tbuckley/cabot-search huggingface dataset:
Abstract 161: The role of mTOR in the cisplatin resistant phenotype in ovarian cancer lineage
Authors: Taciane Ladislau, Débora Silva, Klesia Pirola Madeira, Renata Dalmaschio Daltoé, Marcela Ferreira Paes, Alice Laschuck Herlinger, Paulo Cilas Morais Lyra Junior, Ian Victor Silva, Leticia Batista Azevedo Rangel
Journal: Cancer Research (2012)

Abstract Background Ovarian cancer (OVCA) is the second cause of gynecological-cancer deaths in Brazil, being frequently associated to chemotherapy resistance, a characteristic usually associated to PI3K/Akt/mTOR. We herein present data concerning the role of mTORC2 in cisplatin-resistant phenotype acquisition by OVCA cells. Methods Antineoplastic efficacy of cisplatin, doxorubicin, paclitaxel, and rapamycin was accessed, in different combinations, in the OVCA lineage OVCAR3 (cisplatin-resistant, advanced serous OVCA), through cellular metabolic viability (CMV) (MTT method). Cells were cultured in RPMI media supplemented with 10% (v/v) FBS and antibiotics until subconfluence. To characterize the role of mTORC1 or mTORC2 in OVCAR3 MCV, 1.5x105 cells/well were treated according to: EA1) Inhibition of mTORC1: Drugs at IC50 for 24h; EA2) Inhibition of mTORC1 and mTORC2: Rapamycin 100nM for 72h, followed by drugs at IC50 for 24h. Modulation of MTOR expression by PKA, PKC, and PI3K was investigated by real time RT-PCR. Statistical analysis was performed using PrismaGraphPad version 5.1. Findings OVCAR3 CMV was not significantly changed by cisplatin (IC50 0,08mM) nor paclitaxel (IC50 0,06nM) or rapamycin (IC50 0,02nM) (CMV 95%, 100%, 100%, respectively), but by doxorubicin (IC50 0,02nM) (CMV 60%), especially in combination with cisplatin (CMV 31%), following EA1. Considering the irreversible doxorubicin-induced cardiotoxicity, we pursued with EA2. Intriguingly, OVCAR3 cisplatin sensitivity was, at least partially, recovered (CMV 65%). No addictive effect was observed with cisplatin/doxorubicin following EA2 (CMV 60%), suggesting that OVCA-resistant patient might benefit from less toxic rapamycin-based chemotherapy, leaving doxorubicin for palliative final-staged disease management. Finally, neither PKA nor PI3K modulate MTOR expression; however, PKC suppresses its transcription by 4.42-fold. Interpretation Altogether, our data suggest that mTORC2, but not mTORC1, might influence cisplatin sensitivity in OVCA. Moreover, PKC inhibits the expression of MTORC in cisplatin-resistant OVCA. We propose that the inhibition of mTORC2 followed by cisplatin treatment might lead to a conjunction of autophagic cell death and apoptosis in OVCA. Of remarkable clinical interest, we point to the urge of better design clinical trials, in which not only novel drugs are tested, but also the chronological order of drugs administration to the patient is seen as crucial for treatment efficacy. 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 161. doi:1538-7445.AM2012-161
PROGNOSTIC SIGNIFICANCE OF QUANTITATIVE MEASURES OF MYOCARDIAL INFARCT PATHOLOGY IN SURVIVORS OF ST-ELEVATION MYOCARDIAL INFARCTION
Authors: David Carrick, Caroline Haig, Sam Rauhalammi, Nadeem Ahmed, Ify Mordi, Margaret McEntegart, Mark Petrie, Hany Eteiba, Stuart Hood, Stuart Watkins, Mitchell Lindsay, Ahmed Mahrous, Aleksandra Radjenovic, Ian Ford, Niko Tzemos, Keith Oldroyd, Colin Berry
Journal: Journal of the American College of Cardiology (2015)
Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels.
Authors: H M Loree, R D Kamm, R G Stringfellow, R T Lee
Journal: Circulation Research (1992)

It is likely that factors other than stenosis severity predispose some atherosclerotic plaques to rupture. Because focal increases in circumferential stress may be an important mechanism of plaque rupture, we examined peak circumferential stress of atherosclerotic lesions by using finite element analysis based on idealized two-dimensional cross sections of diseased vessels similar to intravascular ultrasound images. The study was designed to test the hypothesis that subintimal plaque structural features such as thickness of the fibrous cap are more important factors in the distribution of stress in the plaque than stenosis severity. The analysis incorporated equilibrium biomechanical parameters from normal and diseased vessels and determined the stress distribution within the plaque at a mean luminal internal pressure of 110 mm Hg. With a constant luminal area reduction of 70%, maximum circumferential stress (sigma max) normalized to luminal pressure (sigma max/P) increased from 6.0 to 24.8 as the thickness of the lipid pool was increased from 38% to 54% of the plaque thickness because of the thinner fibrous cap over the lipid pool. When the lipid pool thickness was constant, increasing the stenosis severity from 70% to 91% by increasing the fibrous cap thickness decreased sigma max/P from 24.8 to 4.7. When no lipid pool was present and the stenosis severity was increased from 70% to 99%, sigma max/P decreased from 5.3 to 4.7. Thus, reducing the fibrous cap thickness dramatically increases peak circumferential stress in the plaque, whereas increasing the stenosis severity actually decreases peak stress in the plaque.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma somatostatin 28 increases in response to feeding in man.
Authors: K S Polonsky, S E Shoelson, H M Docherty
Journal: Journal of Clinical Investigation (1983)

Tissue somatostatin-like immunoreactivity (SLI) consists of a number of molecular species including the cyclic tetradecapeptide or SRIF, an N-terminally extended form of SRIF termed somatostatin-28, as well as larger precursor peptides. The function and nature of circulating SLI is not well understood. In this report, we describe techniques for the definition of the components of plasma SLI in normal human plasma. Plasma SLI measured after gel filtration on Bio-gel P-6 columns was found to consist of from 1-3 peaks. The void volume peak was present in greatest concentration (34.2 +/- 8.9 pg/ml) and did not increase in response to a mixed meal. Very low levels of two additional peaks of SLI activity were found. To further characterize these peaks, 10-ml plasma samples were extracted and concentrated on octadecylsilyl silica (C-18) cartridges with subsequent fractionation on Bio-gel P-6 columns. The two peaks that coeluted with synthetic SRIF and S-28 markers, respectively, were present in concentrations of 5.4 +/- 1.4 and 4.8 +/- 1.9 pg/ml in fasting plasma. In response to a mixed meal, the SLI14 peak doubled (12.9 +/- 2.4 pg/ml) while the SLI28 peak increased to 29.9 +/- 7.2 pg/ml at 120 min. These results provide evidence that S-28 circulates in human plasma and its increase after feeding is consistent with a possible biological role for this peptide.
Transient and Permanent Deafness Following Treatment with Ethacrynic Acid in Renal Failure.
Authors: V. K. G. Pillay
Journal: Annals of Internal Medicine (1969)

s1 May 1969Transient and Permanent Deafness Following Treatment with Ethacrynic Acid in Renal Failure.V. K. G. Pillay, M.D., F. D. Schwartz, M.D., K. Aimi, M.D., R. M. Kark, M.D., F.A.C.P.V. K. G. Pillay, M.D.Search for more papers by this author, F. D. Schwartz, M.D.Search for more papers by this author, K. Aimi, M.D.Search for more papers by this author, R. M. Kark, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1095_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAmong the numerous adverse effects of ethacrynic acid, the development of acute transient deafness has received some attention. We have encountered this complication in five uremic patients treated with ethacrynic acid, in three of whom the deafness was permanent. Deafness occurred whether the treatment was oral or intravenous. None of the patients had any hearing loss before treatment with ethacrynic acid. In each instance there was a clear correlation between the onset of deafness and the use of ethacrynic acid. In two patients withdrawal of the drugs resulted in immediate improvement in hearing; partial in one; and complete in another.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1095-1095KeywordsDeafnessDrugsHearingRenal failure Issue Published: 1 May 1969 PDF downloadLoading ...
APPARATUS FOR FREEZING AND DRYING VIRUS IN LARGE QUANTITIES UNDER UNIFORM CONDITIONS
Authors: Johannes H. Bauer, Edward G. Pickels
Journal: The Journal of Experimental Medicine (1940)

1. The apparatus described was designed for the desiccation under uniform conditions of large quantities of yellow fever virus in the frozen state. 2. Several hundred cubic centimeters of virus material, distributed in small containers, have been desiccated simultaneously to almost complete dryness and with no appreciable loss of infectivity. 3. Good keeping qualities of the virus activity are insured by sealing the containers either while evacuated or after filling with dry nitrogen.
Potentiating and depressive effects of ouabain and potassium-free solutions on rat mesenteric resistance vessels.
Authors: M J Mulvany, H Nilsson, J A Flatman, N Korsgaard
Journal: Circulation Research (1982)

We have investigated the in vitro effects of ouabain and K-free solutions on some pharmacological and electrophysiological properties of rat mesenteric resistance vessels (internal diameter approximately 190 micrometers). Vessels were mounted as ring preparations on a myograph capable of measuring their isometric wall tension. In normal saline solutions, vessels did not exhibit any tone and had a membrane potential of -54 mV. Both 1 mM ouabain and K-free solutions caused a transient depolarization of 5-8 mV; thereafter the membrane slowly depolarized to about -45 mV after 30 minutes. There was no mechanical response to ouabain, but K-free solutions caused a transient development of tension which could be inhibited by phentolamine (1 microM). In norepinephrine-activated vessels, exposure to ouabain or K-free solutions caused a small depolarization and an increase in tension. Long-term (30-minute) exposure to 1 mM ouabain or K-free solutions reduced the amplitude of norepinephrine responses and, for the lower (but not the higher) norepinephrine concentrations, the membranes were about 14 mV more depolarized than control. The mechanical responses to a cocktail of norepinephrine in a high potassium solution were, however, unaffected. Re-exposure to normal saline solution produced a transient hyperpolarization and transiently eliminated the norepinephrine response, but thereafter the membrane potential and response returned to normal. The results indicate that ouabain and K-free solutions can have both short-term potentiating and long-term depressive effects on the mechanical response of rat mesenteric resistance vessels to norepinephrine.
Screening Colonoscopy vs Flexible Sigmoidoscopy—Reply
Authors: Alfred I. Neugut, Benjamin Lebwohl
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Is gastrin a major determinant of basal lower esophageal sphincter pressure? A double-blind controlled study using high titer gastrin antiserum.
Authors: R K Goyal, J E McGuigan
Journal: Journal of Clinical Investigation (1976)

Studies were performed in anesthetized opossums to determine the influence of binding of circulating gastrin with a high titer gastrin antiserum on lower esophageal sphincter pressure. Gastrin antiserum or control antiserum was administered intravenously in successive doses of 0.02, 0.1, and 0.5 ml/kg on separate days. The lower esophageal sphincter pressures were measured for 1 h before and for 1 h after antiserum administration. The control serum caused no binding of opossum circulating gastrin, nor did it modify lower esophageal sphincter pressure. On the other hand, the administration of gastrin antiserum resulted in the binding of 85-90% of circulating gastrin, but it did not reduce sphincter pressure. A continuous infusion of 0.25 mug-kg-1-h-1 of synthetic human gastrin I caused a significant (P less than 0.05) increase in the sphincter pressure, a 30-fold increase in gastric acid output, and a fourfold increase in immunoreactive gastrin in the opossum blood. Prior treatment with 0.1 ml/kg of gastrin antiserum antagonized and 0.2 ml/kg of the antiserum abolished the gastrin-stimulated gastric acid secretion and the stimulating effect of gastrin on lower esophageal sphincter pressure. However, neither dose of antiserum modified basal lower esophageal sphincter pressure. It is concluded that circulating gastrin may be an important determinant of basal sphincter pressure.
The effect of inhaled leukotriene B4 in normal and in asthmatic subjects.
Authors: S E Sampson, J F Costello, A P Sampson
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Leukotriene (LT) B4 is a potent leukocyte chemotaxin that increases bronchial responsiveness in animal models. In a double-blind, placebo-controlled crossover study we examined the effects of LTB4 on lung function, bronchial responsiveness, and blood leukocyte counts in six normal subjects and in six subjects with mild asthma who inhaled mean +/- SEM doses of 17.6 +/- 3.4 and 18.2 +/- 1.9 microg LTB4, respectively, or placebo. There were no significant changes in specific airway conductance or bronchial responsiveness in either normal subjects or asthmatics for as long as 24 h after inhalation. In the normal subjects, LTB4 rapidly reduced blood neutrophil counts to 19.8 +/- 6.3% of baseline at 5 min (p = 0.0003 compared with placebo), followed by a neutrophilia of 307 +/- 40% of baseline at 30 min (p = 0.007). Similar changes occurred in asthmatics, with a neutropenia at 5 min (69.6 +/- 5.8%; p = 0.003) and a neutrophilia at 30 min (183 +/- 17.2%; p = 0.037). The neutrophilia was not sustained in either subject group, with values being no different from that of placebo by 6 h. The asthmatics had significantly less neutropenia (p = 0.005) and less neutrophilia (p = 0.018) than did the normal subjects. Placebo inhalation had no effect on any parameter in either group. The smaller neutrophil responses in asthmatics may reflect desensitization of blood neutrophils in vivo because of chronic exposure to endogenous LTB4.
Chronic urticaria and macroglobulinemia (Schnitzler's syndrome): Report of two cases
Authors: Michel Janier, Douceline Bonvalet, Marie-France Blanc, Françoise Lemarchand, Bénédicte Cavelier, Alain Ribrioux, Béatrice Aguenier, Jean Civatte
Journal: Journal of the American Academy of Dermatology (1989)
Rat glomerular mesangial cells synthesize basic fibroblast growth factor. Release, upregulated synthesis, and mitogenicity in mesangial proliferative glomerulonephritis.
Authors: J Floege, E Eng, V Lindner, C E Alpers, B A Young, M A Reidy, R J Johnson
Journal: Journal of Clinical Investigation (1992)

Mesangial injury and cell proliferation are frequent findings in various glomerular diseases in man. Previous studies have demonstrated that basic fibroblast growth factor (bFGF) is a potent mesangial cell mitogen in vitro. To further elucidate the role of bFGF in rat mesangial cell (RMC) proliferation, we examined whether RMC synthesize bFGF in vitro and whether bFGF is involved in mesangial proliferation in vivo. Cultured RMC expressed bFGF protein (23, 21.5, and 18 kD forms) and bFGF mRNA, and released biologically active bFGF into the culture medium after antibody- and complement-mediated injury. Normal rat glomeruli in vivo contained no detectable bFGF mRNA, but bFGF protein (23 and 21.5 kD) could be demonstrated, which immunolocalized to the mesangium. Glomerular bFGF decreased markedly during the acute phase of glomerulonephritis induced by anti-Thy 1.1 antibody, compatible with mesangial bFGF release after complement-mediated mesangiolysis. During the subsequent mesangial proliferative phase, glomerular bFGF protein and mRNA increased above normal. Intrarenal infusion of heparin did not affect the bFGF immunostaining of glomeruli at this stage, indicating a predominantly intracellular localization of the bFGF. The capability of bFGF to mediate proliferation in the anti-Thy 1.1 model was further supported by experiments in which intravenous bFGF given 24 h after a subnephritogenic dose of anti-Thy 1.1 antibody led to a 4.9- to 5.1-fold increase in glomerular cell proliferation (with > 60% of the cells identified as mesangial cells by double immunolabeling). No such increase was observed in normal rats injected with bFGF. These data show that mesangial cells produce and release bFGF after injury and that bFGF is mitogenic for injured mesangial cells in vivo. Release of mesangial cell bFGF thus may be an important mechanism involved in the initiation of mesangial cell proliferation in vivo.
FOODS THAT COMMONLY DISAGREE WITH PEOPLE
Authors: WALTER C. ALVAREZ
Journal: JAMA (1935)

Which are the foods difficult of digestion or likely to cause distress of one kind or another? Which are the most likely to cause gas, abdominal discomfort, heartburn, regurgitation, "biliousness" or urticaria? Surely, after thousands of years of cumulative experience, we physicians should be well prepared to answer these questions which are being put to us several times a day; and yet, it does not look as if we were. Today the average physician, when asked for advice as to diet, is likely to warn against the eating of fried or greasy or rich foods, or of foods that he himself cannot digest; or he will give a printed list, which may fit the needs of his patient about as well as the key to one door fits the lock of another. And if the patient should protest that he is unable to partake of, let us say, milk or
Treatment of Genetic Hormonal Deficiencies by Nicotine
Authors: Richard J. Hickey
Journal: JAMA (1985)

<h3>To the Editor.—</h3> It is not clear in the letters by Berman and Hogue<sup>1</sup>and by Sexton and Hebel<sup>2</sup>concerning the relationship between maternal cigarette smoking and infant birth weight that the authors understand that biologic causality<i>cannot</i>be established by statistical evidence alone.<sup>3,4</sup>Correctly used, statistical methods can<i>reject</i>hypotheses, but they can<i>never</i>validate them.<sup>3</sup>We noted a positive association between maternal prepregnant weight and mean birth weight and also between maternal height and mean birth weight.<sup>4</sup>Furthermore, it was suggested<sup>4</sup>that the arbitrary 2,500-g birth weight "break-point" criterion between presumably healthy and unhealthy infants is surely an oversimplification. If both parents are, say, 160 cm (5 ft 3 in) tall or less and weigh 58.8 kg (130 lb) or less, as compared with parents 178 cm (5 ft 10 in) tall or taller and weighing 72.3 kg (160 lb) or more,
Impaired tracheobronchial clearance in patients with mild stable asthma.
Authors: J R Bateman, D Pavia, N F Sheahan, J E Agnew, S W Clarke
Journal: Thorax (1983)

Tracheobronchial mucociliary clearance was measured with the radioaerosol technique in 25 patients with stable, mild asthma, none of whom was taking systemic corticosteroids. The results were compared with those obtained from a control group of 25 healthy subjects matched for age and sex. All patients and healthy subjects were non-smokers. Ventilatory function was significantly impaired in the asthmatic group, which resulted in a more central initial tracheobronchial deposition of inhaled radioaerosol than in the control group. Despite the shorter transit path along the ciliated airways for the tracer radioaerosol in the asthmatic group, mucociliary clearance was found to be significantly poorer than in the healthy control group. This may be important with respect to bronchial mucus plugging.
Congestive Heart Failure Masquerading as Primary Pulmonary Disease.
Authors: E. C. Rosenow
Journal: Annals of Internal Medicine (1969)

s1 May 1969Congestive Heart Failure Masquerading as Primary Pulmonary Disease.E. C. Rosenow III, M.D., C. E. Harrison, M.D., F.A.C.P.E. C. Rosenow III, M.D.Search for more papers by this author, C. E. Harrison, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1081_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCongestive heart failure, particularly when it is chronic and insidious, may not exhibit the typical signs of progressive dyspnea, cough, orthopnea, paroxysmal nocturnal dyspnea, or edema with weight gain. In addition, the roentgenographic findings may be atypical. Thus, the combination of misleading clinical and roentgenographic findings and the absence of positive physical findings such as rales and cardiac gallop may lead the clinician away from the correct diagnosis of congestive heart failure.A series of cases of congestive heart failure is presented in which the original diagnosis was primary pulmonary disease. The pulmonary diagnoses included diffuse pulmonary fibrosis, asthmatic, bronchitis,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, Minnesota PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1081-1081KeywordsBronchitisDyspneaEdemaHeart failurePulmonary diseasesPulmonary fibrosisWeight gain Issue Published: 1 May 1969 PDF downloadLoading ...
Intérèt du vinaigre pour le diagnostic de la métaplasie intestinale et de la dysplasie de haut grade (DHG) sur endobrachyoesophage; comparaison avec la chromoendoscopie électronique (NBI)
Authors: J Boyer, A Croué
Journal: Endoscopy (2008)

Introduction: L'endobrachyoesophage (EBO) est défini par la présence au dessus de la jonction oeso-gastrique d'une muqueuse glandulaire en métaplasie intestinale parielle ou diffuse; le diagnostic est endoscopique et histologique; les progrès de l'endoscopie électronique permettent actuellement une analyse en haute définition et un großissement des images dont les performances sont accrues soit par l'instillation de colorants ou/et par des artifices électroniques type NBI; parmi les substances utilisées l'acide acétique à 1,5% ou plus simplement le vinaigre est le plus utilisé; le but de cette présentation video est de montrer les différents aspects de la métaplasie intestinale et de la DHG obtenus avec le vinaigre en les comparant à la chromoendoscopie électronique (NBI).