tbuckley/cabot-search huggingface dataset:
Abstract 336: 4-methylumbeliferone, an HA synthesis inhibitor, inhibits EMT determinants in bladder cancer cell lines
Authors: Travis Yates, Mike Garcia-Roig, Muthu K. Veerapen, Anaid Benitez, Vinata Lokeshwar
Journal: Cancer Research (2012)

Abstract INTRODUCTION AND OBJECTIVE: Elevated Hyaluronic Acid (HA) levels are a molecular determinant of bladder cancer (BCa) metastasis. Furthermore, HA, HYAL-1 hyaluronidase and HA-synthesizing enzymes are potential markers for BCa diagnosis and predicting prognosis. 4-Methylumbelliferone (4-MU) is an orally bioavailable dietary supplement that inhibits HA synthesis. Epithelial mesenchymal transition (EMT) is the hallmark of invasion and metastasis, in which cancer cells acquire an invasive phenotype. Since HA promotes tumor metastasis, we evaluated the antitumor effects of 4-MU in vitro and in vivo and examined whether 4-MU can reverse the EMT by inhibiting HA synthesis. METHODS: Quantitative PCR was used to measure mRNA expression of EMT genes (β-catenin, Twist, and Snail) in 66 bladder tissue specimens (27 normal; 39 tumor); follow-up: 26±4.3 months; median 20 months. The effect of 4-MU (0.2 - 0.6 mM) on cell proliferation, apoptosis, intracellular signaling, and the expression of HA receptors and EMT genes were examined in BCa cell lines, 253J-Lung and HT1376. Effect of 4-MU on tumor growth was analyzed in subcutaneous xenografts. RESULTS: Among the EMT genes, both Snail and Twist were differentially expressed in BCa tissues when compared to normal bladder (P&amp;lt;0.001). Furthermore, Twist expression significantly correlated with metastasis (+: 0.25+0.15, -: 0.12+0.14; P=0.028). β-catenin expression negatively correlated with survival (chi square=4.3, p=0.038). 4-MU inhibited proliferation and induced apoptosis in the BCa cells. Following a 48 h exposure at the IC50 for HA synthesis (0.4 mM), 4-MU inhibited proliferation by 61% and increased apoptosis by 73%. 4-MU induced caspase-8, -9 and -3 activation and up-regulation of Fas and FADD. 4-MU downregulated the expression of HA-receptors - CD44, RHAMM, EMT promoters - β-catenin, Snail and Twist by 4-10-fold, but increased the expression of E-cadherin by 2-fold, suggesting EMT-reversal. In xenograft studies, 4-MU significantly decreased tumor growth (&amp;gt; 3-fold) when treatment was started either on the day of tumor cell injection or after tumors became palpable. No weight loss or serum or organ toxicity was observed in treated mice. Tumors showed reduced microvessel density (∼3-fold) and HA expression but increased TURNEL positive cells. CONCLUSION: This is the first study that shows inhibition of HA synthesis by an orally bioavailable, non-toxic supplement potentially reverses EMT and has potent anti-tumor activity. Support: R01 CA 123063-04 (VBL); R01 CA 72821-11 (VBL). 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 336. doi:1538-7445.AM2012-336
THE DISCOVERER OF THE MODE OF PRODUCTION OF BREATH SOUNDS
Authors: G. E. BUSHNELL
Journal: JAMA (1923)

In an article recently published inThe Journal, I<sup>1</sup>reported the discovery that it was possible to abolish all breath sounds as heard over the larynx and the chest by a voluntary separation of the vocal cords. The discovery was entirely original on my part, yet it seemed incredible that so simple and easy a procedure as the voluntary widening of the rima glottidis should never have occurred to any one until the present time. A search through the literature now shows that I had been anticipated by nearly a century. At the session of the Académie royale de médecine, June 10, 1834, Beau<sup>2</sup>described a case in which he heard a very marked bronchial souffle at the level of the subspinous fossa, in a patient with "effusion of the right pleura" who was breathing noisily. Wishing to know how much the noise of respiration contributed to produce
ROENTGENTHERAPY IN CANCER OF THE HYPOPHARYNX
Authors: FRANCOIS BACLESSE
Journal: JAMA (1949)

The prognosis for cancer of the hypopharynx is poor because tumors occurring in this site are usually of an ulcerating and destructive nature. Complications, such as infection, involvement of the cartilage and sometimes considerable extension to the surrounding structures, make these lesions difficult to cure. <h3>ANATOMIC CLASSIFICATION</h3> The upper or membranous portion of the hypopharynx includes the whole aryepiglottic fold and the thyrohyoid membrane. The upper limit is the pharyngoepiglottic fold and the lower limit, approximately, the mucous fold of the superior laryngeal nerve. Radiographically, this part is projected between the hyoid bone and the superior border of the thyroid cartilage. The lower or osteocartilagenous portion of the hypopharynx is deep, narrow and hidden. It is limited laterally by the thyroid lamina and medially by the arytenoid and the cricoid cartilages covered by muscles and fascia. The distinction between the two parts is of particular significance when one considers the
The pulsed Doppler coronary artery catheter preliminary report of a new technique for measuring rapid changes in coronary artery flow velocity in man.
Authors: J S Cole, C J Hartley
Journal: Circulation (1977)

A new catheter which measures instantaneous changes in coronary artery blood flow velocity is described. The linear relationship between flow velocity is described. The linear relationship between flow velocity measured with the catheter and volume flow through small arteries is documented with a correlation coefficient of 4=0.99. Coronary flow velocity has been measured from the proximal right and left coronary arteries and aortic ostia of saphenous vein bypass grafts in patients undergoing diagnostic coronary arteriography. The increase in coronary flow following injection of contrast media in normal coronary arteries is similar to the increase in coronary flow reported following near-maximum exercise. This increased flow response following injection of contrast media is severly limited by coronary artery stenosis and may provide a useful method for assessing hemodynamically significant stenosis in patients with coronary artery disease.
Comparison of the Short-Term Survival Benefit Associated With Revascularization Compared With Medical Therapy in Patients With No Prior Coronary Artery Disease Undergoing Stress Myocardial Perfusion Single Photon Emission Computed Tomography
Authors: Rory Hachamovitch, Sean W. Hayes, John D. Friedman, Ishac Cohen, Daniel S. Berman
Journal: Circulation (2003)

Background— The relationship between the amount of inducible ischemia present on stress myocardial perfusion single photon emission computed tomography (myocardial perfusion stress [MPS]) and the presence of a short-term survival benefit with early revascularization versus medical therapy is not clearly defined. Methods and Results— A total of 10 627 consecutive patients who underwent exercise or adenosine MPS and had no prior myocardial infarction or revascularization were followed up (90.6% complete; mean: 1.9±0.6 years). Cardiac death occurred in 146 patients (1.4%). Treatment received within 60 days after MPS defined subgroups undergoing revascularization (671 patients, 2.8% mortality) or medical therapy (MT) (9956 patients, 1.3% mortality; P =0.0004). To adjust for nonrandomization of treatment, a propensity score was developed using logistic regression to model the decision to refer to revascularization. This model (χ 2 =1822, c index=0.94, P &lt;10 −7 ) identified inducible ischemia and anginal symptoms as the most powerful predictors (83%, 6% of overall χ 2 ) and was incorporated into survival models. On the basis of the Cox proportional hazards model predicting cardiac death (χ 2 =539, P &lt;0.0001), patients undergoing MT demonstrated a survival advantage over patients undergoing revascularization in the setting of no or mild ischemia, whereas patients undergoing revascularization had an increasing survival benefit over patients undergoing MT when moderate to severe ischemia was present. Furthermore, increasing survival benefit for revascularization over MT was noted in higher risk patients (elderly, adenosine stress, and women, especially those with diabetes). Conclusions— Revascularization compared with MT had greater survival benefit (absolute and relative) in patients with moderate to large amounts of inducible ischemia. These findings have significant consequences for future approaches to post–single photon emission computed tomography patient management if confirmed by prospective evaluations.
HEART RATE VARIABILITY AND THE SUBSTRATE FOR VENTRICULAR TACHYCARDIA IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY
Authors: Pasquale Santangeli, Antonio Dello Russo, Michela Casella, Gemma Pelargonio, Luigi Di Biase, Pietro Santarelli, Stefano Bartoletti, Rong Bai, Prasant Mohanty, Sanghamitra Mohanty, Agnes Pump, Andrea Natale
Journal: Journal of the American College of Cardiology (2012)
Probilin—A Criticism and a Reply.
Authors: None Schering
Journal: JAMA (1907)

New York City, Oct. 5, 1907. <h3>To the Editor:</h3> —Our delay in replying to the "Report on Probilin by the Council on Pharmacy and Chemistry—with Comments," published in your issue of Aug. 24, 1907, was occasioned by the fact that we awaited the advices of the general agents for Probilin, Messrs. Goedecke &amp; Co., in Leipsic, who in turn communicated with the manufacturer, F. Buchka, in Frankfort o/M. It is regrettable that you reached and published these findings without having informed us of them; without having given us an opportunity to submit evidence in rebuttal and to show wherein both "Report" and "Comments" are wholly incorrect. This method of procedure, which has committed you to a wrong position, was arbitrary and injudicial. It is manifestly absurd to suppose that a firm would give a formula knowing that it calls for a weight greater than that which the product actually possesses,
EU law forces UK ministers to rethink food labelling
Authors: Z. Kmietowicz
Journal: BMJ (2012)

Health ministers from the four countries of the United Kingdom have launched a consultation on what system food manufacturers should use to show consumers the nutritional content of products.

The move comes after the European Union passed legislation last July designed to improve the clarity and degree of information provided on food packaging across the EU.1

The new rules make it compulsory for the first time for food labels to include details of the energy, protein, fat, saturated fat, carbohydrate, sugar, and salt levels. The rules took three years to agree, and the parts concerning labelling come into force in 2016.

John Dalli, the EU health and consumer commissioner, …
Hemodynamic Effects of Nitrous Oxide Administered During Cardiac Catheterization
Authors: Joshua Wynne
Journal: JAMA (1980)

To assess the effects of nitrous oxide on hemodynamics and left ventricular function in man, 30 patients (24 of whom had coronary artery disease) were studied at the time of cardiac catheterization. Left ventricular peak-systolic pressure and end-diastolic volume showed no significant change during nitrous oxide inhalation. The maximum rate of pressure rise declined slightly, but left ventricular end-diastolic pressure and ejection fraction were unchanged. Heart rate and cardiac index declined modestly. The pressure-rate product and left ventricular minute work index decreased, suggesting a decline in myocardial oxygen requirements. These data suggest that nitrous oxide inhalation does not produce important depression of left ventricular performance. The consistent decrease in the determinants of myocardial oxygen demand suggests that use of this analgesic agent may be helpful in patients with coronary heart disease. (<i>JAMA</i>243:1440-1443, 1980)
Improved Long-Term Survival After Abdominal Aortic Aneurysm Repair
Authors: Kevin Mani, Martin Björck, Jonas Lundkvist, Anders Wanhainen
Journal: Circulation (2009)

Treatment of abdominal aortic aneurysm (AAA) has changed significantly over the past 2 decades. In this perspective, time trends in long-term survival were studied.We identified 8663 primary intact and 4171 ruptured AAA repairs in the Swedish Vascular Registry from 1987 to 2005. Mortality was obtained from the national population registry. Crude survival was analyzed, including all mortality. To analyze the long-term outcome among those surviving the AAA repair, relative survival, which denotes the survival rate of patients compared with that of the general population adjusted for age, sex, and calendar year, was calculated, excluding 90-day mortality. In a comparison of AAA repairs from 1987 to 1999 and 2000 to 2005, age (71.4 versus 72.5 years; P<0.001), patients with comorbidities (65.0% versus 68.5%; P<0.001), and endovascular repair (1.6% versus 17.0%; P<0.001) increased. After intact AAA repair, crude 5-year survival was 69.0% (99% confidence interval [CI], 67.7 to 70.4), and relative 5-year survival excluding 90-day mortality was 90.3% (99% CI, 88.6 to 92.0). Relative 5-year survival was better for those operated on from 2000 to 2005 compared with 1987 to 1999 (difference, 4.7%; 99% CI, 1.3 to 8.1), for men versus women (4.6%; 99% CI, 0.4 to 8.8), and for octogenarians versus patients <80 years of age (10.2%; 99% CI, 1.5 to 18.8); no difference was observed between open and endovascular repair (6.0%; 99% CI, -1.5 to 13.4). After ruptured AAA repair, crude 5-year survival was 41.7% (99% CI, 39.6 to 43.7) and relative 5-year survival was 87.1% (99% CI, 83.9 to 90.3). No significant differences in relative 5-year survival were observed between time periods, sex, or age groups.Long-term survival improved over time after intact AAA repair despite a change in case mix toward older patients with more comorbidities. Long-term survival was stable after ruptured AAA repair.
A New Diabetic Chart
Authors: P. L. Robinson, E. T. Baker-Bates
Journal: BMJ (1952)

cause.There is already apparent some tendency to adopt such an attitude, and even to look upon it as yet one more example of failure -of bodily adaptation to stress (Selye, 1951).As to its treatment, recent reports of initial success with cortisone or A.C.T.H. (Siltzbach et al., 1951; Lovelock and Stone, 1951; Small, 1951) are encouraging, but it is too early yet to assess their real value.No remedy used in the past has proved of an unequivocal value.Summary Neurological complications in sarcoidosis are occa- sionally met with, more commonly in the uveoparotid form of the disease than in other variants.Most often they are of the peripheral neuritic type, but disorder of central nervous function also occurs, with symptomato- logy proper to the region involved.Four clinical case records are presented by way of example.Sarcoid lesions in the nervous system, whether in nerves or cerebrospinal axis, are the same in histological struc- ture as those seen in other tissues, and, like the latter, presumably represent reaction of indigenous mesenchy- mal elements to whatever may be the cause (or causes) of the syndrome of sarcoidosis.
Child Abuse and Children's Advocates, Inc
Authors: Helene Tanous
Journal: JAMA (1979)

To the Editor.—  I am writing regarding the excellent article Who Needs Counseling in Child Abuse? by B. J. M. (242:132, 1979). The lack of protection for abused children in the United States is scandalous. They are frequently returned to dangerous environments by governmental agencies, hospitals, or physicians without legal representation, where they are the victims of repeated acts of cruelty. These children are crying out in anguish for help.  In the United States there are an estimated 1 million cases of child abuse, and 4,000 deaths occur annually. Many severely abused children suffer permanent physical injury, and of those returned to their environment, at least 10% die. According to a Department of Health, Education, and Welfare official, the plight of the majority of children who die from abusive treatment was previously known to some form of authority before the deaths.  A revealing report by Berkeley Planning Associates, funded by
Monoclonal T-Cell Receptors: New Reagents for Cancer Therapy
Authors: Hans J Stauss, Michela Cesco-Gaspere, Sharyn Thomas, Daniel P Hart, Shao-An Xue, Angelika Holler, Graham Wright, Mario Perro, Ann-Margaret Little, Constantina Pospori, Judy King, Emma C Morris
Journal: Molecular Therapy (2007)

Adoptive transfer of antigen-specific T lymphocytes is an effective form of immunotherapy for persistent virus infections and cancer. A major limitation of adoptive therapy is the inability to isolate antigen-specific T lymphocytes reproducibly. The demonstration that cloned T-cell receptor (TCR) genes can be used to produce T lymphocyte populations of desired specificity offers new opportunities for antigen-specific T-cell therapy. TCR gene-modified lymphocytes display antigen-specific function in vitro, and were shown to protect against virus infection and tumor growth in animal models. A recent trial in humans demonstrated that TCR gene-modified T cells persisted in all and reduced melanoma burden in 2/15 patients. In future trials, it may be possible to use TCR gene transfer to equip helper and cytotoxic T cells with new antigen-specificity, allowing both T-cell subsets to cooperate in achieving improved clinical responses. Sequence modifications of TCR genes are being explored to enhance TCR surface expression, while minimizing the risk of pairing between introduced and endogenous TCR chains. Current T-cell transduction protocols that trigger T-cell differentiation need to be modified to generate "undifferentiated" T cells, which, upon adoptive transfer, display improved in vivo expansion and survival. Both, expression of only the introduced TCR chains and the production of naïve T cells may be possible in the future by TCR gene transfer into stem cells.
Should We Treat `Mild' Hypertension?
Authors: Neil Harding McAlister
Journal: JAMA (1983)

MILD, essential hypertension has been defined as the "gray zone" between normal BP and essential hypertension that clearly warrants treatment.<sup>1</sup>While many agree that in adults diastolic BP (DBP) below 90 mm Hg is "normal," this upper limit is artificial. The Framingham study has been interpreted as showing a linear relationship between the subsequent development of cardiovascular disease and baseline DBP over 60 mm Hg<sup>2</sup>(although this interpretation has been disputed).<sup>3</sup>Normal DBP depends on age, sex, and race; but the use of 90 mm Hg as the universal upper limit of normotension seems safe and utilitarian. Defining the lower limit of DBP that clearly demands treatment is even more difficult. The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommends that all patients with a DBP of 105 mm Hg or greater be treated.<sup>4</sup>The clinical effectiveness of treating such patients was shown
Trial of oral miltefosine for visceral leishmaniasis
Authors: Shyam Sundar, Frank Rosenkaimer, Manoj K Makharia, Ashish K Goyal, Ashim K Mandal, Andreas Voss, Peter Hilgard, Henry W Murray
Journal: The Lancet (1998)

Background There is no effective oral treatment for visceral leishmaniasis (kala-azar), a disseminated intracellular protozoal infection that occurs worldwide. Miltefosine, an alkyl phospholipid developed as an oral antineoplastic agent, is active against visceral infection in animal models. We tested safety, tolerance, and efficacy of miltefosine in kalaazar. Methods Oral doses of miltefosine were given to six groups of five Indian men for 28 days: 50 mg every second day (group 1), 100 mg every second day (group 2), 100 mg/day (group 3), 150 mg/day (group 4), 200 mg/day (group 5), and 250 mg/day (group 6). Assessment for apparent cure—taken as an afebrile state with decreased spleen size and a splenic-aspirate parasite-density score of 0-was done on days 14 and 28. Definitive cure at 8 months required a parasite-free bone-marrow aspirate and no clinical evidence of relapse. Findings 21 of 30 patients were apparently cured on day 14. Transient episodes of vomiting and diarrhoea, were common during weeks 1–2 and were seen in 22 patients. Four other patients in groups 5 and 6 had miltefosine withdrawn after 7–10 days because of vomiting. One patient in group 6 developed renal insufficiency and severe diarrhoea and died on day 21. On day 28, all 29 remaining patients were apparently cured. By 8 months, seven of ten patients in groups 1 and 2 had relapsed; however, 18 of 19 patients treated daily (groups 3–6) appeared to be cured. Among the 21 definitive cures were the four patients treated for 10 days or less and 12 for whom previous therapy with pentavalent antimony had failed. Interpretation Treatment with miltefosine at 100–150 mg/day for 4 weeks has promise as an effective oral treatment of visceral leishmaniasis including antimonyresistant infection.
Prevalence of asthma in Melbourne schoolchildren: changes over 26 years.
Authors: C F Robertson, E Heycock, J Bishop, T Nolan, A Olinsky, P D Phelan
Journal: BMJ (1991)

OBJECTIVES--To determine the prevalence of asthma in the past 12 months in Melbourne schoolchildren aged 7, 12, and 15 years and to compare the prevalence of a history of asthma with that of 26 years ago. DESIGN--A questionnaire on respiratory symptoms was distributed to children for completion by parents and return to the school. Subjects were selected by a stratified cluster design. SETTING--Government and non-government schools in the greater Melbourne area, Australia. SUBJECTS--10,981 children. Parents completed questionnaires for 3324 children aged 7, 2899 aged 12, and 2968 aged 15. The overall response rate was 90%. MAIN OUTCOME MEASURES--History of wheeze or asthma in the past 12 months and in lifetime. RESULTS--The prevalences of wheeze in the past 12 months were 23.1%, 21.7%, and 18.6% for 7, 12, and 15 year olds respectively. A history of wheeze was more common in boys than in girls at age 7 (443/1711 v 324/1614) and 12 (418/1767 v 322/1718) but not at age 15. Overall, 78% (1548) of those reporting wheeze also reported a history of asthma and 83% (1611) had used a bronchodilator. The prevalence of a history of asthma among 7 year olds was 46% compared with 19.1% in the 1964 survey, an increase of 141%. CONCLUSIONS--The current prevalence of asthma in Melbourne schoolchildren is high and has risen substantially over the past 26 years.
Influence of different collagen species on physico-chemical properties of crosslinked collagen matrices
Authors: Peter Angele, Jochen Abke, Richard Kujat, Hubert Faltermeier, Detlef Schumann, Michael Nerlich, Bernd Kinner, Carsten Englert, Zbigniew Ruszczak, Robert Mehrl, Rainer Mueller
Journal: Biomaterials (2003)
SCG/Kinjoh mice: A model of ANCA-associated crescentic glomerulonephritis with immune deposits
Authors: Irmgard Neumann, Rainer Birck, Mark Newman, Peter Schnülle, Wilhelm Kriz, Kyuichi Nemoto, Benito Yard, Rüdiger Waldherr, Fokko J. Van Der Woude
Journal: Kidney International (2003)