tbuckley/cabot-search huggingface dataset:
Counselling failed exam candidates: Candidates choose when to stop
Authors: R. Ellis
Journal: BMJ (1993)

shown would be equivalent to (and hence would obscure) about two weeks and six months of normal weight gain in babyhood and mid- childhood respectively; when being weighed, infants should be naked and children should wear minimum clothing compatible with modesty.Despite the expensive apparatus featured in the photographs measurements of height as shown would be only an approximation of the true value, making any later inferences about rate of growth meaningless.At a time when paediatricians and the govem- ment are trying to promote high quality child health surveillance such illustrations serve only to underline how much basic education still needs to be given to those who should know better.
Inspiratory Impedance During Active Compression-Decompression Cardiopulmonary Resuscitation
Authors: Patrick Plaisance, Keith G. Lurie, Didier Payen
Journal: Circulation (2000)

Background —Blood pressure is severely reduced in patients in cardiac arrest receiving standard cardiopulmonary resuscitation (CPR). Although active compression-decompression (ACD) CPR improves acute hemodynamic parameters, arterial pressures remain suboptimal with this technique. We performed ACD CPR in patients with a new inspiratory threshold valve (ITV) to determine whether lowering intrathoracic pressures during the “relaxation” phase of ACD CPR would enhance venous blood return and overall CPR efficiency. Methods and Results —This prospective, randomized, blinded trial was performed in prehospital mobile intensive care units in Paris, France. Patients in nontraumatic cardiac arrest received ACD CPR plus the ITV or ACD CPR alone for 30 minutes during advanced cardiac life support. End tidal CO 2 (ETCO 2 ), diastolic blood pressure (DAP) and coronary perfusion pressure, and time to return of spontaneous circulation (ROSC) were measured. Groups were similar with respect to age, gender, and initial rhythm. Mean maximal ETCO 2 , coronary perfusion pressure, and DAP values, respectively (in mm Hg), were 13.1±0.9, 25.0±1.4, and 36.5±1.5 with ACD CPR alone versus 19.1±1.0, 43.3±1.6, and 56.4±1.7 with ACD plus valve ( P &lt;0.001 between groups). ROSC was observed in 2 of 10 patients with ACD CPR alone after 26.5±0.7 minutes versus 4 of 11 patients with ACD CPR plus ITV after 19.8±2.8 minutes ( P &lt;0.05 for time from intubation to ROSC). Conclusions —Use of an inspiratory resistance valve in patients in cardiac arrest receiving ACD CPR increases the efficiency of CPR, leading to diastolic arterial pressures of &gt;50 mm Hg. The long-term benefits of this new CPR technology are under investigation.
Reproducible Porcine Model of Thoracic Aortic Aneurysm
Authors: Shaina R. Eckhouse, Christina B. Logdon, J. Marshall Oelsen, Risha K. Patel, Allison D. Rice, Robert E. Stroud, W. Benjamin Wince, Rupak Mukherjee, Francis G. Spinale, John S. Ikonomidis, Jeffrey A. Jones
Journal: Circulation (2013)

Background— Thoracic aortic aneurysms (TAAs) develop secondary to abnormal aortic extracellular matrix remodeling, resulting in a weakened and dilated aortic wall that progressed to rupture if left unattended. Currently, no diagnostic/prognostic tests are available for the detection of TAA disease. This is largely driven by the lack of a large animal model, which would permit longitudinal/mechanistic studies. Accordingly, the objective of the present study was to establish a reproducible porcine model of aortic dilatation, which recapitulates the structural and biochemical changes observed during human TAA development. Methods and Results— Descending TAAs were induced in Yorkshire pigs (20–25 kg; n=7) through intra-adventitial injections of collagenase (5 mL, 0.35 mg/mL) and periadventitial application of crystalline CaCl 2 (0.5 g). Three weeks after TAA induction, aortas were harvested and tissue was collected for biochemical and histological measurements. A subset of animals underwent MRI preoperatively and at terminal surgery. Results were compared with sham-operated controls (n=6). Three weeks after TAA induction, aortic luminal area increased by 38±13% ( P =0.018 versus control). Aortic structural changes included elastic lamellar degradation and decreased collagen content. The protein abundance of matrix metalloproteinases 3, 8, 9, and 12 increased in TAA tissue homogenates, whereas tissue inhibitors of metalloproteinases 1 and 4 decreased. Conclusions— These data demonstrate aortic dilatation, aortic medial degeneration, and alterations in matrix metalloproteinase/tissue inhibitors of metalloproteinase abundance, consistent with TAA formation. This study establishes for the first time a large animal model of TAA that recapitulates the hallmarks of human disease and provides a reproducible test bed for examining diagnostic, prognostic, and therapeutic strategies.
From essential to persistent genes: a functional approach to constructing synthetic life
Authors: Carlos G. Acevedo-Rocha, Gang Fang, Markus Schmidt, David W. Ussery, Antoine Danchin
Journal: Trends in Genetics (2012)

A central undertaking in synthetic biology (SB) is the quest for the 'minimal genome'. However, 'minimal sets' of essential genes are strongly context-dependent and, in all prokaryotic genomes sequenced to date, not a single protein-coding gene is entirely conserved. Furthermore, a lack of consensus in the field as to what attributes make a gene truly essential adds another aspect of variation. Thus, a universal minimal genome remains elusive. Here, as an alternative to defining a minimal genome, we propose that the concept of gene persistence can be used to classify genes needed for robust long-term survival. Persistent genes, although not ubiquitous, are conserved in a majority of genomes, tend to be expressed at high levels, and are frequently located on the leading DNA strand. These criteria impose constraints on genome organization, and these are important considerations for engineering cells and for creating cellular life-like forms in SB.
Efficacy of Total Colonoscopy with a Transparent Cap in Comparison with Colonoscopy without the Cap
Authors: M. Matsushita, K. Hajiro, K. Okazaki, H. Takakuwa, M. Tominaga
Journal: Endoscopy (1998)

Background and Study Aims: In spite of scrupulous inspection during routine colonoscopy, small lesions behind the semilunar folds can be situated in blind spots, where they are easily overlooked. The aim of this study was to evaluate the efficacy of total colonoscopy with a transparent cap in identifying such lesions, in comparison with colonoscopy without the cap.
Turning on LIGHT
Authors: Steve W. Granger, Carl F. Ware
Journal: Journal of Clinical Investigation (2001)

The delicate balance between the proliferation and elimination of antigen-activated lymphocytes achieves homeostasis in peripheral lymphoid tissues. The TNF-related cytokines activate cellular differentiation, survival, and death pathways that orchestrate tissue development, organization, and homeostasis (1). Several members of the TNF superfamily of cytokines play opposing roles in lymphocyte homeostasis by enhancing effector cell activation and survival, or by cellular elimination through apoptosis.
SOME PROPERTIES OF THE ENCEPHALOPATHIC AGENT IN PRIMATE BONE MARROW (THE GORDON AGENT)
Authors: Lester S. King
Journal: The Journal of Experimental Medicine (1940)

The nature of the encephalopathic agent present in monkey bone marrow has been investigated. It is readily soluble at a pH of 7.4, as well as at the low pH of 2.0 and 3.0. The point of minimal solubility is pH 4.2. Heat inactivation is produced by a temperature of 75 degrees C., acting for 15 minutes. The agent is digested by pepsin. It exhibits a slight degree of sedimentation with the air-driven centrifuge. It is non-dialyzable. It is precipitated from solution (pH 7.4) by ammonium sulfate, over a range of 0.4 to 0.8 saturation. These findings all suggest that the agent is a protein. No immunological reactions could be elicited.
Acknowledgments to departments of pathology
Authors: D N Baron
Journal: BMJ (1982)

and no case has yet manifested pelvic wall or suture-line disease.None of these cases has received either cytotoxic or radiotherapeutic adjuvant therapy.Our figures suggest that all but a minority of rectal cancers may be controlled locally by refinement of surgical technique.If this is so we might most profitably direct the adjuvant treatments towards the abortion of hepatic micrometastases in the manner which has been advocated by Taylor and others.2It is surely desirable that we should approach this slow-growing and often localised disease in a stepwise manner and evaluate each modality in turn.In particular trials of adjuvant therapy are unlikely to bear fruit until the surgical technique has been standardised so that we may compare like with like.
A new mental health (and public protection) act
Authors: G. Szmukler
Journal: BMJ (2001)

The 1959 Mental Health Act marked a transition from the “legalism” of the 1890 Lunacy Act, with its 19th century libertarian concerns, to a welfare statute in which decisions about involuntary treatment for mental disorders became primarily a matter for doctors.1 In the Mental Health Act 1983 a revived form of legalism set some limits to medical discretion. Now a white paper, Reforming the Mental Health Act , promises a new epoch, one where “concerns of risk will always take precedence, but care and treatment provided under formal powers should otherwise reflect the best interests of the patient.”2 The foreword to a preview of the “biggest shake up in mental health legislation for four decades” is signed by both the health and the home secretaries, and half the paper is devoted to “high risk patients.” Perceived failures in community care are the main drivers.

We will see big changes. A simpler template for “formal assessment” followed by a care and treatment order, applicable in both civil and criminal justice settings, is described. Everyone, including patients and carers, should find it easier to understand. The definition of mental disorder is very broad—”any disability or disorder of mind or brain, whether permanent or temporary, which results in an impairment or disturbance of mental functioning.” Personality disorder is clearly included. The criteria for a …
A NOTE UPON THE GROWTH OF PNEUMOCOCCI AND STREPTOCOCCI IN BLOOD SERUM
Authors: Warfield T. Longcope
Journal: The Journal of Experimental Medicine (1905)

During the investigations described in another paper defibrinated blood and blood serum were frequently used, either alone or mixed with agar, as media upon which to grow pneumoeocci and streptococci. It was immediately noted that the organisms grew very differently in serum obtained from different individuals. The variations were so marked and the results obtained so striking that it was decided to study the matter more carefully. To this end the growth of pneumococci and streptococci was studied in the blood serum of thirty-two individuals. Besides the human sera, horse's serum, calf's serum, and rabbit's serum were used. In the researches conducted by Besangon and Griffon, 1 Huber, 2 Neufeld, 3 and Wadsworth 4 upon the agglutination of pneumococci by the serum of pneumonia patients and of immunized animals, certain changes besides the actual agglutination were noted in the bacteria and serum. Huber in particular calls attention to the heavy precipitate formed by growing pneumococci in pneumonic serum, a phenomenon which did not occur in the serum from normal individuals, when used as a culture medium for pneumococci. Neufeld describes swelling of the capsules of the pneumococci when treated with the serum from cases of pneumonia or from immunized animals. Wadsworth has confirmed these observations. Recently Rosenow s has called attention to another very interesting result of the
Soothing signals: transplacental transmission of resistance to asthma and allergy
Authors: Patrick G. Holt, Deborah H. Strickland
Journal: The Journal of Experimental Medicine (2009)

The progressive rise in the prevalence of allergic diseases since the 1970s is widely attributed to diminished exposure to microbial stimuli, resulting in dysregulated immune functions during early life. Most studies investigating the mechanism behind this phenomenon have focused on postnatal microbial exposure. But emerging evidence suggests that such programming may also occur in the developing fetus as a result of microbial stimulation of the pregnant mother.
Free Tubulin Modulates Mitochondrial Membrane Potential in Cancer Cells
Authors: Eduardo N. Maldonado, Jyoti Patnaik, Matthew R. Mullins, John J. Lemasters
Journal: Cancer Research (2010)

Abstract Formation of the mitochondrial membrane potential (ΔΨ) depends on flux of respiratory substrates, ATP, ADP, and Pi through voltage-dependent anion channels (VDAC). As tubulin promotes single-channel closure of VDAC, we hypothesized that tubulin is a dynamic regulator of ΔΨ, which in cultured cancer cells was assessed by confocal microscopy of the potential-indicating fluorophore tetramethylrhodamine methylester (TMRM). Microtubule destabilizers, rotenone, colchicine, and nocodazole, and the microtubule stabilizer paclitaxel increased and decreased cellular free tubulin, respectively, and in parallel decreased and increased ΔΨ. Protein kinase A (PKA) activation by cAMP analogues and glycogen synthase kinase 3β (GSK-3β) inhibition decreased ΔΨ, whereas PKA inhibition hyperpolarized, consistent with reports that PKA and GSK-3β decrease and increase VDAC conductance, respectively. Plasma membrane potential assessed by DiBAC4(3) was not altered by any of the treatments. We propose that inhibition of VDAC by free tubulin limits mitochondrial metabolism in cancer cells. Cancer Res; 70(24); 10192–201. ©2010 AACR.
The Impact of Holistic Medicine, Medical Groups, and Health Concepts
Authors: George Yahn
Journal: JAMA (1979)

Holistic medicine (Greek,<i>holos</i>, meaning entire or whole) focuses on the whole person—mind-body-spirit, well-being, and wellness. It is a new health care movement or medical approach that is gaining momentum. The basic concepts are simple and clear, avoiding a piecemeal approach to health with treatment of one disease. Two or three physicians may form holistic medical groups, sometimes inviting nonphysician health care professionals to join. Some of these nonphysicians are not licensed, and standards need to be devised. Governmental agencies are impressed by low-cost results, especially with chronically ill patients. There are also groups that have spiritual health care modalities and ministrations. Nevertheless, there are commercialistic tendencies and faddism in some centers, and the literature has been criticized as being for laymen by laymen; however, the movement deserves a sympathetic hearing. (<i>JAMA</i>242:2202-2205, 1979)
Denis Wilson Robertson
Authors: Derek Bull
Journal: BMJ (2006)

​FormerFormer general practitioner Northampton (b Rhyl, north Wales, 1925; q St Mary's Hospital, London, 1950; MRCGP, Cert Aviat Med), died from cancer on 6 November 2005.



Figure 1



After qualifying Denis joined his father in general practice, retiring in 1990. Interested in dental anaesthetics, he developed a large practice among local dental surgeons. Having learnt to fly, he held a private pilot's licence from 1960, and was appointed an authorised medical examiner for the Civil Aviation Authority in 1965. He was a clinical assistant in surgery at Northampton General Hospital for several years. Appointed a magistrate in 1968, he became chairman of the Northampton Bench in 1993. He leaves a wife, Marjorie, and two daughters.
Abstract 2137: Prevention of HER2 overexpressing early stage breast disease progression by lapatinib
Authors: Jia Xu, Shalini Jain, Dihua Yu
Journal: Cancer Research (2014)

Abstract Currently, Tamoxifen and Aromatase inhibitors are used for prevention of estrogen receptor positive (ER+) breast cancer; however, there is no effective prevention strategy for ER- breast cancer. HER2 overexpression (HER2+) can be detected in up to 60% early stage breast lesions, such as atypical hyperplasia (ADH) and ductal carcinoma in situ (DCIS). Up to 40% of ER- breast cancers are HER2+. Thus, targeting HER2 signaling may be an effective chemoprevention strategy for these ER- and HER2+ breast cancer. Here, we stable introduced ErbB2-expressing retroviruses into the ER-, non-transformed MCF10A cells (MCF10A.B2) to establish an ER- and HER2+ early breast disease model. We show that Lapatinib, a FDA-approved dual tyrosine kinase inhibitor for both HER2 and EGFR, reduced the proliferation rate and increased the apoptosis in MCF10A.B2 cells. In 3D culture, Lapatinib treatment starting at day 6 prevented the MCF10A.B2 cells from forming abnormal acini, and the numbers of DCIS-like acini have been significantly decreased compared to control group. Untreated MCF10A.B2 cells forms DCIS-like acini in 3D culture by day 10, which have been reverted to normal or ADH-like acini when lapatinib treatment started by day 10. Furthermore, MMTV-neu mouse model develop ER- mammary tumors in 6.4 months, whereas lapatinib treatment (30mg/kg/day, six days per week) starting at 10 weeks of age significantly delayed the tumor initiation and progression in this mouse model as detected by mammary gland biopsy and fiber optic micro-endoscope (FOME) imaging. Mice treated with lapatinib had fewer premalignant lesions and reduced noninvasive tumors in their mammary glands, which are correlated with reduced proliferation rate and increased apoptosis rate, indicating that lapatinib is a promising agent for the prevention/intervention of ER- and HER2+ breast cancers. To identify effective and reliable biomarkers to assess the risk of ER-/HER2+ lesions and efficacy of lapatinib for prevention and intervention, cDNA microarray and reverse phase protein array (RPPA) were performed on MCF10A.B2 cells and control MCF10A cells. We have identified several molecular pathways activated by HER2+ in this model which will be tested for their roles in the initiation of mammary tumors and as potential targets for prevention of ER-/HER2+ breast disease. Our study brings better understanding of the mechanism underlying ER-/HER2+ early stage breast disease progression to cancer and could be rapidly translated into the clinic for prevention of ER-/HER2+ breast cancers. Citation Format: Jia Xu, Shalini Jain, Dihua Yu. Prevention of HER2 overexpressing early stage breast disease progression by lapatinib. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2137. doi:10.1158/1538-7445.AM2014-2137
Cytotoxic T lymphocytes (CTL) against a transforming gene product select for transformed cells with point mutations within sequences encoding CTL recognition epitopes.
Authors: N L Lill, M J Tevethia, W G Hendrickson, S S Tevethia
Journal: The Journal of Experimental Medicine (1992)

The 94-kD large tumor (T) antigen specified by simian virus 40 (SV40) is sufficient to induce cell transformation. T antigen contains four H-2Db-restricted cytotoxic T lymphocyte (CTL) recognition epitopes that are targets for CTL clones Y-1, Y-2, Y-3, and Y-5. These epitopes have been mapped to T antigen amino acids 207-215 (site I), 223-231 (sites II and III), and 489-497 (site V), respectively. Antigenic site loss variant cells that had lost one or more CTL recognition epitopes were previously selected by coculturing SV40-transformed H-2Db cells with the site-specific Db-restricted CTL clones. The genetic bases for T antigen CTL recognition epitope loss from the variant cells were identified by DNA amplification and direct sequencing of epitope-coding regions from variant cell DNAs. Cells selected for resistance to CTL clone Y-1 (K-1; K-1,4,5; K-3,1) carry deleted SV40 genomes lacking site I, II, and III coding sequences. Point mutations present within the site II/III coding region of Y-2-/Y-3-resistant cell lines specify the substitution of asparagine for lysine as T antigen amino acid 228 (K-2) or phenylalanine for tyrosine at position 230 (K-3). Point mutations identified within independently selected Y-5 resistant populations (K-5 and K-1,4,5) direct the substitution of isoleucine for asparagine at position 496 (K-5) or the substitution of phenylalanine for isoleucine at position 491 (K-1,4,5) of T antigen. Each substitution causes loss of the relevant CTL recognition epitope, apparently by compromising CTL T cell receptor recognition. These experiments identify specific amino acid changes within a transforming protein that facilitate transformed cell escape from site-specific CTL clones while allowing maintenance of cellular transformation. This experimental model system provides unique opportunities for studying mechanisms of transformed cell escape from active immunosurveillance in vivo, and for analysis of differential host immune responses to wild-type and mutant cell-transforming proteins.
Anti-CD3ε mAb improves thymic architecture and prevents autoimmune manifestations in a mouse model of Omenn syndrome: therapeutic implications
Authors: Veronica Marrella, Pietro L. Poliani, Elena Fontana, Anna Casati, Virginia Maina, Barbara Cassani, Francesca Ficara, Manuela Cominelli, Francesca Schena, Marianna Paulis, Elisabetta Traggiai, Paolo Vezzoni, Fabio Grassi, Anna Villa
Journal: Blood (2012)
The effects ex vivo and in vitro of insulin and C-peptide on Na/K adenosine triphosphatase activity in red blood cell membranes of type 1 diabetic patients
Authors: A. Djemli-Shipkolye, P. Gallice, T. Coste, M.F. Jannot, M. Tsimaratos, D. Raccah, P. Vague
Journal: Metabolism (2000)
Crossing the Divide From Vaccine Technology to Vaccine Delivery
Authors: Walter A. Orenstein
Journal: JAMA (1994)

On May 14, 1796, Edward Jenner performed the first successful vaccination against smallpox with virus obtained from a woman infected with cowpox. In the almost 200 years since that sentinel event, smallpox has been eradicated and polio has been eliminated from the Americas. Sophisticated biotechnology has brought us hepatitis B vaccine, the first licensed vaccine developed using recombinant DNA techniques. New technology has permitted linkage of<i>Haemophilus influenzae</i>type b capsular polysaccharide to protein carriers to improve the immune response of infants, and<i>H influenzae</i>type b invasive disease has been reduced by more than 95% in the 5 years since introduction of the first conjugate vaccines.<sup>1</sup>As reported by Granoff et al<sup>2</sup>in this issue ofThe JOURNAL, research continues into improving the already excellent immune response to these conjugate vaccines. While much more remains to be done in developing new and improved vaccines, the system of
Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci
Authors: Jason D Cooper, Deborah J Smyth, Adam M Smiles, Vincent Plagnol, Neil M Walker, James E Allen, Kate Downes, Jeffrey C Barrett, Barry C Healy, Josyf C Mychaleckyj, James H Warram, John A Todd
Journal: Nature Genetics (2008)