tbuckley/cabot-search huggingface dataset:
Landmark perspective: Patent ductus arteriosus
Authors: R. Warren
Journal: JAMA (1984)

<h3>THE PROFESSIONAL SETTING</h3> August 1938! Few physicians of today can be fully aware of the forces at play on a surgeon contemplating a new procedure in that year. Even those of us still alive who were active then find it difficult to recreate the setting. I will try to recall some conditions and events. <h3>Anesthesia</h3> Intratracheal positive pressure anesthesia had developed to formal acceptance only six years before as the safest way to facilitate intrathoracic procedures. The story of the emergence of that technique paralleled and controlled that of intrathoracic surgery. Rehn's<sup>1</sup>semielective repair of a 1.5-cm stab wound of the right ventricle in 1896, usually cited as the first successful operation on the heart, had been done rapidly while the patient was under ether without positive pressure. The left lung collapsed but the patient survived, the lung presumably expanding satisfactorily postoperatively. A few emergency intrathoracic procedures, such as
Obesity and risk of pneumonia in patients with influenza
Authors: I. Schreter, P. Kristian, R. Tkacova
Journal: European Respiratory Journal (2011)

To the Editors:

In a recent issue of the European Respiratory Journal , Kornum et al. 1 demonstrated a strong association between obesity and increased risk of subsequent hospitalisation with pneumonia in a prospective cohort of 48,551 subjects in Denmark. Nevertheless, adjustment for major chronic diseases eliminated the association between obesity and pneumonia risk. Interestingly, although obesity was related to increased pneumonia risk in patients with pandemic influenza A (H1N1) infection in 2009 2 it remains unclear whether higher risk of increased disease severity can be explained by the occurrence of other chronic diseases in such patients. Therefore, we analysed the role of obesity in the development of pneumonia in a cohort of 158 patients hospitalised with H1N1 infection in 2009 at …
Exercise and Posture-Related Changes of Atrial Natriuretic Factor and Cardiac Function in Diabetes
Authors: Julian E Donckier, Patrick M De Coster, Martin Buysschaert, Denis P Pieters, Franscisca M Cauwe, Annie Robert, Christine M Brichant, Adrien C Berbinschi, Jean-Marie Ketelslegers
Journal: Diabetes Care (1989)

To study whether the release of atrial natriuretic factor (ANF) was altered in diabetic cardiac autonomic neuropathy (CAN), we determined plasma ANF concentrations during exercise and changes of posture in three groups of age- and sex-matched subjects (9 healthy subjects, 7 diabetic patients with CAN, and 7 diabetic patients without CAN). During exercise, plasma ANF concentrations rose threefold (P less than .001), and this increase was similar in the three groups. However, heart-rate response to exercise was impaired in the two groups of diabetic patients (P less than .004 vs. healthy subjects) but was more severely impaired in patients with CAN (P less than .03 vs. patients without CAN). In healthy subjects and patients without CAN, the increases of ANF during exercise correlated significantly with those of heart rate, systolic blood pressure, and rate-pressure product (P less than .01). In patients with CAN, the correlation was found exclusively with heart rate (P less than .01). An increase of ventricular ejection fraction occurred in all groups (P less than .001) but without showing statistical differences between groups. After 30 min of standing, a similar postural drop of plasma ANF concentrations (P less than .002) was observed in all subjects, reflecting preserved sympathetic control of vessels. In conclusion, exercise induces an increase of plasma ANF in diabetic patients with CAN. This increase, occurring similarly to healthy subjects, indicates that autonomic activation plays a minor role in ANF release during exercise. Impaired heart-rate response to exercise in patients without CAN suggests early damage of autonomic function, undetected by conventional rest tests.
Phenotypic determinants of uncontrolled asthma
Authors: Valérie Siroux, Anne Boudier, Jean Bousquet, Jean-Louis Bresson, Jean-Luc Cracowski, Joane Ferran, Frédéric Gormand, Jocelyne Just, Nicole Le Moual, Sophie Morange, Rachel Nadif, Marie-Pierre Oryszczyn, Christophe Pison, Pierre Scheinmann, Raphaëlle Varraso, Daniel Vervloet, Isabelle Pin, Francine Kauffmann
Journal: Journal of Allergy and Clinical Immunology (2009)
Abstract 4569: Amplicon-targeted ultra-deep sequencing for the detection of KRAS, BRAF, and PIK3CA actionable mutations
Authors: Amber C. Donahue, Anthony D. Sferruzza
Journal: Cancer Research (2012)

Abstract Background: Next-generation deep sequencing techniques have the potential to revolutionize clinical testing, especially in the arena of mutation detection. Molecular diagnostic testing for KRAS, BRAF, and PIK3CA mutations has become an integral part of clinical practice for the determination of treatment eligibility for anti-EGFR therapy. Purpose: Here we investigate the feasibility of ultra-deep advanced sequencing with the 454 GS Junior instrument (454 Life Sciences/Roche, Branford CT) for the simultaneous detection of actionable mutations in KRAS, BRAF, and PIK3CA in formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissue. Methods: Advanced sequencing with a 4-amplicon panel was performed on 17 de-identified residual FFPE colorectal cancer biopsy specimens originally submitted for mutation analysis of one or more genes by standard sequencing. The 4-amplicon panel was multiplexed for up to 4 samples through “barcoding” with molecular identifier (MID) sequences, for a total of 16 amplicons per run. Results: Sequence analysis with ultra-deep coverage of 3000-5000 reads detected KRAS mutations in 5 (29%) tumor specimens, BRAF mutations in 3 (18%), and PIK3CA mutations in 4 (24%). Ten cases had a single mutation and one had two: PIK3CA E545K and BRAF D594G. Coverage was equivalent for each of the four amplicons, and in both the forward and reverse directions, providing a high level of confidence for each mutation detected. Sequencing data was obtained for each sample tested. When sample quantity allowed, Sanger sequencing and/or castPCR (Life Technologies, Grand Island, NY) were performed as method comparisons, and results were concordant. Conclusions: The use of MIDs with ultra-deep advanced sequencing allowed the simultaneous detection of mutations in multiple amplicons from multiple patients in a single sequencing run. This proof-of-concept study confirmed that using advanced sequencing to simultaneously test for multiple biomarkers in one FFPE sample is feasible, and that amplicon-based advanced sequencing is a robust and high-throughput platform for the detection of clinically actionable mutations. 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 4569. doi:1538-7445.AM2012-4569
Halting the interaction between vascular endothelial growth factor and its receptors attenuates liver carcinogenesis in mice
Authors: Hitoshi Yoshiji, Shigeki Kuriyama, Junichi Yoshii, Yasuhide Ikenaka, Ryuichi Noguchi, Daniel J. Hicklin, Yan Wu, Koji Yanase, Tadashi Namisaki, Mitsuteru Kitade, Masaharu Yamazaki, Hirohisa Tsujinoue, Tsutomu Masaki, Hiroshi Fukui
Journal: Hepatology (2004)

It has been shown that angiogenesis plays an important role not only in tumor growth, but also in early carcinogenesis. The expression of a potent angiogenic factor, vascular endothelial growth factor (VEGF), increased during the early stage of carcinogenesis. In this study, the effects of the neutralizing monoclonal antibodies R1 mAb and R2 mAb of the VEGF receptors Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), respectively, on murine hepatocarcinogenesis induced by diethylnitrosamine (DEN) were examined. The effects of R1 mAb and R2 mAb on spontaneous lung metastasis from hepatocellular carcinoma (HCC) were also investigated. VEGF expression and neovascularization in the tumor increased stepwise during hepatocarcinogenesis. Treatment with both R1 mAb and R2 mAb markedly inhibited the development of HCC and adenoma in the liver. The inhibitory effect of R2 mAb was more potent than that of R1 mAb, and the combination treatment with both mAbs almost completely attenuated hepatocarcinogenesis. Both R1 mAb and R2 mAb treatment significantly suppressed the development of angiogenesis in HCC. The suppressive effects against angiogenesis R1 mAb and R2 mAb were similar in magnitude to their inhibitory effects against hepatocarcinogenesis. Furthermore, spontaneous lung metastasis from HCC was also significantly suppressed by R1 mAb and R2 mAb treatment. In conclusion , these results suggest that VEGF and receptor interaction plays an important role in hepatocarcinogenesis and in spontaneous lung metastasis from HCC. (Hepatology 2004;39:1517-1524.)
Cytokine Balance in the Lungs of Patients with Acute Respiratory Distress Syndrome
Authors: WILLIAM Y. PARK, RICHARD B. GOODMAN, KENNETH P. STEINBERG, JOHN T. RUZINSKI, FRANK RADELLA, DAVID R. PARK, JEROME PUGIN, SHAWN J. SKERRETT, LEONARD D. HUDSON, THOMAS R. MARTIN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Acute respiratory distress syndrome (ARDS) involves an intense inflammatory response in the lungs, with accumulation of both pro- and antiinflammatory cytokines in bronchoalveolar lavage fluid (BALF). Our goal was to determine how the balance between pro- and antiinflammatory mediators in the lungs changes before and after the onset of ARDS. We identified 23 patients at risk for ARDS and 46 with established ARDS and performed serial bronchoalveolar lavage (BAL). We used immunoassays to measure tumor necrosis factor alpha (TNF-alpha) and soluble TNF-alpha receptors I and II; interleukin 1 beta (IL-1 beta), IL-1 beta receptor antagonist, and soluble IL-1 receptor II; IL-6 and soluble IL-6 receptor; and IL-10. We used sensitive bioassays to measure net TNF-alpha, IL-1 beta, and IL-6 activity. Although individual cytokines increased before and after onset of ARDS, greater increases occurred in cognate receptors and/or antagonists, so that molar ratios of agonists/antagonists declined dramatically at the onset of ARDS. The molar ratios remained low for 7 d or longer, limiting the activity of soluble IL-1 beta and TNF-alpha in the lungs at the onset of ARDS. This significant antiinflammatory response early in ARDS may provide a key mechanism for limiting the net inflammatory response in the lungs.
Staphylococcal Toxoid for Furunculosis
Authors: L. Forman
Journal: BMJ (1963)

Analgesic Drugs for Rheumatism SIR,-Your article on analgesic drugs for rheumatism (" To-day's Drugs," November 23, p. 1317) dismisses the role of steroids in the treatment of rheumatoid arthritis in surprisingly curt fashion.It says, " Long-term trials under controlled conditions show little superiority for pred- nisone' and none for cortisone2 over aspirin in conventional doses."Anyone who has enjoyed more than theoretical experience in this field surely knows that this statement merely perpetuates a statistical understatement which was long since disproved in practice.-Iam, etc., W. S. C. COPEMAN.
Functional Flexibility in T Cells
Authors: Yasmina Laouar, I.Nicholas Crispe
Journal: Immunity (2000)

Proliferation and differentiation of CD4+ T cells are often correlated, but it is not clear whether they are mechanistically linked. When antigen-specific T cells are present at high frequency in vivo, they all respond to antigenic peptide stimulation by expressing activation markers, but only a subset begins to proliferate. However, noncycling cells may synthesize the effector cytokine IFNγ even though their cell cycle is blocked in G1. These data show that proliferation and effector function are not rigidly linked in T cells. Instead, CD4+ T cells have the flexibility to engage in or bypass clonal expansion based on the integration of multiple signals, including the frequency of other responding T cells.
Timing of De Novo Mutagenesis — A Twin Study of Sodium-Channel Mutations
Authors: Lata Vadlamudi, Leanne M. Dibbens, Kate M. Lawrence, Xenia Iona, Jacinta M. McMahon, Wayne Murrell, Alan Mackay-Sim, Ingrid E. Scheffer, Samuel F. Berkovic
Journal: New England Journal of Medicine (2010)

De novo mutations are a cause of sporadic disease, but little is known about the developmental timing of such mutations. We studied concordant and discordant monozygous twins with de novo mutations in the sodium channel α1 subunit gene (SCN1A) causing Dravet's syndrome, a severe epileptic encephalopathy. On the basis of our findings and the literature on mosaic cases, we conclude that de novo mutations in SCN1A may occur at any time, from the premorula stage of the embryo (causing disease in the subject) to adulthood (with mutations in the germ-line cells of parents causing disease in offspring).
PROGRESS IN THERAPEUTICS AND ALLIED BRANCHES.
Authors: Hobart Amory Hare
Journal: JAMA (1899)

obstetrics, that exaggeration and inerrancy of technic are soon enlightened before they are permitted an ex¬ pensive experimentation to prove their want of virtue.Finally, so general has been the progress of obstetrics in all its branches that the obstetrician of to-day can truly claim to be an adept in his profession, for by his works he has gained the good opinion of the "female world."Congratulations to the unknown and known,
Points: Violence and mental illness
Authors: M. Weller
Journal: BMJ (1984)

known inhibitors of the enzyme-for example, isoniazide.Isoniazide interferes with the ALA- synthase coenzyme, pyridoxal phosphate, and, chronically administered, has a potent inhibitory effect on the hepatic enzyme in guinea pigS.2 3 I know of no trial concerning the effect of the drug in acute porphyria, either clinical or experimental.
Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs
Authors: Anais Girard-Gagnepain, Fouzia Amirache, Caroline Costa, Camille Lévy, Cecilia Frecha, Floriane Fusil, Didier Nègre, Dimitri Lavillette, François-Loïc Cosset, Els Verhoeyen
Journal: Blood (2014)
Abstract 108: Functional characterization of WAC, a candidate tumor suppressor gene in colorectal cancer
Authors: Caitlin B. Conboy, Julia M. Hatler, Pat M. Scott, Aaron L. Sarver, Kevin A. Silverstein, Somasekar Seshagiri, Matthew Adams, Jenna Lillemoe, Casey R. Dorr, Robert T. Cormier, Tim K. Starr, David A. Largaespada
Journal: Cancer Research (2012)

Abstract Broadening our understanding of the genetic basis of cancer will facilitate construction of relevant pre-clinical models and provide novel targets for drug development. To identify genes that contribute to the initiation or progression of colorectal cancer (CRC) when mutated or dysregulated, we recently conducted a set of forward genetic screens using transposon insertional mutagenesis to drive intestinal tumor formation in mice. These studies were designed to identify novel cancer genes that function in a wildtype genetic context or cooperate with known predisposing alleles (ApcMin/+ or Trp53R270H/+). Over 150 genes were identified, including several known to be important in human CRC (eg. APC, PTEN, and FBXW7) and many novel candidate cancer genes. WW domain containing adaptor with coiled-coil (WAC), is a gene not previously associated with cancer that was identified in all three screens. While the function of WAC is incompletely understood, previous reports indicate that the WAC protein participates in multiple cellular processes, including golgi biogenesis, modulation of gene expression, and induction of p21CIP1 expression and cell cycle arrest in response to DNA damage. In this study, we evaluated the role of WAC in cellular transformation by depleting WAC in mouse colonic epithelial cells conditionally immortalized by expression of a temperature sensitive SV40 large T antigen. In this model, loss of WAC expression increased anchorage-independent growth of colonic epithelial cells in cooperation with mutant APC. In human CRC samples, resequencing the WAC gene identified non-silent mutations in 2 of 74 samples. Further, CRC-associated WAC mutants were found to be functionally deficient in induction of p21CIP1 in a zebrafish embryo model. These data are consistent with the model that WAC functions as a tumor suppressor in the colonic epithelium. 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 108. doi:1538-7445.AM2012-108
Treatment of adult respiratory distress syndrome: plea for rescue therapy of the alveolar epithelium
Authors: Y. Berthiaume, O. Lesur, A. Dagenais
Journal: Thorax (1999)

Although much has been learned about the mechanisms leading to acute lung injury, mortality—which is mainly related to sepsis or associated non-pulmonary organ dysfunction1—remains high (around 50%) in patients with adult respiratory distress syndrome (ARDS).2-4 Many new therapeutic approaches aiming to control the inflammatory response accompanying ARDS have been evaluated.5 However, these treatments have had no impact on the mortality stemming from the disease.5 The lack of success with these new interventions is probably multifactorial.6 One possible explanation is that the appropriate patient population had not been enrolled for study.7 In this regard, it is also probably unrealistic to hope that a single treatment will modify the evolution of all ARDS patients who represent a heterogeneous population with very different severities of lung injury. Thus, it is unlikely that the efficacious treatment of patients with mild lung injury will be as efficient in patients with severe lung injury.

Most of the treatments tested recently were targeted to control the inflammatory response.5 Although the development of lung injury is mainly dependent on aggression of endothelial cells by inflammatory cells,8 its severity and recovery also depend on epithelial cell function.9 In fact, the predominant pathological finding in acute lung injury is diffuse alveolar epithelial damage.10 11 Furthermore, physiologically it has been shown that the structure and function of the alveolar epithelium are important determinants of lung injury.12Finally, the alveolar epithelium is also the site of alveolar fluid reabsorption and plays a major role in the development of lung fibrosis associated with ARDS.13-15 Treatments aimed at improving epithelial function might therefore become one of the key elements to accelerate recovery and decrease the mortality of patients with ARDS.

In this review we will emphasise the importance of modulating two …
A5.11 Detection of ACPA Producing B-Cells by a Citrulline Peptide Panel
Authors: Eszter Szarka, Krisztina Huber, Judit Pozsgay, Fruzsina Babos, Tamás Gáti, Anna Magyar, Ferenc Hudecz, Bernadette Rojkovich, György Nagy, Gabriella Sármay
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Anti-citrullinated protein/peptide antibodies (ACPAs) are the most sensitive and specific serological markers of RA. To identify the optimal epitopes that detect different subgroups of RA patients with high sensitivity and specificity, we have investigated citrulline and arginine containing peptides derived from filaggrin, collagen or vimentin. We have identified a citrulline-containing peptide panel that was recognised by RA sera with high specificity. Our aim was to compare this peptide panel with the conventionally used serological assays and to detect peptide-specific ACPA producing B-cells in in vitro cultures<i>.</i> <h3>Materials and Methods</h3> Previously selected citrulline- and arginine-containing filaggrin, vimentin and collagen peptide epitopes were investigated. We compared the recognition of these peptides by RA and control sera using indirect ELISA. B-cells were purified from peripheral blood by negative selection, IgG production was stimulated by B-cell activators (R848 and recombinant human IL-2) provided with the human ELISPOT kit. Antibody producing cells were enumerated after 4 days culture by using peptide-specific ELISPOT assay. <h3>Results</h3> Sera samples from 247 RA and 148 age-matched (57 ± 14 years) healthy controls were collected. The citrulline peptide panel detected approximately 80% of RA patients, including 20% of seronegative/CCP negative patients as well. Individual peptides detected different subgroups of RA patients. The more peptides recognised by a particular RA serum sample, the more severe the disease of the patient was. In vitro cultured B-cells from selected RA patients synthesised multiple citrulline-containing peptide-specific antibodies after polyclonal stimulation, while B-cells from healthy blood donors did not. <h3>Conclusions</h3> The citrulline peptide panel can detect 20% of ACPA negative RA patients thus may have a prognostic value. Furthermore, the panel is suitable to detect citrulline peptidespecific antibody producing cells, thus enables us to study ACPA producing B-cells of RA patients.
SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE
Authors: Harvey Cantor, Richard Asofsky, Norman Talal
Journal: The Journal of Experimental Medicine (1970)

The ability of spleen cells from young (3 month) and old (1 yr) NZB mice to induce GVH reactions in newborn C57BL/6N mice was compared quantitatively using the Simonsen spleen assay. Young NZB cells were five times more reactive than cells from older mice. The minimum number of cells producing detectable reactions was 2 x 10(6) for the young and 10 x 10(6) for the old. Young and old cells combined and injected together produced GVH reactions quantitatively similar to those obtained with inocula composed of young cells alone. Mixtures of two cell populations producing no detectable reactions when injected separately into different recipients (1 x 10(6) young cells and 4 x 10(6) old cells) produced reactions approximately equal to those obtained with 5 x 10(6) young cells. As few as 0.25 x 10(6) young cells were sufficient to effect a reaction when combined with 4.75 x 10(6) old unreactive cells. Viability of both cell populations was essential for GVH reactivity. This evidence of synergy in GVH reactions indicates that old NZB spleen cells can be rendered immunologically more reactive in the presence of a normally reactive population.
Peter Alec James Ball
Authors: Jenifer Ball, Chris Hudson
Journal: BMJ (2006)

​FormerFormer consultant gastroenterologist Middlesex Hospital and natural historian (b 1928; q Cambridge/Middlesex Hospital, London, 1952; MA, MD, FRCP), died from a stroke on 12 February 2006.




Figure 1




Peter Ball was seconded in 1961 to University College, Ibadan, Nigeria, where he completed his doctorate in parasitology. From 1964 he returned to the Middlesex Hospital as consultant gastroenterologist and general physician. He was postgraduate subdean, researched into nematodes at the Zoological Society, sat on the editorial committees of the British National Formulary and the Prescribers' Journal, and was assistant registrar and later censor of the Royal College of Physicians. In 1985 he became assistant director, the Wellcome Trust. He later ran a project on undergraduate medical education at the King's Fund. Predeceased in 1991 by his wife, Anne, and a son in infancy, he leaves five children and six grandchildren.