tbuckley/cabot-search huggingface dataset:
Abstract 329: A mouse model of epithelial ovarian cancer with defined oncogenic drivers.
Authors: Hasmik Agadjanian, Dong-Joo Cheon, Elena Diaz, Anna Laury, Carl Miller, Beth Karlan, Sandra Orsulic, Christine Walsh
Journal: Cancer Research (2013)

Abstract Epithelial ovarian cancers (EOC) represent the gynecologic malignancy with the highest mortality rate. The Cancer Genome Atlas demonstrated a high degree of genetic heterogeneity among the papillary serous (PS) tumors, the most lethal of the EOC subtypes. Aside from almost universal mutation in TP53, there was a low prevalence of recurrent mutations in other genes, presenting a challenge to the development of targeted therapeutics against this aggressive tumor type. We are developing a mouse model of EOC by introducing defined genetic alterations to mouse ovarian surface epithelial (MOSE) cells. We had a particular interest in developing a cyclin E amplified tumor model, as CCNE1 amplification is found in 20% of human EOC tumors, making this one of the most prevalent PS EOC subtypes. We infected MOSE cells from p53-/- mice with different combinations of oncogenes encoded in retroviral vectors including CCNE1, myc and H-RAS. MOSE cells were infected with one or two oncogenes, passaged and injected into the peritoneal cavity of nude mice. Myc-HRAS caused the rapid development of hemorrhagic ascites and intraperitoneal carcinomatosis in 5 of 5 mice by day 18. HRAS alone and HRAS-CCNE1 both caused intraperitoneal and omental tumors to develop with clear ascites by day 35 in 5 of 5 mice. Myc caused bloating due to the development of frank hemoperitoneum in all 5 mice between days 101 and 150. Only 4 of the 5 mice had small volume intraperitoneal tumors. Myc-CCNE1 similarly caused bloating due to ascites in 2 mice and hemoperitoneum in 2 mice. Three of these four mice had small volume intraperitoneal tumors. One mouse has not developed any phenotype by 150 days. CCNE1 alone has not caused tumor formation in any of 5 mice by day 150. Histology of the Myc-HRAS, HRAS, HRAS-CCNE1, and Myc tumors were all consistent with high-grade undifferentiated carcinoma. Tumor cells generated in the Myc-HRAS, HRAS and HRAS-CCNE1 experiments were capable of causing intraperitoneal tumor development in immunocompetent C57BL/6 mice by day 17, 29 and 54 respectively. Taken together, our data demonstrate a reproducible mouse model for the development of high-grade epithelial ovarian carcinomas with defined genetic alterations that are capable of study in both immunodeficient and immunocompetent mice. Tumor phenotypes varied based on the combination of activated oncogenes. Citation Format: Hasmik Agadjanian, Dong-Joo Cheon, Elena Diaz, Anna Laury, Carl Miller, Beth Karlan, Sandra Orsulic, Christine Walsh. A mouse model of epithelial ovarian cancer with defined oncogenic drivers. [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 329. doi:10.1158/1538-7445.AM2013-329
Dendritic cells are required for effective cross-presentation in the murine liver
Authors: George Plitas, Bryan M. Burt, Jennifer A. Stableford, Hoang M. Nguyen, Alexander P. Welles, Ronald P. DeMatteo
Journal: Hepatology (2008)

The liver harbors a diversity of cell types that have been reported to stimulate T cells. Although most hepatic dendritic cells are immature, a small population of CD11chigh conventional dendritic cells (cDCs) exists that expresses high levels of costimulatory molecules. We sought to determine the relative contribution of cDCs to cross-presentation by the liver. In vitro, liver nonparenchymal cells (NPCs) depleted of cDCs induced only minimal proliferation and activation of antigen-specific CD8+ T cells when loaded with soluble protein antigen. Using a transgenic mouse with the CD11c promoter driving expression of the human diphtheria toxin receptor, we found that selective depletion of cDCs in vivo reduced the number and activation of antigen-specific CD8+ T cells in the liver after intravenous administration of soluble protein antigen. Adoptive transfer of DCs, but not CD40 stimulation, restored the hepatic T-cell response. Conclusion: Our findings indicate that the ability of the liver to effectively cross-present soluble protein to antigen-specific CD8+ T cells depends primarily on cDCs. Despite costimulation, other resident liver antigen-presenting cells cannot compensate for the absence of cDCs. (HEPATOLOGY 2008.)
Action is still needed to stem heterosexual transmission of HIV in Africa
Authors: D. M G Bowley
Journal: BMJ (2002)

EDITOR—The startling statistic, reported by Eleni Papadopulos-Eleopulos et al,1 that it would take up to 222 years to achieve a 95% probability of becoming infected with HIV during heterosexual intercourse, will be small consolation to the people of southern Africa.

Heterosexual transmission of HIV-1 depends on the infectiousness of the index case and the susceptibility of the uninfected partner. Infectivity seems to vary during the course of illness and is not constant between individuals,2 each log10 increment of …
FDG Uptake in Tumor Thrombus in Inferior Vena Cava From Rectal Cancer on Positron Emission Tomography
Authors: Pramod Gupta, Elissa L. Kramer, Fabio Ponzo
Journal: Clinical Nuclear Medicine (2005)

A 74-year-old woman with a history of rectal carcinoma underwent whole body combined positron emission tomography/computed tomography (PET/CT) scanning for staging. Diffuse intense FDG uptake was seen in the distended infrarenal inferior vena cava (IVC) extending to the bilateral common iliac and left external as well as internal iliac veins. Heterogeneous hyperdense material was seen on the corresponding CT scan, suggesting tumor thrombus. Tumor thrombus shows increased FDG uptake resulting from the increased glycolytic rate in malignant cells.
Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis
Authors: Mayte Suárez-Fariñas, Nikhil Dhingra, Julia Gittler, Avner Shemer, Irma Cardinale, Cristina de Guzman Strong, James G. Krueger, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2013)
Resignations with Reluctance
Authors: J. H. Bradshaw-Smith, A. T. H. Glanvill, R. V. H. Jones, W. H. McBay, G. G. Ward, R. S. K. Essame, C. J. Glanvill, K. D. E. Lawrey, J. F. N. Sidebotham
Journal: BMJ (1965)
PROFESSIONALIZATION IN PUBLIC HEALTH SERVICE
Authors: JOHN A. FERRELL
Journal: JAMA (1933)

The term "professionalization" as employed in this discussion refers to the establishment of suitable educational and professional standards for public health personnel. In the older professions of medicine, law and dentistry, it became necessary to protect the public against unqualified practitioners, many of whom held diplomas. This was done through the establishment of qualifying boards. Consideration of the situation in respect to public health raises a number of questions, a few of which are as follows: Is public health service a specialty of medicine? Is it so distinct from medicine as to warrant its being regarded as a new and separate profession? Has sufficient progress been made to warrant the adoption of qualification standards for the personnel? Should the examinations required of health officers be open only to physicians? Should suitable examinations be offered and certificates awarded to personnel necessary in health organizations, other than the health officers, such as
Antibodies to cellular antigens in Greek patients with autoimmune rheumatic diseases: anti-Ro(SSA) antibody a possible marker of penicillamine-D intolerance.
Authors: H.M Moutsopoulos, H Giotaki, P.J Maddison, A.C Mavridis, A.A Drosos, F.N Skopouli
Journal: Annals of the Rheumatic Diseases (1984)

One hundred and twenty-four sera from Greek patients with autoimmune rheumatic diseases (29 with systemic lupus erythematosus (SLE), 24 with scleroderma, 11 with primary Sjögren's syndrome (SS), and 60 with rheumatoid arthritis (RA) were tested for antibodies to nRNP, Sm, Scl-70, Ro(SSA), and La(SSB) cellular antigens. The incidence of these antibodies in the different groups of patients examined, did not differ overall from that described previously. It was noted, however, that antibodies to Sm were very infrequently found in Greek patients with SLE and anti-Ro positive patients with SLE did not have the clinical manifestations described by other workers. Finally, it was found that anti-Ro positive patients with RA experienced a high frequency of side effects from penicillamine-D. The significance of these findings is discussed.
Estrogen augments incorporation of bone marrow-derived endothelial progenitor cells into sites of myocardial neovascularization
Authors: Atsushi Iwakura, Corinne Luedemann, Atsuhiko Kawamoto, Shubha Shastry, Takayuki Asahara, Douglas W. Losordo
Journal: Journal of the American College of Cardiology (2003)
PNEUMOTHORAX IN PNEUMONIA
Authors: Thomas J. West
Journal: JAMA (1934)

To the Editor:—  A number of Eastern hospitals have lately reported experimentation with pneumothorax in pneumonia. In 1915 and 1916 I had some correspondence with the late Dr. John B. Murphy when he was pioneering in the pneumothorax treatment of tuberculosis.  I made the suggestion to him at that time that the same treatment be applied in early unilateral lobar pneumonia. The following reasons were offered:  First: Rest to the involved lung.  Second: Relief of pleural pains, minus opiates. Under date of April 15, 1916, Dr. Murphy wrote me:  I have referred it to my associate, Dr. Kreuscher, who has charge of the pneumothorax department of my clinic. I have given instructions that it be done as soon as possible and will be pleased to report to you. Thanking you for the suggestion, and with best wishes, I am, Yours very truly, J. B. Murphy.  In view of the fact
Abnormal skeletal muscle bioenergetics during exercise in patients with heart failure: role of reduced muscle blood flow.
Authors: D H Wiener, L I Fink, J Maris, R A Jones, B Chance, J R Wilson
Journal: Circulation (1986)

Using phosphorous nuclear magnetic resonance, we have previously demonstrated that patients with heart failure often exhibit abnormal forearm muscle metabolism during forearm exercise. To determine if this altered metabolism is due to reduced muscle flow, we measured forearm blood flow with plethysmography and forearm muscle inorganic phosphate (Pi), phosphocreatine (PCr), and pH with 31P nuclear magnetic resonance spectroscopy at rest and during mild forearm exercise (0.2, 0.4, and 0.6 W) in 21 men with heart failure and in 12 age-matched normal male subjects. The Pi/PCr ratio was correlated with power output and the slope of this relationship was used as an index of forearm metabolism. At rest, both groups had similar Pi/PCr ratios (normal subjects 0.11 +/- 0.05; patients with heart failure 0.11 +/- 0.03; p = NS) and forearm blood flows (normal subjects 2.9 +/- 1.4 ml/min/100 ml; patients with heart failure 2.6 +/- 1.2 ml/min/100 ml; p = NS). In both groups, exercise resulted in a progressive increase in both Pi/PCr and forearm blood flow as power output increased. However, the patients exhibited a steeper slope of the Pi/PCr-to-power output relationship than did the normal subjects (normal subjects 1.4 +/- 0.6 Pi/PCr U/W; patients with heart failure 3.0 +/- 2.4 Pi/PCr U/W; p less than .03). In contrast, forearm blood flow was similar in both groups during exercise (at 0.2 W, 6.3 +/- 3.3 and 6.8 +/- 3.2 ml/min/100 ml in normal subjects and patients with heart failure, respectively; at 0.4 W, 8.7 +/- 6.5 and 8.3 +/- 3.3; at 0.6 W, 12.8 +/- 7.9 and 12.0 +/- 4.6; all p = NS). Nine of the 21 patients with heart failure had slopes of the Pi/PCr-to-power output relationship above the normal range. These nine patients also had forearm blood flows comparable to flows observed in the normal subjects. These data indicate that forearm muscle metabolism during forearm exercise is altered in a subpopulation of patients with heart failure. This metabolic alteration does not appear to be due to decreased muscle blood flow, suggesting that other mechanisms, such as alterations in mitochondrial population or substrate utilization, may be responsible.
Morphine and biliary pain revisited
Authors: E A SHAFFER
Journal: Gut (2000)

See article on page 838 

Pain in the biliary tract is assumed to originate from either an obstructive event (the gall bladder contracting on a closed cystic duct, blocked by a gall stone) or inflammation (cholecystitis). Neither situation should be present after the gall bladder is extricated yet pain may persist.

The “post cholecystectomy syndrome” is a poorly defined entity which includes many symptoms that range from the trivial (mild dyspepsia) to severe attacks of abdominal pain and jaundice.1 Depending on the original indication for surgery, 20–50% of patients after cholecystectomy continue to have a variety of non-specific abdominal symptoms such as flatulence and dyspepsia.2-4 True biliary type pain occurs as a relatively small percentage (14%) of symptoms which follow cholecystectomy.5 From a different perspective, such pain following cholecystectomy was a complaint in only 0.6% of men and 2.3% of women in a household survey.6 When symptoms persist following cholecystectomy and no organic basis is evident (from a stricture, retained common duct stone, pancreatitis, tumour, or congenital anomaly) by default the basis becomes “functional”. With the gall bladder gone and the bile ducts (which lack a smooth muscle layer) acting as a simple conduit, the sphincter of Oddi (SO) becomes the prime suspect for the pain through spasm or biliary obstruction. The sphincter, strategically located at the junction of the biliary tract, pancreas, and duodenum, is like a …
Reversibility of Airflow Obstruction by Hypoglossus Nerve Stimulation in Anesthetized Rabbits
Authors: François Bellemare, Matteo Pecchiari, Monica Bandini, Mohamad Sawan, Edgardo D'Angelo
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Anesthesia-induced uncoupling of upper airway dilating and inspiratory pump muscles activation may cause inspiratory flow limitation, thereby mimicking obstructive sleep apnea/hypopnea.Determine whether inspiratory flow limitation occurs in spontaneously breathing anesthetized rabbits and whether this can be reversed by direct hypoglossal nerve stimulation and by the application of continuous positive airway pressure.Ten New Zealand White rabbits were anesthetized, instrumented, and studied supine while breathing spontaneously at ambient pressure or during the application of positive or negative airway pressure. Under each of these conditions, the effect of unilateral or bilateral hypoglossal nerve stimulation was investigated.Inspiratory flow and tidal volume were measured together with esophageal pressure and the electromyographic activity of diaphragm, alae nasi, and genioglossus muscles.Anesthesia caused a marked increase in inspiratory resistance, snoring, and in eight rabbits, inspiratory flow limitation. Hypoglossus nerve stimulation was as effective as continuous positive airway pressure in reversing inspiratory flow limitation and snoring. Its effectiveness increased progressively as airway opening pressure was lowered, reached a maximum at -5 cm H2O, but declined markedly at lower pressures. With negative airway opening pressure, airway collapse eventually occurred during inspiration that could be prevented by hypoglossus nerve stimulation. The recruitment characteristics of hypoglossus nerve fibers was steep, and significant upper airway dilating effects already obtained with stimulus intensities 36 to 60% of maximum.This study supports hypoglossus nerve stimulation as a treatment option for obstructive sleep apnea.
Abnormality of Phospholipids in Red Cells of Patients with Paroxysmal Nocturnal Haemoglobinuria
Authors: I. M. Harris, T. A. J. Prankerd, M. P. Westerman
Journal: BMJ (1957)

The key to the early warning of a deteriorating clinical situation lies in the change in parameters rather than in their absolute value. This not only colours the choice of sensor, but also affects the design of the discriminators between the sensors and the logic circuits. While the sensors and logic are clearly the most important parts of the equipment, it is probably the presentation of information which will in the end decide the extent to which it is used by nursing staff, and every care must be taken to ensure, not only that false alarms are minimized, but that genuine alarms do not cause unnecessary agitation of the patient.
Truncated p95erbB2 Isoforms Are Capable of Transforming Human Mammary Epithelial Cells.
Authors: T. Ward, E. Iorns, M. Gallas, M. Lippman, R. Landgraf, M. Pegram
Journal: Cancer Research (2009)

Abstract Background:Objective clinical response to trastuzumab monotherapy in erbB2-amplified first line metastatic breast cancer is 34% (Vogel, et al., JCO 20: 719-26, 2002). Amongst patients who respond, most develop resistance (defined by disease progression on trastuzumab). One proposed mechanism of trastuzumab resistance is proteolytic cleavage of erbB2 receptor from its full-length (p185) form into truncated, constitutively active p95. Increased expression of p95erbB2 correlates with increased nodal involvement and poor clinical outcome. Because p95erbB2 lacks the trastuzumab binding epitope, expression may designate patients who would be suitable for treatment with erbB2 kinase inhibitors.Materials and Methods:Recombinant p185erbB2 and p95erbB2 constructs were stably expressed in several cell types via retroviral vector. Additionally, an intracellular form of p95erbB2 that arises via alternative translation and an intracellular p95erbB2 construct containing two copies of a nuclear localization sequence were also expressed. Expression and proper subcellular localization of constructs were confirmed by cell fractionation, western blot analysis and confocal microscopy. Transformation of human mammary epithelial (HMEC) and NIH3T3 cells by p185erbB2 and p95erbB2 isoforms was evaluated by anchorage independent growth using a quantitative fluorescent soft agar assay, and effects on migration and invasion of these cells were investigated by wound-healing and transwell assays. Cells transfected with oncogenic Ras or empty vector were used as positive and negative controls in these experiments.Results and Discussion:Recombinant p185erbB2 and p95erbB2 constructs were stably expressed in HMEC and NIH3T3 cells, and were correctly directed to the cell membrane; nuclear targeted intracellular p95erbB2 was correctly localized to the cell nucleus. Both p185 erbB2 and membrane-bound truncated p95erbB2 were sufficient to transform HMEC cells as compared to empty vector control transfected cells [mean fluorescence intensity empty vector control 2480 ± 464 (1 standard deviation); mean fluorescence intensity p185erbB2 9208 ± 2528, p= 0.0106; mean fluorescence intensity p95erbB2 6615 ± 1588, p= 0.0124)] as was the positive control oncogenic Ras (mean fluorescence intensity 4350 ± 433, p=0.0069). Interestingly, nuclear-targeted p95erbB2 was also sufficient to transform HMEC cells (mean fluorescence intensity 6492 ± 818, p=0.0018). These data support the hypothesis that truncated p95erbB2 species may be major pathogenic drivers in erbB2-amplified cancers. P95erbB2 therefore represents an attractive target for diagnosis and treatment of erbB2+ breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3136.
Effects of Patient-Directed Music Intervention on Anxiety and Sedative Exposure in Critically Ill Patients Receiving Mechanical Ventilatory Support
Authors: Linda L. Chlan, Craig R. Weinert, Annie Heiderscheit, Mary Fran Tracy, Debra J. Skaar, Jill L. Guttormson, Kay Savik
Journal: JAMA (2013)

<h3>Importance</h3>Alternatives to sedative medications, such as music, may alleviate the anxiety associated with ventilatory support.<h3>Objective</h3>To test whether listening to self-initiated patient-directed music (PDM) can reduce anxiety and sedative exposure during ventilatory support in critically ill patients.<h3>Design, Setting, and Patients</h3>Randomized clinical trial that enrolled 373 patients from 12 intensive care units (ICUs) at 5 hospitals in the Minneapolis-St Paul, Minnesota, area receiving acute mechanical ventilatory support for respiratory failure between September 2006 and March 2011. Of the patients included in the study, 86% were white, 52% were female, and the mean (SD) age was 59 (14) years. The patients had a mean (SD) Acute Physiology, Age and Chronic Health Evaluation III score of 63 (21.6) and a mean (SD) of 5.7 (6.4) study days.<h3>Interventions</h3>Self-initiated PDM (n = 126) with preferred selections tailored by a music therapist whenever desired while receiving ventilatory support, self-initiated use of noise-canceling headphones (NCH; n = 122), or usual care (n = 125).<h3>Main Outcomes and Measures</h3>Daily assessments of anxiety (on 100-mm visual analog scale) and 2 aggregate measures of sedative exposure (intensity and frequency).<h3>Results</h3>Patients in the PDM group listened to music for a mean (SD) of 79.8 (126) (median [range], 12 [0-796]) minutes/day. Patients in the NCH group wore the noise-abating headphones for a mean (SD) of 34.0 (89.6) (median [range], 0 [0-916]) minutes/day. The mixed-models analysis showed that at any time point, patients in the PDM group had an anxiety score that was 19.5 points lower (95% CI, −32.2 to −6.8) than patients in the usual care group (P = .003). By the fifth study day, anxiety was reduced by 36.5% in PDM patients. The treatment × time interaction showed that PDM significantly reduced both measures of sedative exposure. Compared with usual care, the PDM group had reduced sedation intensity by −0.18 (95% CI, −0.36 to −0.004) points/day (P = .05) and had reduced frequency by −0.21 (95% CI, −0.37 to −0.05) points/day (P = .01). The PDM group had reduced sedation frequency by −0.18 (95% CI, −0.36 to −0.004) points/day vs the NCH group (P = .04). By the fifth study day, the PDM patients received 2 fewer sedative doses (reduction of 38%) and had a reduction of 36% in sedation intensity.<h3>Conclusions and Relevance</h3>Among ICU patients receiving acute ventilatory support for respiratory failure, PDM resulted in greater reduction in anxiety compared with usual care, but not compared with NCH. Concurrently, PDM resulted in greater reduction in sedation frequency compared with usual care or NCH, and greater reduction in sedation intensity compared with usual care, but not compared with NCH.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00440700