tbuckley/cabot-search huggingface dataset:
Abstract 4957: Role of tumor-derived exosomes in growth and metastasis of breast cancer
Authors: Radha Munagala, Ramesh Gupta
Journal: Cancer Research (2014)

Abstract Breast cancer (BC) mortality rates have decreased over last 30 years, largely due to early detection and improved treatment modalities, particularly targeted therapies. However, metastasis relentlessly drives mortality. The pervasive mortality from metastasis highlights the shortcomings of traditionally accepted hypotheses on the metastatic process. The mechanisms by which malignant tumors leave the primary tumor site, invade lymphatics, and metastasize to regional lymph nodes are complex and interrelated. Exosomes are biological nanovesicles (∼30-100 nm) of endocytic origin. Exosomes mediate local and horizontal transfer of information, such as mRNAs, miRNAs and proteins. They are indicated to play a significant role in the genesis of tumor, growth and metastasis. Recent advances in the exosome biology suggest that tumor-derived exosomes (TDEs) are critical mediators of tumorigenesis and can incite a pro-angiogenic signaling program capable of remodeling tissue matrices. However, the role of TDEs in BC metastasis remains elusive. In this study, we examined the role of exosomes in breast cancer metastasis using cell culture studies. We made the following observations: i) exosomes derived from BC cells had a mean size of 92 nm and carried exosomal marker proteins CD63 and CD81, ii) uptake of exosomes from highly metastatic BC cells (MDA-MB-231) by non-metastatic recipient cells (BT474 and T47D), iii) faster wound healing rate, increased migratory behavior, and invasiveness in recipient cells treated with metastatic BC exosomes, iv) increased endothelial cell tube formation, reflective of angiogenesis ability with exosomes from metastatic BC cells, v) modulation in expression levels of key EMT-associated proteins in non-metastatic cells treated with metastatic BC exosomes favoring EMT shift, vi) difference in metastasis-associated miRNAs levels in exosomes from invasive and non-invasive BC cells. Our data that suggest exosomes from metastatic BC cells carry the cargo essential for EMT and have the ability to change phenotypic traits of the recipient cells. Determining the role of exosomes in BC metastasis and characterization of BC exosomes components (proteins, mRNA and miRNA) will have great potential to uncover new targets and lead to new therapies for metastatic disease. Citation Format: Radha Munagala, Ramesh Gupta. Role of tumor-derived exosomes in growth and metastasis of breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4957. doi:10.1158/1538-7445.AM2014-4957
Natural killer T cells exacerbate liver injury in a transforming growth factor β receptor II dominant-negative mouse model of primary biliary cirrhosis
Authors: Ya-Hui Chuang, Zhe-Xiong Lian, Guo-Xiang Yang, Shang-An Shu, Yuki Moritoki, William M. Ridgway, Aftab A. Ansari, Mitchell Kronenberg, Richard A. Flavell, Bin Gao, Eric M. Gershwin
Journal: Hepatology (2007)

Primary biliary cirrhosis (PBC) is an organ-specific autoimmune liver disease characterized by the presence of antimitochondrial antibodies and the destruction of small intrahepatic bile ducts with portal inflammation. In previous studies, we reported that both CD1d expression and the frequency of CD1d-restricted natural killer T (NKT) cells were increased in the livers of patients with PBC. To define a specific role of CD1d-restricted NKT cells in the pathogenesis of PBC, particularly early events, we investigated the function of hepatic CD1d-restricted NKT cells in our transforming growth factor β (TGF-β) receptor II dominant-negative (dnTGFβRII) mouse model of PBC. We generated CD1d−/− and CD1d+/− dnTGFβRII mice and performed a comparative study of liver immunopathology. We report herein that these dnTGFβRII mice demonstrate a massive increase of hyperactive CD1d-restricted NKT cells within the hepatic tissues. CD1d−/−dnTGFβRII mice, which lack CD1d-restricted CD1d-restricted NKT cells, exhibit significantly decreased hepatic lymphoid cell infiltrates and milder cholangitis compared with CD1d+/−dnTGFβRII mice. Interestingly, there was a significant increase in the production of interferon-γ in hepatic CD1d-restricted NKT cells activated by α-galactosylceramide in young but not older dnTGFβRII mice, suggesting an age-dependent role of CD1d-restricted NKT cells. Conclusion: These data demonstrate that CD1d-restricted NKT cells in dnTGFβRII mice are a critical factor in liver injury. (Hepatology 2008.)
The Diagnosis of Pulmonary Embolism
Authors: Mitchell Phillip Laks
Journal: JAMA (1990)

<h3>To the Editor. —</h3> In Dr Bone's<sup>1</sup>editorial accompanying the publication of the PIOPED study in<i>JAMA</i>,<sup>2</sup>the algorithm for the workup of a patient with a clinically suspected pulmonary embolism and hypoxemia mandates a pulmonary angiogram in patients with a high-probability ventilation/perfusion scan if a noninvasive study (impedance plethysmography or duplex ultrasound) yields normal results. Although it is intriguing to speculate on how results from these other noninvasive tests should modify our triage of patients, there is no evidence suggesting that all these patients require an angiogram. The PIOPED study has shown that a high-probability scan has a sensitivity and specificity of 41% and 97%, respectively, which for a population with a prevalence of pulmonary embolism of 33% (about average for the literature) corresponds to a positive predictive value of 88% for pulmonary embolism (or 91% for patients with no history of prior pulmonary embolism). Certainly, an
Family Planning Advertisement
Authors: J. L. McCallum
Journal: BMJ (1959)

Little is known about cardiac uptake kinetics of idarubicin, including a possible protective role of P-glycoprotein (Pgp)-mediated transport. This study therefore investigated uptake and negative inotropic action of idarubicin in the single-pass isolated perfused rat heart by using a pharmacokinetic/pharmacodynamic modeling approach. Idarubicin was administered as a 10-min constant infusion of 0.5 mg followed by a 70-min washout period in the absence and presence of the Pgp antagonists verapamil or amiodarone. Outflow concentration and left ventricular developed pressure were measured and the model parameters were estimated by simultaneous nonlinear regression. The results indicate the existence of a saturable, Michaelis-Menten type uptake process into the heart (<i>K</i><sub>m</sub> = 3.06 μM,<i>V</i><sub>max</sub> = 46.0 μM/min). Verapamil and amiodarone significantly enhanced the influx rate (<i>V</i><sub>max</sub> increased 1.8-fold), suggesting that idarubicin is transported by Pgp directly out of the membrane before it gets into the cell. Verapamil and amiodarone attenuated the negative inotropic action of idarubicin, which was linked to the intracellular concentration of idarubicin.
Effect of vagotomy on the gastric secretion of acid chloride and pepsin in response to an antral stimulus and to insulin and maximal histamine stimulation.
Authors: F I Tovey, M Swaminathan, K Parker, A Daniell
Journal: Gut (1968)

INSULIN PHASE Soluble insulin was given intravenously (15 units for patients weighing 100 to 120 lb; 10 units for patients under 100 lb), and the stomach was emptied after 10 minutes, the aspirate being discarded.Three runs of 100 ml of N saline with phenol red were injected through the tube and aspirated after 10 minutes.659
Autoantibodies and Pregnancy Loss
Authors: Susan Cowchock
Journal: New England Journal of Medicine (1997)

Two articles in this issue of the Journal 1,2 focus on autoantibodies as a cause of pregnancy loss. Rand and coworkers describe a mechanism by which antiphospholipid antibodies could cause placental thrombosis and infarction. They found that antiphospholipid antibodies lower levels of annexin V, a surface anticoagulant present in cultured vascular and trophoblast cells that has a high affinity for anionic phospholipids; by this mechanism, the time to fibrin formation is reduced when plasma is incubated with cells previously incubated with antiphospholipid antibody.1 Laskin and coworkers report the results of a randomized trial of the efficacy of prednisone treatment with . . .
Common Genetic Variation in <i>KCNH2</i> Is Associated With QT Interval Duration
Authors: Christopher Newton-Cheh, Chao-Yu Guo, Martin G. Larson, Stacy L. Musone, Aarti Surti, Amy L. Camargo, Jared A. Drake, Emelia J. Benjamin, Daniel Levy, Ralph B. D’Agostino, Joel N. Hirschhorn, Christopher J. O’Donnell
Journal: Circulation (2007)

Background— QT prolongation is associated with increased risk of sudden cardiac death in the general population and in people exposed to QT-prolonging drugs. Mutations in the KCNH2 gene encoding the HERG potassium channel cause 30% of long-QT syndrome, and binding to this channel leads to drug-induced QT prolongation. We tested common KCNH2 variants for association with continuous QT interval duration. Methods and Results— We selected 17 single nucleotide polymorphisms and rs1805123, a previously associated missense single nucleotide polymorphism, for genotyping in 1730 unrelated men and women from the Framingham Heart Study. rs3807375 genotypes were associated with continuous QT interval duration in men and women (2- df P =0.002), with a dominant model suggested ( P =0.0004). An independent sample of 871 Framingham Heart Study men and women replicated the association (1-sided dominant P =0.02). On combined analysis of 2123 subjects, individuals with AA or AG genotypes had a 0.14-SD (SE, 0.04) or 3.9-ms higher age-, sex- and RR-adjusted QT interval compared with GG individuals ( P =0.00006). The previously reported association of rs1805123 (K897T) replicated under a dominant (AA/AC, 0.12 SD [SE, 0.07] or 3.1 ms higher versus CC; 1-sided P =0.04) or additive model (0.06 SD [SE, 0.03] or 1.6 ms higher per A allele; 1-sided P =0.01). Conclusions— Two common genetic variants at the KCNH2 locus are associated with continuous QT interval duration in an unselected community-based sample. Studies to determine the influence of these variants on risk of sudden cardiac death and drug-induced arrhythmias should be considered.
Abstract 1992: Ganoderma lucidum (Reishi) induces autophagy in inflammatory breast cancer by regulation of the mTOR signaling pathway
Authors: Raysa Rosario-Acevedo, Ivette Suárez-Arroyo, Alexandra Aguilar-Pérez, Luis A. Cubano, Michelle M. Martínez-Montemayor
Journal: Cancer Research (2012)

Abstract The control of cell growth by the mammalian target of rapamycin (mTOR) signaling pathway and autophagy are relevant to disease, as altered regulation of either pathway may result in tumorigenesis. Autophagy is a regulated pathway involving the lysosomal degradation of cytoplasmic components and organelles. Activation of the human autophagy-initiation kinase (ULK1) is directly controlled by mTOR and is a critical part of the autophagy machinery. In this study we test the autophagy inducing effects of the medicinal mushroom Ganoderma lucidum (Reishi) in the patient derived inflammatory breast cancer (IBC) cell line SUM-149 and in the non-cancerous mammary epithelial cell line MCF10A. IBC is a rare, lethal and aggressive form of locally advanced breast cancer that has a poor prognosis and no targeted therapy. Herein, we demonstrate that Reishi modulates the expression of autophagy related molecules depending on treatment time. At 2h post-Reishi treatment SUM-149 cells show that ULK1, Atg5, Atg12, Beclin1 and the microtubule-associated protein 1 light chain 3 (LC3) are α1.2 fold upregulated. Furthermore, autophagosomal structures were identified in SUM-149 but not in MCF10A Reishi treated cells. At 4h post-Reishi Atg5 and Atg12 (required for phagophore formation) are ∼1.5 fold upregulated, while at 6h LC3 expression (involved in autophagosome formation) is ∼2 fold upregulated compared to vehicle. We also show that autophagy induction in SUM-149 cells is mediated via downregulation of the PI3K/mTOR signaling pathway. Reishi downregulates PI3K (p85 and p110), mTOR phosphorylation and reduces the expression of Raptor, which is the regulatory subunit of mTORC1, the complex that directly regulates proteins involved in autophagy. Rictor, the regulatory subunit of the mTORC2 complex, which inhibits autophagy indirectly through Akt is also downregulated by Reishi. We demonstrate that Reishi has great potential to be used as an anti-IBC-therapeutic. This project was sponsored by Title V PPOHA grant number P031M105050 from the US Dept of Education to UCC, and NIH/RCMI 2G12RR003035 to UCC. 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 1992. doi:1538-7445.AM2012-1992
THE RELIEF OF PROSTATIC OBSTRUCTION
Authors: CLYDE W. COLLINGS
Journal: JAMA (1934)

Prostatic obstruction is relieved in one of two ways: through the cysto-urethroscope or through a suprapubic or perineal incision. It is of vital importance to the patient that the bladder neck obstruction be removed —if not, the resultant renal insufficiency will probably remove the patient.  Prostatectomy is too well known to most surgeons for me to comment on any particular feature of the operation. However, it is my present belief that a patient suffering from benign enlargement will be better off with a prostatectomy than with transurethral surgery, in the hands of many urologic surgeons (especially those who perform only the odd transurethral operation).  Prostatic bars, obstructing prostatic carcinoma and scars, slight and moderate intra-urethral lateral and median lobes are ideally suited for urethroscopic excision by the trained transurethral surgeon. The markedly enlarged prostate, bulging into the rectum and urethra, had best be removed by prostatectomy. 1   A report of
Tortuosity of the innominate artery. Failure of retrograde catheterization of left side of heart by brachial arterial route
Authors: G. Bousvaros
Journal: JAMA (1968)

Tortuosity of the innominate artery that does not produce a radiographic shadow was found to be a frequent obstacle to the passage of a catheter from the right brachial artery into the arch of the aorta and to the subsequent manipulation of the catheter into the left ventricle or coronary ostia. Prolonged attempts to negotiate the tortuous vessel resulted in nonfatal dissection and perforation of the innominate artery in two patients.
"Fish-eye Sign" in Scintigraphy of Benign Thyroid Nodule
Authors: MERCEDES VAQUEIRO, HOSSEIN GHARIB, HEINZ W. WAHNER
Journal: Clinical Nuclear Medicine (1985)

An unusual scintigraphic appearance of a benign adenomatous nodule in the thyroid is described which showed a central core of functional tissue surrounded by a rim of nonfunctioning tissue and degenerative changes. The descriptive term “fish-eye sign” is proposed. The characterization of tissue by scintigraphy prior to fine needle aspiration may be helpful in its interpretation.
A Thread as a Nidus of a Common Bile Duct Calculus - Findings during Endoscopic Lithotripsy
Authors: W. Ormann
Journal: Endoscopy (1989)

Suture material can serve as a nidus for common bile duct calculi. We saw an unusually long thread projecting from a mixed common duct stone in a woman 30 years after cholecystectomy. The calculus was removed endoscopically after mechanical lithotripsy. The implications of this observation, in particular as a potential complication, are discussed.
The importance of age and smoking in evaluating adverse cytogenetic effects of exposure to environmental agents.
Authors: J D Tucker, D H Moore
Journal: Environmental Health Perspectives (1996)

Fluorescence in situ hybridization with chromosome-specific composite DNA probes (chromosome painting) is a reliable and efficient method for detecting structural chromosome aberrations. Painting is now being used to quantify chromosome damage in many human populations. In one such study we evaluated 91 unexposed people ranging in age from birth (cord bloods) to 79. We established a baseline frequency of stable aberrations that showed a highly significant curvilinear increase with age (p &lt; 0.00001) that accounted for 70% of the variance among donors. The magnitude of this effect illustrates the importance of understanding the cytogenetic changes that occur with age, which is particularly important for quantifying the effects of prior adverse environmental, occupational, or accidental exposure. In this paper we use the data obtained in our previous study to characterize the distribution of stable aberrations by age and pack-years of cigarette smoking. We also provide estimates of the number of cell equivalents that need to be scored to detect a given increase in aberrations above the background level surveyed in this population.
Prevalence of Antibody to Current Influenza Viruses and Effect of Vaccination on Antibody Response
Authors: M. S. Pereira, P. Chakraverty, G. C. Schild, M. T. Coleman, W. R. Dowdle
Journal: BMJ (1972)

The extent of antibody to the influenza virus A/Hong Kong/68 (H3N2) after four years of prevalence was investigated in Britain and in the U.S.A. The results indicated a high incidence in both populations. The prevalence of antibody to a variant A/England/42/72 (H3N2) which has been causing epidemics of influenza in the southern hemisphere during the middle months of 1972 was also investigated. The differences reflect the shift in antigenic content of this variant, and although the overall proportion of the sera with antibody at > 1/40 was 37%, some age groups had an incidence of only 20% or less with antibody at this level. A commercial inactivated A/Hong Kong/68 influenza vaccine was given to a group of volunteers in Britain to see how effective it might be in stimulating antibody to the variant A/England/42/72. The antibody responses were better than expected from earlier vaccine studies, and 63% of the vaccinees developed antibody to the A/England/42/72 to levels thought likely to be protective. This suggested that until a vaccine made with the variant A/England/42/72 becomes available the present A/Hong Kong/68 vaccine would be of use to protect those at special risk this winter.
A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with Novastan and TPA (MINT) study
Authors: Ik-Kyung Jang, David F.M Brown, Robert P Giugliano, H.Vernon Anderson, Douglas Losordo, Jose C Nicolau, Oscar P Dutra, Oscar Bazzino, Victor Molina Viamonte, Roberto Norbady, Alvaro Sosa Liprandi, Thomas J Massey, Robert Dinsmore, Richard P Schwarz
Journal: Journal of the American College of Cardiology (1999)
Failure to Diagnose Myocardial Infarction
Authors: Dwight K. Oxley
Journal: JAMA (1984)

To the Editor.—  In discussing why clinicians missed 47% of 100 consecutive autopsy-proved acute myocardial infarctions, Zarling and coauthors 1 list four reasons, the first of which is unjustified dependence on misleading laboratory studies. This statement is itself misleading, since it is  conclusion not supported by the authors' biochemical findings.  The authors use biochemical strategies for which there is no support in standard texts of laboratory medicine or scientific articles. Major reliance was placed on individual SGOT, total lactic dehydrogenase (LDH), and total creatine kinase (CK) results. We are expected to accept that their numerical criteria were developed from a previous unpublished study in our institution. Moreover, we are assured that  enzyme levels were considered diagnostic of myocardial infarction only if there was an absence of other enzyme-elevating pathological conditions. We are not told how these critically important absences were established, except that the patients all received autopsies
Effects of triiodothyronine on the anemia of chronic renal failure
Authors: José Ferrer, Rafael García, Lírimo Rubio, Bernardo Rodríguez‐Itube, María Diez‐Ewald
Journal: American Journal of Hematology (1978)

The present study was done in order to determine whether treatment with triiodothyronine (T3) would improve the anemia of chronic renal insufficiency. Four patients with stable renal failure and anemia were treated with 75 microgram/day of T3 for a period of four weeks. The patients were not in chronic dialysis, had normochromic normocytic anemia and hypocellular bone marrow, and showed no evidence of external blood loss during the study. They had received no iron, folic acid, or androgenic steroids for at least six months prior to the study. The administered dose of T3 was adequate to depress the serum levels of thyroid-stimulating hormone (TSH); however, there was no detectable improvement in the levels of hemoglobin, hematocrit, bone marrow cellularity, serum and erythrocyte folate determinations, serum iron (Fe), 59Fe half-life, plasma iron turnover rate, percentage Fe incorporated into red blood cells, or in the ratio of surface radioactive counting over bone marrow/liver and spleen. It is concluded that the experimental observations concerning direct bone marrow stimulation by T3 in anephric rats are probably not clinically applicable for the treatment of the anemia associated with uremia.
The Effect of Fine and Coarse Particulate Air Pollution on Mortality: A National Analysis
Authors: Antonella Zanobetti, Joel Schwartz
Journal: Environmental Health Perspectives (2009)

BackgroundAlthough many studies have examined the effects of air pollution on mortality, data limitations have resulted in fewer studies of both particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM2.5; fine particles) and of coarse particles (particles with an aerodynamic diameter &gt; 2.5 and &lt; 10 μm; PM coarse). We conducted a national, multicity time-series study of the acute effect of PM2.5 and PM coarse on the increased risk of death for all causes, cardiovascular disease (CVD), myocardial infarction (MI), stroke, and respiratory mortality for the years 1999–2005.MethodWe applied a city- and season-specific Poisson regression in 112 U.S. cities to examine the association of mean (day of death and previous day) PM2.5 and PM coarse with daily deaths. We combined the city-specific estimates using a random effects approach, in total, by season and by region.ResultsWe found a 0.98% increase [95% confidence interval (CI), 0.75–1.22] in total mortality, a 0.85% increase (95% CI, 0.46–1.24) in CVD, a 1.18% increase (95% CI, 0.48–1.89) in MI, a 1.78% increase (95% CI, 0.96–2.62) in stroke, and a 1.68% increase (95% CI, 1.04–2.33) in respiratory deaths for a 10-μg/m3 increase in 2-day averaged PM2.5. The effects were higher in spring. For PM coarse, we found significant but smaller increases for all causes analyzed.ConclusionsWe conclude that our analysis showed an increased risk of mortality for all and specific causes associated with PM2.5, and the risks are higher than what was previously observed for PM10. In addition, coarse particles are also associated with more deaths.
TCT-559 On-Treatment Platelet Reactivity Testing Before Coronary Artery Bypass Surgery. Does It Predict In-Hospital Major Bleeding?
Authors: Gabriel Sardi, Kenneth Kent, Hironori Kitabata, Joshua Loh, Augusto Pichard, Lowell Satler, William Suddath, Rebecca Torguson, Ron Waksman
Journal: Journal of the American College of Cardiology (2012)