tbuckley/cabot-search huggingface dataset:
Abstract 1072: The FGF18/FGFR4 amplicon: Novel therapeutic biomarkers for ovarian cancer
Authors: Wei Wei, Gayatry Mohapatra, Michael J. Birrer
Journal: Cancer Research (2012)

Abstract Epithelial ovarian cancer is the fifth leading cause of cancer-related death among women and has the highest case-fatality rate among gynecologic cancers. High throughput genomic technologies have been instrumental in identifying new biomarkers and potential novel therapeutic targets for ovarian cancer. However, comprehensive functional validation studies on both the biological and clinical levels are needed to better understand the mechanistic basis for these biomarkers and realize their clinical significance and application. Fibroblast growth factor 18 (FGF18) has been recently identified as an aberrantly expressed gene within an expression signature predicting poor rate of survival in patients with advanced stage serous ovarian cancers. In addition, genomic amplification of both FGF18 and FGFR4 has been shown to predict for poor overall survival among women with advanced stage high grade serous ovarian cancers. siRNA mediated knock-down of FGFR4 abolishes FGF18 induced phosphorylation of FRS2 and ERK1/2 in ovarian cancer cells, indicating the FGF18 signaling is at least partially conferred by FGFR4 in ovarian cancer cells. However, the exact role of FGF18/FGFR4 in the clinicopathologic properties of ovarian cancer has not been determined. Preliminary studies by ectopic FGF18 overexpression or recombinant FGF18 treatment demonstrate that FGF18 promotes the in vitro migration and invasion of both ovarian cancer cells and endothelial cells. In SCID mice xenograft models, FGF18 expression in ovarian cancer cells results in increased tumor formation. Microarray analysis identified up-regulation of a large number of proinflammatory cytokines by FGF18 which may mediate the increases in angiogenesis and infiltration of macrophages seen in FGF18 expressing xenografts. Pathway analysis further demonstrated participation of NF-κB signaling in FGF18 mediated cytokine production. Conversely, knock-down of FGF18 in ovarian cancer cells reduces the in vitro migration; inhibits the production of cytokines and impairs the in vivo tumorigenicity in SCID mice xenograft model. Taken together, FGF18/FGFR4 axis may play an important role in ovarian cancer pathogenesis and may serve as a novel therapeutic target. 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 1072. doi:1538-7445.AM2012-1072
Altered Autonomic Function and Reduced Arousability in Apparent Life-Threatening Event Infants with Obstructive Sleep Apnea
Authors: Carmel Harrington, Turkka Kirjavainen, Arthur Teng, Colin E. Sullivan
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The aim of this study was to examine cardiorespiratory control in infants presenting with an apparent life-threatening event (ALTE). We performed six to eight 45 ° head-up tilts in 10 ALTE infants (age, 14 ± 3 weeks) and 12 age-matched control subjects during slow wave sleep and rapid eye movement sleep (REM). All infants underwent full overnight polygraphic sleep recordings with noninvasive measurement of beat-to-beat blood pressure. All control infants had normal sleep breathing. In contrast, 5 of the 10 ALTE infants had more than two obstructive apneas per hour of sleep, with short hypoxic episodes (obstructive sleep apnea [OSA]). In slow wave sleep, in response to the tilt, the ALTE infants with OSA showed a reduced heart rate response, and three of the five showed a marked postural hypotension. The ALTE infants with OSA also had altered heart rate and blood pressure variability and an increased arousal threshold in REM (p = 0.0002). By contrast, those ALTE infants with normal sleep breathing had cardiovascular and arousal responses similar to those of the control infants. We conclude that a number of ALTE infants with OSA have abnormal cardiovascular autonomic control that, combined with their decreased arousability in REM, may provide an explanation for the ALTE episodes.
Activation of large conductance potassium channels inhibits the afferent and efferent function of airway sensory nerves in the guinea pig.
Authors: A J Fox, P J Barnes, P Venkatesan, M G Belvisi
Journal: Journal of Clinical Investigation (1997)

Sensory nerves play an important role in airway disease by mediating central reflexes such as cough, and local axon reflexes resulting in the peripheral release of neuropeptides. We have tested whether the benzimidazolone compound, NS1619, an opener of large conductance calcium-activated potassium (BK Ca) channels, inhibits the activity of sensory fibers, and central and local airway reflexes in guinea pig airways. In in vitro single fiber recording experiments, NS1619 applied to identified receptive fields in the trachea inhibited the firing of A(delta)-fibers evoked by hypertonic saline and distilled water, and bradykinin-evoked firing of C-fibers. Electrically evoked nonadrenergic noncholinergic contractions of isolated bronchi mediated by the release of neurokinin A (NKA) from C-fibers, but not those elicited by exogenous NKA, were inhibited by NS1619. These effects of NS1619 were prevented by iberiotoxin, a selective blocker of BK Ca channels. In conscious guinea pigs, cough evoked by aerosolized citric acid was also inhibited by NS1619. These data show that BK Ca channel activation inhibits sensory nerve activity, resulting in a reduction of both afferent and efferent function. BK Ca channel openers may therefore be of potential benefit in reducing neurogenic inflammation and central reflexes seen during inflammatory conditions of the airways, and may represent a new class of antitussive drug.
An inhibitor of nitric oxide synthase does not increase contraction or β-adrenoceptor sensitivity of ventricular myocytes from failing human heart
Authors: S Harding
Journal: Cardiovascular Research (1998)

Objective: Nitric oxide (NO) has been implicated in the depression of cardiac function in human heart failure. Some reports have identified iNOS (inducible nitric oxide synthase) within the myocyte component of the failing human heart, and NO is known to decrease the contraction amplitude of isolated ventricular myocytes. We have treated myocytes from failing human ventricle with a NOS inhibitor, NG-monomethyl-l-arginine (L-NMMA), in an attempt to restore contractile function. Methods and Results: Myocytes were isolated from failing and non-failing human ventricles and their contraction amplitude was measured during superfusion (32°C, 1–2 mmol/l Ca2+) and electrical stimulation (0.1–2 Hz). The contraction amplitude of myocytes from failing hearts was depressed in a frequency-dependent manner. At 1 Hz, the contraction amplitude of cells from non-failing heart was 4.70±0.53% cell shortening (mean±SEM, n=13 subjects), compared with 2.18±0.27% (P<0.01, 11 patients) from patients with ischaemic heart disease (IHD) or 2.56±0.74% (P<0.02, six patients) with dilated cardiomyopathy (DCM). Superfusion with 0.1 mmol/l L-NMMA did not increase contraction amplitude in myocytes from failing heart at either 0.2 Hz (n=11) or 1 Hz (n=7). Responses to β-adrenoceptor stimulation were reduced in myocytes from failing human heart, with contraction amplitude in maximum isoprenaline 0.47±0.11 of that in high Ca2+ in the same cell (n=6), compared to 0.99±0.07 in non-failing heart (n=14, P<0.01). The presence of 0.1 mmol/l L-NMMA did not increase the isoprenaline/Ca2+ ratio in myocytes from failing heart (0.40±0.09, P=NS). Conclusion: These results do not suggest a functional role for tonic NO production in the frequency-dependent depression of contraction or β-adrenoceptor desensitisation in myocytes from failing human ventricle.
Role of Early Developmental Factors in Susceptibility to Disease
Authors: George N. Christodoulou, Thalia G. Dragonas
Journal: Psychotherapy and Psychosomatics (1992)

Early developmental factors implicated in subsequent infant and child development are presented. The orientation adopted emphasizes both the interplay between constitutional and environmental factors and the mutual interaction between the child and its environment. The present paper concentrates on pre- and perinatal factors and maternal psychopathology affecting mainly the early mother-child interaction and, in turn, child developmental outcome.
Concomitant Vascular Reconstruction During Pancreatectomy for Malignant Disease
Authors: Mathias Worni, Anthony W. Castleberry, Bryan M. Clary, Beat Gloor, Elias Carvalho, Danny O. Jacobs, Ricardo Pietrobon, John E. Scarborough, Rebekah R. White
Journal: JAMA Surgery (2012)

To assess trends in the frequency of concomitant vascular reconstructions (VRs) from 2000 through 2009 among patients who underwent pancreatectomy, as well as to compare the short-term outcomes between patients who underwent pancreatic resection with and without VR.Single-center series have been conducted to evaluate the short-term and long-term outcomes of VR during pancreatic resection. However, its effectiveness from a population-based perspective is still unknown. Unadjusted, multivariable, and propensity score-adjusted generalized linear models were performed.Nationwide Inpatient Sample from 2000 through 2009.A total of 10,206 patients were involved.Incidence of VR during pancreatic resection, perioperative in-hospital complications, and length of hospital stay.Overall, 10,206 patients were included in this analysis. Of these, 412 patients (4.0%) underwent VR, with the rate increasing from 0.7% in 2000 to 6.0% in 2009 (P < .001). Patients who underwent pancreatic resection with VR were at a higher risk for intraoperative (propensity score-adjusted odds ratio, 1.94; P = .001) and postoperative (propensity score-adjusted odds ratio, 1.36; P = .008) complications, while the mortality and median length of hospital stay were similar to those of patients without VR. Among the 25% of hospitals with the highest surgical volume, patients who underwent pancreatic surgery with VR had significantly higher rates of postoperative complications and mortality than patients without VR.The frequency of VR during pancreatic surgery is increasing in the United States. In contrast with most single-center analyses, this population-based study demonstrated that patients who underwent VR during pancreatic surgery had higher rates of adverse postoperative outcomes than their counterparts who underwent pancreatic resection only. Prospective studies incorporating long-term outcomes are warranted to further define which patients benefit from VR.
Covert Drug Abuse Among Voluntary Hospitalized Psychiatric Patients
Authors: Arnold G. Blumberg
Journal: JAMA (1971)

A survey of 332 young psychiatric patients, by means of repeated urinary chromatographic analyses, revealed that at least 60% of these patients employed abusable drugs while hospitalized. Barbiturates were detected most frequently, and addiction did not occur among patients who remained in the hospital. The high incidence of drug abuse in hospitalized patients must be considered in the light of alterations of psychiatric states and in the interpretation of treatment results. The chromatographic screening of the urine of hospitalized patients for nonprescribed drugs is recommended.
The Factor of Disease in the World Food Problems
Authors: Herbert Pollack
Journal: JAMA (1970)

The paramount world health problems appear to be those of nutrition and infectious disease and their interrelationships in a self-reinforcing cause-effect cycle. Three of the major disease entities, dysentery, malaria, and tuberculosis of the respiratory tract are evaluated in terms of caloric energy losses resulting from both increased metabolism in disease and lost productivity. In terms of annual caloric cost of disease, respiratory tuberculosis is clearly the most wasteful disease entity per case; while malaria, because of its high incidence levels, remains the more significant world health problem. Using 1965 disease incidence data even a conservatively based first approximation indicates that the value of present nutritional losses occasioned by a population's disease burden is not trivial. There is potential significance of such calculations to national development planners.
Prescribing patient information leaflets may be better than prescribing drugs
Authors: T Kenny, R Wilson, I N Purves
Journal: BMJ (1998)

EDITOR—Greenhalgh and Gill highlight the “disparate factors on the decision to prescribe,” but they offer little advice in terms of strategies to resist the pressure to prescribe.1 They describe a study in which 22% of prescriptions were thought to be not strictly indicated by the prescribing general practitioner.2 Giving an information leaflet on some of these …
THE PRODUCTION BY STAPHYLOCOCCI OF A SUBSTANCE CAUSING FOOD POISONING
Authors: EDWIN OAKES JORDAN
Journal: JAMA (1930)

A recent outbreak of food poisoning in Chicago was traced by Dack<sup>1</sup>to the eating of a Christmas cake. Samples of the incriminated food were brought to the bacteriology laboratory of the University of Chicago and subjected to bacterial examination. A yellow staphylococcus present in considerable abundance in the cake substance was among the organisms isolated and studied. This staphylococcus apparently produced a toxic substance in broth, as shown by the effect of the sterile filtrate, which when swallowed by a human volunteer gave rise to nausea, diarrhea and prostration of the same character as that observed in the original outbreak.<sup>1</sup> One similar instance has been previously recorded: Barber<sup>2</sup>in the Philippines in 1914 reported several cases of milk poisoning due to a strain of<i>Staphylococcus albus</i>occurring in the udder of an apparently healthy cow. Fresh milk containing the staphylococcus did not apparently produce illness, but
The Pre-S region determines the intracellular localization and appearance of hepatitis B virus
Authors: Thomas C. Bock, Hans L. Tillmann, Michael P. Manns, Christian Trautwein
Journal: Hepatology (1999)

The functional role of the hepatitis B virus (HBV) pre-S region for assembly and appearance of the virus is not completely understood. In this study, 3 natural-occurring mutants were investigated. Three mutants of the pre-S region-a point mutation in the CCAAT box (MUT1), a 6-bp deletion (MUT2) 3' of the CCAAT box, and a 153-bp deletion (MUT3) in the preS2 domain-were cloned alone or in combinations in replication-competent HBV plasmids and transfected in hepatoma cells. The impact on HBV assembly and appearance was studied by Northern Blot, primer extension analysis, immunofluorescence studies, enzyme-linked immunosorbent assay, and electron microscopy. An inversed ratio of pre-S/S mRNA transcripts compared with wild-type (wt) HBV was found when either MUT1 or -2 were included into the plasmid. Intracellular localization with both mutants showed retention of large S-protein in the endoplasmic reticulum and nuclear accumulation of core protein. The extracellular amount of S-protein was reduced with MUT1 and -2 or combinations in which 1 of the mutants was included. However, the extracellular appearance of viral products was comparable with wtHBV. In contrast, MUT3 showed major changes. Virion-like particles had a fried-egg, and filaments a screw-like appearance. The S-promoter mutations MUT1 and MUT2 correlated with viral retention. MUT3 leads to malformed viral particles. Therefore, different regions in the pre-S domain are essential to determine the intracellular localization and extracellular appearance of HBV, and might contribute to the prognosis of chronic HBV infection.
A PRELIMINARY EVALUATION OF ACEPROMAZINE (PLEGICIL)
Authors: JOHN T. FERGUSON
Journal: American Journal of Psychiatry (1958)

Seventy-six per cent of 50 patients who had been resistant to all other therapies responded favorably to a program based on acepromazine's psychosedative action. We feel that these results were obtained because the regimen emphasized individualization of dosage, use of adjunct medications as indicated, and rehabilitation services to guide the patients through the "door to reality" opened by this new psychopharmacological agent.
MIGRAINE WITH ABDOMINAL EQUIVALENT
Authors: N. LIONEL BLITZSTEN
Journal: JAMA (1926)

In a previous communication,<sup>1</sup>a series of twenty-two cases of migraine was reported in which the abdominal symptoms dominated the clinical picture. Great care was used to exclude organic disease of the nervous and other systems by physical examination and other tests and by prolonged observation in many instances for a number of years. It was also pointed out that, with the exception of the few cases reported by Moebius,<sup>2</sup>Schmidt,<sup>3</sup>Ortner,<sup>4</sup>Kuttner,<sup>5</sup>Bary,<sup>6</sup>Mendel,<sup>7</sup>Curschmann,<sup>8</sup>and Bordoni,<sup>9</sup>comparatively little mention is made in the literature of migraine cases in which the abdominal symptoms replaced the hemicrania or greatly overshadowed the headache. The exhaustive monographs of Liveing<sup>10</sup>and Flatau<sup>11</sup>give only scant mention to the form of migraine under discussion. A study of the literature since the date of our previous publication reveals only two additional reports on migraine
The production of inflammatory compounds by Propionibacterium acnes and other skin organisms
Authors: R. P. ALLAKER, J. GREENMAN, R. H. OSBORNE
Journal: British Journal of Dermatology (1987)

Culture supernatants from four species of skin microorganisms (P. acnes, P. avidum, P. granulosum and S. epidermidis) were assayed for smooth muscle contracting substances which are indicative of inflammatory activity. At least three types of smooth muscle contracting substances were detected. These were: first, a substance active on a rat fundic strip preparation and antagonized by N, N-DMT. Activity was enhanced when cultures were grown in the presence of tryptophan. This substance was probably tryptamine. Second, a substance active on a guinea-pig ileum preparation and antagonized by mepyramine. Activity was enhanced when cultures were grown in the presence of histidine. This substance was probably histamine. Third, a substance active on a rat fundic strip preparation but not antagonized by N, N-DMT, epyramine, atropine or indomethacin. Activity was enhanced when cultures were grown in the presence of glucose. This activity was probably due to acetate, propionate or other short-chain fatty-acid salts. Chromatographic analysis confirmed the presence of histamine, tryptamine and short-chain fatty acids in the culture supernatants. These substances if produced in vivo may cause or contribute to inflammation and pain directly without the prior mediation of the immune system. Cell extracts of Propionibacterium species were analysed by bioassay for the presence of prostaglandin-like compounds. These could not be detected in any of the eight strains of organisms tested.
Lung Infection—A Public Health Priority
Authors: Joseph P Mizgerd
Journal: PLoS Medicine (2006)

Emerging lung infections capture the world's imagination because of the potential for pandemics.Recent examples include avian infl uenza and the severe acute respiratory syndrome (SARS).However, even in the absence of new pathogens or pandemics, lung infections have tremendous impact.Lung infections cause more disease than better-recognized threats to the public's health such as cancer, heart attacks, strokes, HIV/AIDS, tuberculosis, or malaria.This persistent and pervasive burden of lung infections receives proportionately little attention from the biomedical and public health communities.
Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial
Authors: Ronald F van Vollenhoven, Pierre Geborek, Kristina Forslind, Kristina Albertsson, Sofia Ernestam, Ingemar F Petersson, Katerina Chatzidionysiou, Johan Bratt
Journal: The Lancet (2012)
THE TREATMENT OF ACUTE PUERPERAL INVERSION
Authors: N. Hypher
Journal: BMJ (1930)

TREATMENT OF ACUTE PUERPERA&L INVERSION.[McAo 179was no evidence of suclh imiprovement.Of tlhe 35 patients taking cod-liver oil, 25 were clinically improved, and 10 were not.The skiagrams of 18 of t4ese 35 indicated pro- gress towards cure, while those of 17 did not.Cases receiving Cases receiving much moderate amlounts Vitamin A and D.Vitamin A and D (Cod-liver Oil).Number.Percentage.
PTEN Loss Confers BRAF Inhibitor Resistance to Melanoma Cells through the Suppression of BIM Expression
Authors: Kim H.T. Paraiso, Yun Xiang, Vito W. Rebecca, Ethan V. Abel, Y. Ann Chen, A. Cecilia Munko, Elizabeth Wood, Inna V. Fedorenko, Vernon K. Sondak, Alexander R.A. Anderson, Antoni Ribas, Maurizia Dalla Palma, Katherine L. Nathanson, John M. Koomen, Jane L. Messina, Keiran S.M. Smalley
Journal: Cancer Research (2011)

This study addresses the role of PTEN loss in intrinsic resistance to the BRAF inhibitor PLX4720. Immunohistochemical staining of a tissue array covering all stages of melanocytic neoplasia (n = 192) revealed PTEN expression to be lost in >10% of all melanoma cases. Although PTEN expression status did not predict for sensitivity to the growth inhibitory effects of PLX4720, it was predictive for apoptosis, with only limited cell death observed in melanomas lacking PTEN expression (PTEN-). Mechanistically, PLX4720 was found to stimulate AKT signaling in the PTEN- but not the PTEN+ cell lines. Liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM) was performed to identify differences in apoptosis signaling between the two cell line groups. PLX4720 treatment significantly increased BIM expression in the PTEN+ (>14-fold) compared with the PTEN- cell lines (four-fold). A role for PTEN in the regulation of PLX4720-mediated BIM expression was confirmed by siRNA knockdown of PTEN and through reintroduction of PTEN into cells that were PTEN-. Further studies showed that siRNA knockdown of BIM significantly blunted the apoptotic response in PTEN+ melanoma cells. Dual treatment of PTEN- cells with PLX4720 and a PI3K inhibitor enhanced BIM expression at both the mRNA and protein level and increased the level of apoptosis through a mechanism involving AKT3 and the activation of FOXO3a. In conclusion, we have shown for the first time that loss of PTEN contributes to intrinsic BRAF inhibitor resistance via the suppression of BIM-mediated apoptosis.
Abstract C29: Prostate cancer detection and localization with diffusion-weighted imaging and 1H-MR spectroscopy
Authors: Akash Singh
Journal: Cancer Research (2012)

Abstract Diffusion-weighted imaging (DWI) of the human with 1.5T MRI gives the insight of Prostate Cancer Tissue details. DWI is now used also for other Liver, Kidney, and Heart Imaging than the brain, and especially focused on detection of Cancer Tissues in prostate.1H-MR spectroscopy technique is used to detect and localize prostate cancer. One difficult sight of 1.5T prostate spectroscopy is the use of a special endorectal coil, it is a thin wire covered with a latex balloon and inserted inside the tail end of the large bowel which is rectum. We detected and identified the prostate cancer by DWI and 3D 1H-MRS with a external phase arrayed multi-coils, this is optimal tumor invasion through bowel wall and adjacent organs. Note: This abstract was not presented at the conference because the presenter was unable to attend. Citation Format: Akash Singh. Prostate cancer detection and localization with diffusion-weighted imaging and 1H-MR spectroscopy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C29.