tbuckley/cabot-search huggingface dataset:
Novel Recombinant Interleukin-13 Peptide-based Vaccine Reduces Airway Allergic Inflammatory Responses in Mice
Authors: Yanbing Ma, Kent T. HayGlass, Allan B. Becker, Yijun Fan, Xi Yang, Sujata Basu, Ganesh Srinivasan, F. Estelle R. Simons, Andrew J. Halayko, Zhikang Peng
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Interleukin (IL)-13 plays a pivotal role in the pathogenesis of allergic asthma. Passive administration of its monoclonal antibody or soluble receptor to block overproduced IL-13 has been proven to be effective in controlling airway allergic responses in animal models, but these approaches have disadvantages of short half-lives, high costs, and possible adverse effects.We sought to develop a novel therapeutic strategy through constructing an IL-13 peptide-based vaccine for blocking IL-13 on a persistent effect basis and to evaluate its in vivo effects using a murine model.To break self-tolerance, truncated hepatitis B core antigen was used as a carrier. Vaccine was prepared by inserting a peptide derived from the receptor binding site of mouse IL-13 into the immunodominant epitope region of the carrier using gene recombination methods. Mice received vaccine subcutaneously three times, and then subjected to intraperitoneal sensitization and intranasal challenge with ovalbumin. Control animals received carrier or saline in place of vaccine.The vaccine presented as virus-like particles and induced sustained and high titered IL-13-specific IgG without the use of conventional adjuvant. Vaccination significantly suppressed ovalbumin-induced inflammatory cell number, and IL-13 and IL-5 levels in bronchoalveolar lavage fluids. Serum total and ovalbumin-specific IgE were also significantly inhibited. Moreover, allergen-induced goblet cell hyperplasia, lung tissue inflammatory cell infiltration, and pulmonary hyperresponsiveness to inhaled methacholine were significantly suppressed in vaccinated mice.Our data indicate that IL-13 peptide-based vaccines could be an effective therapeutic approach in the treatment of asthma.
Abstract 9740: Healthy Lifestyle and Leukocyte Telomere Length In U.S. Women
Authors: Qi Sun, Ling Shi, Jennifer Prescott, Stephanie E Chiuve, Frank B Hu, Immaculata De Vivo, Meir J Stampfer, Paul W Franks, JoAnn E Manson, Kathryn M Rexrode
Journal: Circulation (2011)

Objectives: To examine whether healthy lifestyle practices, which are primary prevention measures against major age-related chronic diseases, are associated with longer telomere length. Design: Cross-sectional study. Setting: The Nurses' Health Study, United States. Participants: The population of analysis consisted of 3,355 women who were free of cancer, diabetes, and cardiovascular disease at blood draw in 1990 and were selected as controls in multiple prospective case-control studies within the Nurses' Health Study cohort. Using self-administered questionnaires, these participants provided detailed information on lifestyle practices and dietary habits in 1988 or 1990. Main outcome measures: Z scores of leukocyte telomere length were derived among controls in each case-control study. We defined low-risk categories for five major modifiable factors: non-current smoking, maintaining a healthy body weight (18.5 kg/m2 ≤ body mass index &lt; 24.9 kg/m2), engaging in regular moderate or vigorous physical activities (≥150 minutes/week), drinking alcohol in moderation (1 drink/week to &lt;2 drinks/day), and eating a healthy diet (Alternate Healthy Eating Index score in top 50%). We calculated difference (%) of the z scores contrasting low-risk groups with reference groups to evaluate the association of interest. Results: Although none of the individual low-risk factors was significantly associated with longer leukocyte telomere length z scores, we observed a significant, monotonic relationship between the number of low-risk factors and the z scores. In comparison with women who had no low-risk factors, the leukocyte telomere length z scores were 15.4%, 21.8%, 23.3%, 24.5%, and 33.1% (P for trend = 0.04) higher for women who had 1 to 5 low-risk factors, respectively. Conclusion: Adherence to a healthy lifestyle defined by major modifiable factors may attenuate age-related declines in telomere length.
Abstract 4700: A novel selective EZH2 inhibitor exhibits anti-tumor activity in lymphoma with EZH2 activating mutations
Authors: Caretha L. Creasy, Michael T. McCabe, Susan Korenchuk, Elsie Diaz, Heidi Ott, Christine S. Thompson, Gopi Ganji, Shelby A. Gorman, Louis V. LaFrance, Martin Brandt, Charles McHugh, Sharad K. Verma, Peter J. Tummino
Journal: Cancer Research (2012)

Abstract EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) responsible for methylating histone H3 on lysine 27 (H3K27) and repressing transcription of target genes. Dysregulation of H3K27 methylation is implicated in tumorigenesis in both solid and hematopoietic tumors and occurs through multiple mechanisms including elevation of EZH2 due to loss of regulating miRNAs; inactivating mutations in UTX, an H3K27 demethylase which acts in opposition to EZH2; and somatic mutations in EZH2. Point mutations identified in EZH2 in both follicular lymphoma (FL) and GCB diffuse large B cell lymphoma (DLBCL) exhibit increased H3K27 tri-methylation due to an altered histone substrate preference. This suggests that inhibitors of EZH2 activity may be effective in treating lymphomas carrying activating mutations in EZH2. We have identified first-in-class inhibitors of EZH2 which are highly-potent, reversible, SAM competitive, selective and equipotent against both WT and mutant EZH2. Cellular mechanistic studies demonstrate that inhibition of EZH2 decreases global H3K27me3 in both WT and EZH2 mutant cell lines; however, the cell proliferation response is quite different. Overall, DLBCL cell lines harboring activating mutations in EZH2 are highly sensitive to EZH2 inhibition, while DLBCL cell lines with WT EZH2 are moderately sensitive or resistant. Transcriptional and ChIP-seq studies reveal differences in the transcriptional response of EZH2 target genes and methylation patterns among cell lines providing insight into the mechanism of sensitivity. In a mouse model bearing EZH2 mutant DLBCL tumor xenografts, inhibition of EZH2 methyltransferase activity reduces global H3K27me3, increases expression of EZH2 target genes and inhibits the growth of tumors in a dose dependent manner. Together, these data demonstrate for the first time that direct inhibition of EZH2 methyltransferase activity is effective at inhibiting tumor growth and suggests a promising path forward in the clinic for the treatment of EZH2 mutant lymphoma. 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 4700. doi:1538-7445.AM2012-4700
Primary Liver-Cell Carcinoma With a Protracted Clinical Course
Authors: David D. Hunt
Journal: JAMA (1963)

PRIMARY CARCINOMA of the liver has been described as a rapidly fatal disease. The basis for this prevailing concept has been the uniformly short clinical course in reported cases. The purpose of this paper is to report a case of primary liver-cell carcinoma in a young adult male who survived 5 yr without treatment. <h3>Report of a Case</h3> A 28-yr-old male plasterer entered the Palo Alto-Stanford Hospital on Jan 20, 1962, for evaluation of ascites which had accumulated over a 2-week period. Five years prior to admission, the patient had noted a tender epigastric mass that was estimated to be 9 cm in diameter on physical examination. The mass was thought to be located in the left lobe of the liver. There was no history of hepatitis, alcoholism, or exposure to hepatotoxins. Laboratory tests done at that time included a normal white blood cell count and differential. The serum
Abstract 4973: Long non-coding RNA promotes metastatic behavior in Ewing sarcoma
Authors: Sheetal A. Mitra, Anirban P. Mitra, Jonathan D. Buckley, William A. May, Philipp Kapranov, Robert J. Arceci, Timothy J. Triche
Journal: Cancer Research (2014)

Abstract Ewing sarcoma (ES) is a highly malignant bone and soft tissue tumor with a 20% 5-year survival rate for patients with metastatic disease. Further, even clinically localized tumors are not successfully treated with local therapy like surgery and radiation, indicative of sub-clinical dissemination at presentation, as noted by James Ewing in his original papers. Extensive research has led to better understanding of the molecular pathogenesis of the disease but few discoveries have been successfully translated into improving treatment of ES patients. Our aim is to identify and characterize novel genomic features that can be developed into therapeutic targets for metastatic ES. This study documents the importance of one such ES-specific long non-coding RNA (lncRNA) in invasion and metastasis. Expression data from over a hundred ES primary tumors were compared to normal adult tissues as well as other types of pediatric and adult cancers to identify ES-specific coding and non-coding RNA transcripts. One highly expressed lncRNA, AK057037, was exclusively associated with ES. Further characterization of the transcript using loss of function studies showed that this 2.6 kb, 7 exon, polyadenylated RNA was directly regulated by EWS-FLI1, the chimeric oncoprotein that is the hallmark of ES and a major driver of tumorigenesis. In vitro, knockdown of the lncRNA resulted in reduced invasiveness of ES cells. In vivo, cells over-expressing the transcript showed statistically significant increase in metastasis compared to controls. Downstream targets included cell adhesion molecules such as cadherins and extracellular matrix proteins. Immunoprecipitation (IP) showed binding of the lncRNA to its direct targets. Binding of the lncRNA to other regulatory proteins also affected more global changes including promoter methylation and subsequent modulation of the downstream targets. We conclude that this lncRNA is a highly specific and unique ES biomarker. It acts as an oncogene by promoting invasion and metastasis of ES cells by controlling expression of genes involved in these pathways. Understanding this additional regulation by non-coding RNAs will enable development of multi-modal therapies that may prove to be more effective in treating aggressive disease. Citation Format: Sheetal A. Mitra, Anirban P. Mitra, Jonathan D. Buckley, William A. May, Philipp Kapranov, Robert J. Arceci, Timothy J. Triche. Long non-coding RNA promotes metastatic behavior in Ewing sarcoma. [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 4973. doi:10.1158/1538-7445.AM2014-4973
Medical Groups' Message to Women: If 40 or Older, Get Regular Mammograms
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Medical Groups' Message to Women: If 40 or Older, Get Regular Mammograms Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 15, 2 August 1989, Pages 1126–1128, https://doi.org/10.1093/jnci/81.15.1126 Published: 02 August 1989
Hepatitis B carriage and dental treatment.
Authors: A M Abbas, R A Francis, M D Denton, J H Egan
Journal: BMJ (1981)

anti-inflammatory drugs.2These same authors showed that sulindac does not inhibit frusemide-induced renin release or natriuresis.If it is confirmed that sulindac exerts unique differential inhibition of platelet cyclooxygenase in contrast to the renal enzyme system, large-scale clinical studies should be performed to determine whether sulindac does indeed have a role in those patients who have compromised renal function or in whom diuretic therapy is required.Older patients are particularly at risk and it is in this age group that a non-steroidal anti-inflammatory drug without renal prostaglandin inhibition would be most welcome.
THORACIC AORTIC CALCIFICATION FAILS TO IMPROVE EVENT PREDICTION OVER CORONARY ARTERY CALCIFICATION FOR MYOCARDIAL INFARCTION AND ALL-CAUSE MORTALITY: THE HEINZ NIXDORF RECALL STUDY
Authors: Hagen Kaelsch, Nils Lehmann, Marie Berg, Amir Mahabadi, Stefan Mohlenkamp, Marcus Bauer, Kaffer Kara, Nico Dragano, Susanne Moebus, Karl-Heinz Jöckel, Raimund Erbel
Journal: Journal of the American College of Cardiology (2013)
ERK-Dependent MKP-1–Mediated Cisplatin Resistance in Human Ovarian Cancer Cells
Authors: Juan Wang, Jun-Ying Zhou, Gen Sheng Wu
Journal: Cancer Research (2007)

Abstract Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is the MAPK phosphatase family member that negatively regulates MAPK signaling. Our previous study showed that MKP-1 is involved in cisplatin resistance, but the mechanism underlying its resistance is not understood. Here, we show that ERK2-mediated MKP-1 expression is critical for cisplatin resistance. Specifically, we showed that in the human ovarian cancer cell lines, cisplatin induces MKP-1 through phosphorylation. We also showed that inhibition of ERK2 activity by the MEK1/2 inhibitor U0126 or by small interfering RNA silencing decreases MKP-1 induction, leading to an increase in cisplatin-induced cell death, which mimicked the results obtained with cells in which MKP-1 is down-regulated. Importantly, down-regulation of ERK2 decreased cisplatin-induced MKP-1 phosphorylation, suggesting that MKP-1 phosphorylation depends on ERK2 activity. Furthermore, down-regulation of ERK2 or MKP-1 enhanced cisplatin-induced apoptosis. In addition, we showed that down-regulation of ERK2 or MKP-1 decreases the basal level of Bcl-2 protein and that inhibition of Bcl-2 activity sensitizes ovarian cancer cells to cisplatin. Collectively, our results indicate that induction of MKP-1 by cisplatin is through phosphorylation involving ERK signaling and that MKP-1 plays a critical role in ERK-mediated cisplatin resistance. Thus, our results suggest that targeting ERK-MKP-1 signaling could overcome cisplatin resistance in human ovarian cancer. [Cancer Res 2007;67(24):11933–41]
CASE OF COMPLICATED LABOUR
Authors: H. G. Trend
Journal: BMJ (1856)

white spots in the centre, exactly corresponding with those described in the lung of J. G.Such a state is not rare, but I have never before observed it so intense.If I have not alredy too far trespassed upon your space, I will add a few particulars of a case of malposition of the heart.L. W., aged 22, was admitted an out-patient in October.She complained; of much palpitation and shortness of breath.Is a tall girl, with dark hair and eyes, sallow; changes colour often, and is very subject to throbbing headache and giddiness, with pain in the eyes.Catamenia regular; never swells in abdomen or limbs; sleeps well, but starts and dreams much.On examination, I found the chest slightly bulged on the right side.The heart's im pulse isible under the second, third, fourth, and fifth ribs, on the right side of the sternum.There was a loud bruit under the left sterno-clavicular articulation, with dulness over the front and back of the right chest.She first no- ticed "the beating" on the right side three yeas ago; it became excessive twelve months since, when she was treated and relieved by Dr. W. Budd in the infirmary.It is now bcoming, however, as bad as ever.She is unable to afford any further particulars, and is now under treatment, but so far relieved as to be free from uneasiness, unless after sudden exertion.
Esophageal cancer: The precursors (Part II)
Authors: R. Lambert, P. Hainaut
Journal: Endoscopy (2007)

The epidemiology of esophageal cancer has been considered in part I of this review [1]. Squamous cell carcinoma (SCC), accounts for the majority of cases, which tend to occur in low-resource countries, particularly in certain regions of Asia, where the age-standardized rate (ASR) incidence can be higher than 100/100 000). Adenocarcinoma (ADC) is less frequent and develops from a metaplastic epithelium. The ASR incidence of ADC is higher in Caucasians and in men, but is still low at less than 5 in men and 1 in women; however it is increasing rapidly in the USA, Australia, and northern Europe, and may have a significant impact in the near future.
Arterial Hypoxemia and Pulmonary Blood Flow in Myocardial Infarction.
Authors: H. Kazemi
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971Arterial Hypoxemia and Pulmonary Blood Flow in Myocardial Infarction.H. Kazemi, M.D., F.A.C.P., F. Al Bazzaz, M.D.H. Kazemi, M.D., F.A.C.P.Search for more papers by this author, F. Al Bazzaz, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-820_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptRegional distribution of pulmonary blood flow and ventilation was determined at the bedside in the sitting position in patients within 5 days after myocardial infarction or hospitalization because of angina and 3 months after recovery from infarction. Distribution studies were performed with133Xe and15O-labeled O2and CO2. Cardiac output, arterial blood gases, and pulmonary gas exchange were also measured. All subjects were free of cardiorespiratory symptoms at the time of study, and none showed evidence of congestive failure on examination. Marked hypoperfusion of lung base was found in patients after acute myocardial infarction, which reverted towards normal in the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Mass. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 820-820KeywordsAcute myocardial infarctionAnginaBloodBlood flowCardiac outputHospitalizationsHypoxiaInfarctionLungsMyocardial infarction Issue Published: 1 May 1971 PDF DownloadLoading ...
Alpha and beta adrenergic effects on human atrial specialized conducting fibers.
Authors: L Mary-Rabine, A J Hordof, F O Bowman, J R Malm, M R Rosen
Journal: Circulation (1978)

We determined the effects of epinephrine on automaticity and action potential characteristics of right atrial specialized fibers (RAF) from human atria obtained during cardiac surgery. RAF were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. A biphasic response to epinephrine was seen, rate slowing at low agonist concentrations and increasing at high concentrations. The epinephrine-induced slowing of spontaneous rate was due to a decrease in the slope of phase 4 depolarization. At the high epinephrine concentrations RAF hyperpolarized. The alpha-adrenergic blocker, phentolamine, shifted the dose-response curve upward and to the left and enhanced the hyperpolarization of RAF. The beta blocker, propranolol, shifted the curve to the right and decreased the degree of hyperpolarization. Our study suggests the presence of alpha and beta receptors in RAF. The alpha response consists of a slowing of rate, the beta response of an acceleration of rate and hyperpolarization of RAF.
Nubile Maidens and the Premarital Law
Authors: S. W. Trythall
Journal: JAMA (1964)

<h3>To the Editor:—</h3> The attainment of reasonable law and order as an objective in life is commonly accepted. Since man emerged from the caves, it has been necessary to impose certain rules on individuals in order to further the well-being of society. In support of controls in public health, I can offer no better example than Michigan Department of Health statistics (June 23, 1964). In 1947 there were 111 syphilitic babies born in the state. In 1956 there were only two such births, testing of every new mother being required by law. In 1963 there were 11, indicative of the national increase in syphilis. The report shows further that in 1950 there were 20 infant deaths from the disease, while in 1962 there was only 1. Improved controls in detection and therapy assuredly benefit the public as well as the newborn. Would not Dr. Magill admit that these facts justify
Cutaneous lymphocyte antigen and α4β7 <scp>T</scp>‐lymphocyte responses are associated with peanut allergy and tolerance in children
Authors: S. M. H. Chan, V. Turcanu, A. C. Stephens, A. T. Fox, A. P. Grieve, G. Lack
Journal: Allergy (2012)

Abstract Background: It is unclear whether the initial route of allergen exposure in early life could influence the subsequent development of allergy, with cutaneous sensitization leading to peanut allergy ( PA ), and tolerance induced by oral exposure. The skin‐ and gastrointestinal ( GI )‐homing markers, cutaneous lymphocyte antigen ( CLA ) and α4β7 integrin, are used to determine whether the state of PA correlates with peanut‐specific CLA responses, with tolerance associated with predominant α4β7 responses. Methods: CLA + and α4β7+ memory T cells were isolated and cultured with peanut extract to assess their proliferation. Stimulation indices were compared in peanut allergic and non‐allergic ( NA ) groups, and peanut‐specific cytokine production was measured. Results: In peanut allergic patients, peanut‐specific proliferation predominates in the skin‐homing CLA + subset, whilst peanut‐tolerant groups have a mixed CLA /α4β7 response ( P = 0.008). Comparison with a control food antigen (ovalbumin) showed that these differences are allergen specific. Cytokine responses showed trends towards Th1 skewing in the GI ‐homing α4β7+ cells of peanut‐tolerant groups and Th2 skewing in the skin‐homing CLA + cells of peanut allergic patients. Conclusion: The predominance of the CLA + response to peanut in peanut allergic patients is consistent with the hypothesis that allergic sensitization occurs through the skin. The predominant α4β7+ response in peanut‐tolerant groups suggests that allergen exposure through the GI tract induces tolerance.
REPORT OF A DEATH FROM CHLOROFORM ANESTHESIA, BEING THE FIRST IN A PRACTICE OF SIXTEEN YEARS, AND INCLUDING NOT LESS THAN TWO THOUSAND CHLOROFORM ANESTHESIAS.
Authors: BAYARD HOLMES
Journal: JAMA (1902)

It is my unpleasant duty to report the first death from chloroform in my practice, not a very large one to be sure, which began in the Cook County Hospital in 1885. I have not kept a record of the number of anesthetics given for me, but they have certainly not been less than two hundred a year. Chloroform has been uniformly used. Only when a patient insisted on ether has anything but chloroform been given. It has been my practice to have a skilful person administer the chloroform, even if it necessitated an untried and even inexperienced physician as my first assistant. My anesthetizers have been trained by me to give chloroform on two thicknesses of cheesecloth held over the left index finger or spread on a wire mask. It is administered drop by drop from an ounce bottle with a little notch cut out of the side of
Weak evidence for a strong case against modularity in developmental disorders
Authors: Ralph-Axel Müller
Journal: Behavioral and Brain Sciences (2002)

Thomas &amp; Karmiloff-Smith (T&amp;K-S) provide evidence from computational modeling against modular assumptions of “Residual Normality” (RN) in developmental disorders. Even though I agree with their criticism, I find their choice of empirical evidence disappointing. Cognitive neuroscience cannot as yet provide a complete understanding of most developmental disorders, but what is known is more than enough to debunk the idea of RN.