journal: Circulation Research (1980)

To study the effects of leucine, glucose, and insulin on myocardial protein degradation in fed and fasted nutritional states, we developed and validated a sensitive method for measuring rates of total protein degradation in rat isolated left atrial preparations. Fasting resulted in a progressive decrease in myocardial protein breakdown to 71% of control over a 24-hour period, with no further reduction in degradation rate between 24 and 72 hours of fasting. Insulin (100 mU/ml) suppressed atrial protein degradation by 38% in fed animals (P less than 0.001) and by 51% in fasted animals (P less than 0.001). Glucose alone had no effect on protein degradation in either nutritional state. At 5 times normal plasma levels, leucine suppressed protein breakdown by 21% in fed and by 15% in fasted animals. The decrease in degradation induced by fasting and the absence of an effect of glucose are in contrast to the behavior reported for skeletal muscle.
Proteasome inhibition during myocardial infarction
Authors: X. Yu, D. C. Kem
Journal: Cardiovascular Research (2009)

The ubiquitin-proteasome system (UPS) plays a central role in protein degradation and regulates a variety of critical cellular processes. During recent years, the cardiac UPS has become increasingly recognized as a key regulator of cardiac function under both physiological and pathological conditions. Numerous studies have demonstrated that altered UPS function is involved in the pathogenesis of cardiac disease including myocardial ischaemia or infarction. The expression and activity of the E3 ubiquitin ligases, which confer substrate specificity in the UPS pathway, affect the apoptosis and severity of disease in myocardial ischaemia and reperfusion. Although impaired proteasome function is commonly associated with myocardial ischaemic injury, recent evidence also supports a cardioprotective role for proteasome inhibitors in myocardial ischaemia. We will review these studies and data, discuss controversies regarding the UPS alterations and use of proteasome inhibitors in myocardial ischaemia, and attempt to identify strategies that may enhance their clinical application.
Rise in obesity among children in England may be slowing
Authors: Z. Kmietowicz
Journal: BMJ (2009)

The rate of increase in the number of children who are obese or overweight may be starting to slow, shows a new analysis of the latest data.

In 2007 researchers predicted that by 2020 the proportion of boys aged 2 to 11 years who would be obese or overweight would be 42%. This figure has now been revised down to 30% by the National Heart Forum.

The proportion of girls aged 2 …
And for now: two innovative methods
Authors: Beverly Merz
Journal: JAMA (1983)

Two seemingly common forms of medication—a cough syrup and a plain blue tablet—represent two of the most recent innovations in oral controlled-rate drug delivery systems. The cough syrup, Delsym, in which dextromethorphan is the active ingredient, is the first representative of the Pennkinetic system to reach the market. In this system, developed by Pennwalt Corporation, Rochester, NY, a drug in an ionic state is bound to a polymer matrix. Some of the drug/polymer complex is subsequently coated with ethyl cellulose. Then a mix of coated and uncoated particles, which average about 100 μm in length, is suspended in a syrup. A patient taking a single one-teaspoon dose of the syrup swallows approximately 1 million drug/polymer particles. The drug remains unavailable until it reaches the gastrointestinal system, but once there, ions present in digestive fluids diffuse through the ethyl cellulose coat (if it is present) and bind with the polymer, displacing
Sequence Diversity at the Proximal 14q32.1 SERPIN Subcluster: Evidence for Natural Selection Favoring the Pseudogenization of SERPINA2
Authors: S. Seixas, G. Suriano, F. Carvalho, R. Seruca, J. Rocha, A. Di Rienzo
Journal: Molecular Biology and Evolution (2006)

The superfamily of serine protease inhibitors (SERPINs) plays a key role in controlling the activity of proteinases in diverse biological processes. alpha1-antitrypsin (SERPINA1), the most studied member of this family, is encoded by a gene located within the proximal 14q32.1 SERPIN subcluster, together with the highly homologous alpha1-antitrypsin-like sequence (SERPINA2), which was previously proposed to be a pseudogene. Here, we performed a resequencing study encompassing both SERPINA1 and SERPINA2 as well as the adjacent gene coding for corticosteroid-binding globulin (SERPINA6) in samples from Europe and West Africa. In the African sample, we found that a common haplotype carrying a 2-kb deletion in the SERPINA2 gene is associated with remarkable long-range homozygozity as if it was quickly driven to high frequency by natural selection acting on an advantageous variant. An analysis of the HapMap Phase I data for the Yoruba sample confirmed that variation in this subcluster carries a strong signal of positive selection. We also show that the SERPINA2 gene is expressed and probably encodes a functional SERPIN. Finally, comparisons with orthologous sequences in nonhuman primates showed that SERPINA2 is present in some great apes, but in chimpanzees it was lost by a deletion event independent from that observed in humans. In agreement with the "less is more" hypothesis, we propose that loss of SERPINA2 is an ongoing process associated with a selective advantage during recent primate evolution, possibly because of a role in fertility or in host-pathogen interactions.
18F-FDG PET-Detected Synchronous Primary Neoplasms in the Staging of Esophageal Cancer
Authors: Vinod Malik, Ciaran Johnston, Claire Donohoe, Zieta Claxton, Julie Lucey, Narayanasamy Ravi, John V. Reynolds
Journal: Clinical Nuclear Medicine (2012)

Purpose 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging is increasingly the standard of care in the staging of esophageal cancer. Synchronous neoplasms may be identified, and this study evaluated the prevalence of such tumors and their impact on management. Methods Five hundred ninety-one (73.6%) of 803 consecutive patients with biopsy-proven esophageal cancer underwent staging 18F-FDG PET or PET/CT scans. 18F–FDG-avid lesions were considered synchronous primary neoplasms if occurring at locations atypical for metastases from the known primary, a marked discordance in the 18F-FDG avidity from that of the primary tumor, and if there was no prior detection on conventional imaging. Additional investigations as appropriate were undertaken, and histopathological verification was obtained where possible to validate the suspected synchronous neoplasm. Results A synchronous neoplasm was suspected in 55 (9.3%) of 591 patients, predominantly at sites in the colon (26) and head and neck (21). Additional investigations in 43 cases revealed malignant neoplasms in 8 (18.6%), premalignant in 9 (20.9%), and benign lesions in 26 (60.5%) cases. The management plan was altered in 8 patients, 1.4% overall. The total cost of added tests was $27,482.57 (€21,024) with the decision to treat the esophageal cancer deferred by a mean of 10.7 days. Conclusion 18F-FDG uptake concerning for synchronous neoplasms is evident in approximately 1 in 10 cases, and of these a minority will represent a malignant neoplasm that significantly impacts on treatment. The overall added costs per patient are relatively modest and the treatment delay within acceptable limits of clinical practice.
An imprinted gene p57KIP2 is mutated in Beckwith–Wiedemann syndrome
Authors: Izuho Hatada, Hirofumi Ohashi, Yoshimitsu Fukushima, Yasuhiko Kaneko, Masahiro Inoue, Yosuke Komoto, Akira Okada, Sachiko Ohishi, Akira Nabetani, Hiroko Morisaki, Masahiro Nakayama, Norio Niikawa, Tsunehiro Mukai
Journal: Nature Genetics (1996)