tbuckley/cabot-search huggingface dataset:
Treatment of Hematologic Malignancies with Immunotoxins and Antibody-Drug Conjugates
Authors: David J. FitzGerald, Alan S. Wayne, Robert J. Kreitman, Ira Pastan
Journal: Cancer Research (2011)

Abstract To enable antibodies to function as cytotoxic anticancer agents, they are modified either via attachment to protein toxins or highly potent, low-molecular-weight drugs. Such molecules, termed immunotoxins and antibody-drug conjugates, respectively, represent a second revolution in antibody-mediated cancer therapy. Thus, highly toxic compounds are delivered to the interior of cancer cells based on antibody specificity for cell-surface target antigens. Cancer Res; 71(20); 6300–9. ©2011 AACR.
Evaluation of left ventricular function during upright exercise: correlation of exercise Doppler with postexercise two-dimensional echocardiographic results.
Authors: A A Mehdirad, G A Williams, A J Labovitz, R J Bryg, B R Chaitman
Journal: Circulation (1987)

The relationship of regional and global left ventricular function to aortic flow dynamics during exercise was determined in 14 normal subjects and 14 patients with coronary artery disease. Doppler and two-dimensional echocardiographic studies were performed before, during, and immediately after an exercise test by the Bruce protocol. Two-dimensional echocardiography was used to determine the ejection fraction and new wall motion abnormalities. The peak ejection velocity, stroke index, and cardiac index were calculated from the pulsed Doppler tracing. In normal subjects the ejection fraction increased significantly (p less than .001) from rest (0.51 +/- 0.07) to peak exercise (0.61 +/- 0.07), while the response in coronary patients was blunted (0.49 +/- 0.11 vs 0.48 +/- 0.16). Similarly, the change in peak ejection velocity throughout exercise in normal subjects (from 0.71 +/- 0.12 to 1.50 +/- 0.35 m/sec) was significantly (p less than .01) greater than that in patients with coronary artery disease (from 0.61 +/- 0.13 to 0.90 +/- 0.29 m/sec). There was a good correlation between the percent change in peak ejection velocity and the percent change in ejection fraction from rest to peak exercise in the entire study group (rs = .64) and in the patients with coronary artery disease (rs = .84). These preliminary data suggest that exercise-induced changes in Doppler echocardiographic variables may offer a potential adjunct in the evaluation of patients with ischemic heart disease.
Transduction of bacteriocin determinants in group A streptococci.
Authors: J R Tagg, S Skjold, L W Wannamaker
Journal: The Journal of Experimental Medicine (1976)

Determinants of streptococcin A-FF22 (SA) production and host cell immunity have been transduced to three serologically distinct Group A streptococci. Streptomycin resistance markers were not cotransducible with bacteriocin determinants. SA+ transductants of strains unrelated to the parent SA+ strain were unstable but SA+ transductants of a spontaneous SA- derivative of the parent appeared to be stable.
The Ras Activator RasGRP3 Mediates Diabetes-Induced Embryonic Defects and Affects Endothelial Cell Migration
Authors: Paramjeet K. Randhawa, Svetlana Rylova, Jessica Y. Heinz, Stephanie Kiser, Joanna H. Fried, William P. Dunworth, Amanda L. Anderson, Andrew T. Barber, John C. Chappell, David M. Roberts, Victoria L. Bautch
Journal: Circulation Research (2011)

Fetuses that develop in diabetic mothers have a higher incidence of birth defects that include cardiovascular defects, but the signaling pathways that mediate these developmental effects are poorly understood. It is reasonable to hypothesize that diabetic maternal effects are mediated by 1 or more pathways activated downstream of aberrant glucose metabolism, because poorly controlled maternal glucose levels correlate with the frequency and severity of the defects.
Increased sensitivity for the detection of malignant melanoma cells in peripheral blood using an improved protocol for reverse transcription?polymerase chain reaction
Authors: None Schittek, None Blaheta, None FLÖrchinger, None Sauer, None Garbe
Journal: British Journal of Dermatology (1999)

Conflicting results have been obtained by various research groups using tyrosinase reverse transcription–polymerase chain reaction (RT–PCR) for detecting micrometastases in the blood of melanoma patients, with positive results ranging from 0 to 100% in disseminated melanoma. Methodological differences in the processing of blood samples may in part account for these discrepancies. The aim of this study was to standardize and optimize the experimental conditions for RT–PCR detection of melanoma cells in peripheral blood. We analysed the effect of different parameters of sample processing on the sensitivity of the tyrosinase RT–PCR using peripheral blood spiked with defined numbers of SKMEL28 melanoma cells. Purification of the mononuclear cell fraction using a Ficoll gradient with a density of 1.077 g/mL prior to RNA isolation gave the highest sensitivity, with the detection of two SKMEL28 cells in 5 mL of blood. In addition, the RNA isolation method and the kind of RT enzyme used had a significant impact on the sensitivity and reproducibility of tyrosinase detection, whereas variations in the PCR conditions had only a minor influence. Furthermore, we showed that amplification of MelanA in addition to tyrosinase resulted in an approximately 10% enhanced sensitivity of melanoma cell detection, whereas gp100/pMel17 and MUC18 gene products were also detected in blood from non-melanoma patients. MelanA could serve as a sensitive marker in addition to tyrosinase for detecting micrometastases.
Conventional and chest-compression-only cardiopulmonary resuscitation by bystanders for children who have out-of-hospital cardiac arrests: a prospective, nationwide, population-based cohort study
Authors: Tetsuhisa Kitamura, Taku Iwami, Takashi Kawamura, Ken Nagao, Hideharu Tanaka, Vinay M Nadkarni, Robert A Berg, Atsushi Hiraide
Journal: The Lancet (2010)
Porcine intestinal adenomatosis: epithelial dysplasia and infiltration.
Authors: L Roberts, A C Rowland, G H Lawson
Journal: Gut (1980)

Occasionally in cases of porcine intestinal adenomatosis (PIA) epithelial dysplasia is seen with infiltration of the epithelium into underlying tissues and spread, via the lymphatics, to drainage lymph nodes. The intracellular bacterium Campylobacter sputorum subspecies mucosalis, associated with PIA, can be demonstrated in the epithelial cells of the metastases. This dysplasia and infiltration appears to be related to surface damage and inflammation.
Pyothorax-associated lymphoma: relationship with Epstein-Barr virus, human herpes virus-8 and body cavity-based high grade lymphomas
Authors: P Taniere, A Manai, R Charpentier, P Terdjman, S Boucheron, JF Cordier, F Berger
Journal: European Respiratory Journal (1998)

Pyothorax-associated lymphoma (PAL) is a newly-described entity developing several decades after artificial pneumothorax treatment for pulmonary or pleural tuberculosis. It is known to be associated with Epstein-Barr virus (EBV) with constant expression of the two latent membrane proteins: latent membrane protein (LMP)-1 and EBV-associated nuclear antigen (EBNA)-2. We are reporting three new cases of PAL. All of the tumours were of B-cell lineage and classified as large-cell diffuse lymphomas according to the International Working Formulation for the Classification of Lymphomas. The EBV genome was detected in two of the cases with LMP-1 and EBNA-2 expression. No EBV could be detected in the third case suggesting that different mechanisms may be involved in the pathogenesis of the disease. Body cavity-based high grade lymphomas (BCBL) represent a new disease, developing mainly in human immunodeficiency virus (HIV) infected patients: the tumoural cells often contain both human herpes virus (HHV)-8 (or Kaposi's sarcoma herpes virus) and EBV genomes, suggesting that these viruses might co-operate in the pathogenesis of the disease. The pleural location and the association of EBV have led to speculation that PAL could also be related to HHV-8 infection. However, no HHV-8 genome could be detected in any of the 14 tested cases already reported in the literature nor in the two cases we studied (one EBV-positive and one EBV-negative), suggesting that PAL and BCBL are two different entities.
OC-048 Adenoma detection reduces during a colonoscopy list
Authors: R Gao, G D Corbett, J Lee, F Sampaziotis, E Cameron
Journal: Gut (2012)

<h3>Introduction</h3> Recent studies have provided conflicting data on whether colonoscopy lesion detection varies with time of day.<sup>1–3</sup> We aimed to assess whether the time of procedure within a list affected polyp and adenoma detection rate (PDR, ADR), surrogate markers for colonoscopy quality, at a busy tertiary centre endoscopy unit in the UK. <h3>Methods</h3> All patients undergoing colonoscopy in 2009 were retrospectively identified and included in the study. Patient demographics and colonoscopic findings were obtained from endoscopy and histology reports. Polyp detection rate, adenoma detection rate, polyps per colonoscopy (PPC) and adenomas per colonoscopy (APC) were calculated. Morning and afternoon lists were combined as both are 4 h long and results were analysed in 20 min segments. Statistical significance was determined by linear regression. <h3>Results</h3> During the 12-month study period, 3923 colonoscopy procedures (60.4±15.3 years, 52.7% female) were performed by 42 endoscopists. 3718 procedures were available for analysis after excluding cases performed in the cross-over period between lists (1300–1400) and out of hours. The average PDR was 35.9% and the ADR 23.9%. Although PDR (p=0.27) and ADR (p=0.24) did not vary significantly during the course of a list, PPC (p=0.015, Abstract OC-048 figure 1) and APC (p=0.025) significantly reduced as lists went on. Results are shown in Abstract OC-048 table 1. <h3>Conclusion</h3> The mean number of polyps and adenomas detected falls significantly during the course of a colonoscopy list. Notably, our data shows no difference in the traditional “detection rate” measures (ADR and PDR) and thus highlights that, in isolation, these may be inadequate measures of colonoscopy quality, and some measure of the number of adenomas detected is also required. The fall in number of adenomas per colonoscopy may relate to operator fatigue and implies that significant lesions could be missed at the end of a list. Further study is required to establish whether revising the length of endoscopy lists or providing a break during a list could prevent this drop off in performance. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Gurudu SR</b>, <i>et al. Am J Gastroenterol</i> 2011;<b>106</b>:1466–71. 2. <b>Lee A</b>, <i>et al. Gastrointest Endosc</i> 2011;<b>73</b>:467–75. 3. <b>Munson GW</b>, <i>et al. Gastrointest Endosc</i> 2011;<b>73</b>:476–9.
Inhibition of Xenografted Human Melanoma Growth and Prevention of Metastasis Development by Dual Antiangiogenic/Antitumor Activities of Pigment Epithelium-Derived Factor
Authors: Marta Garcia, Nuria Isabel Fernandez-Garcia, Veronica Rivas, Marta Carretero, Maria J. Escamez, Alicia Gonzalez-Martin, Estela E. Medrano, Olga Volpert, Jose L. Jorcano, Benilde Jimenez, Fernando Larcher, Marcela Del Rio
Journal: Cancer Research (2004)

Abstract Human melanoma mortality is associated with the growth of metastasis in selected organs including the lungs, liver, and brain. In this study, we examined the consequences of overexpression of pigment epithelium-derived factor (PEDF), a neurotrophic factor and potent angiogenesis inhibitor, on both melanoma primary tumor growth and metastasis development. PEDF overexpression by melanoma cells greatly inhibited subcutaneous tumor formation and completely prevented lung and liver metastasis in immunocompromised mice after tail vein injection of metastatic human melanoma cell lines. Whereas the effects of PEDF on primary tumor xenografts appear mostly associated with inhibition of the angiogenic tumor response, abrogation of melanoma metastasis appears to depend on direct PEDF effects on both migration and survival of melanoma cells. PEDF-mediated inhibition of melanoma metastases could thus have a major impact on existing therapies for melanoma.
Long-term survival after prehospital cardiac arrest: analysis of outcome during an 8 year study.
Authors: R J Myerburg, K M Kessler, D Estes, C A Conde, R M Luceri, L Zaman, P L Kozlovskis, A Castellanos
Journal: Circulation (1984)

We analyzed long-term follow-up data accumulated during an 8 year study of survivors of prehospital cardiac arrest. All patients included in this study were primary entrants via community-based rescue systems; patients who were tertiary referrals (survivors of cardiac arrest from other hospitals) were not included in this analysis. In the group of 61 patients entering our study between 1975 and 1980, with a follow-up to 1983, there have been a total of 24 deaths (39%). Sixteen of the 24 deaths were the result of recurrent cardiac arrest; eight were nonsudden cardiac deaths or noncardiac deaths. The mean duration from entry to death in the nonsurvivors was 27.5 +/- 19.7 months, and the time from the index event to last follow-up in the long-term survivors was 59.9 +/- 19.4 months. Life table analysis demonstrated a 10% rate of recurrence of cardiac arrest in the first year, with a 5% per year rate in each of the subsequent 3 years. Left ventricular ejection fractions at entry were not significantly different between survivors (mean = 45.3 +/- 13.6%) and nonsurvivors (mean = 37.6 +/- 12.6%), and the severity of ejection fraction abnormality at entry did not correlate with time to death in the nonsurvivors. However, ejection fraction was significantly lower in patients who died from causes other than recurrent cardiac arrest than in those who died of cardiac arrest (24.5 +/- 9.1% vs 42.7 +/- 9.2%; p less than .002).(ABSTRACT TRUNCATED AT 250 WORDS)
Comparisons of leisure-time physical activity and cardiorespiratory fitness as predictors of all-cause mortality in men and women
Authors: D-C Lee, X Sui, F B Ortega, Y-S Kim, T S Church, R A Winett, U Ekelund, P T Katzmarzyk, S N Blair
Journal: British Journal of Sports Medicine (2010)

Objective To examine the combined associations and relative contributions of leisure-time physical activity (PA) and cardiorespiratory fitness (CRF) with all-cause mortality. Design Prospective cohort study. Setting Aerobics centre longitudinal study. Participants 31 818 men and 10 555 women who received a medical examination during 1978–2002. Assessment of risk factors Leisure-time PA assessed by self-reported questionnaire; CRF assessed by maximal treadmill test. Main outcome measures All-cause mortality until 31 December 2003. Results There were 1492 (469 per 10 000) and 230 (218 per 10 000) deaths in men and women, respectively. PA and CRF were positively correlated in men (r=0.49) and women (r=0.47) controlling for age (p&lt;0.001 for both). PA was inversely associated with mortality in multivariable Cox regression analysis among men, but the association was eliminated after further adjustment for CRF. No significant association of PA with mortality was observed in women. CRF was inversely associated with mortality in men and women, and the associations remained significant after further adjustment for PA. In the PA and CRF combined analysis, compared with the reference group “not meeting the recommended PA (&lt;500 metabolic equivalent-minute/week) and unfit”, the relative risks (95% CIs) of mortality were 0.62 (0.54 to 0.72) and 0.61 (0.44 to 0.86) in men and women “not meeting the recommended PA and fit”, 0.96 (0.61 to 1.53) and 0.93 (0.33 to 2.58) in men and women “meeting the recommended PA and unfit” and 0.60 (0.51 to 0.70) and 0.56 (0.37 to 0.85) in men and women “meeting the recommended PA and fit”, respectively. Conclusions CRF was more strongly associated with all-cause mortality than PA; therefore, improving CRF should be encouraged in unfit individuals to reduce risk of mortality and considered in the development of future PA guidelines.
A 40-yr-old male with cough, haemoptysis and increasing dyspnoea
Authors: G.C. Riise, M. Bugge, Å.A. Johnsson, H. Willén
Journal: European Respiratory Journal (2001)

Case reportA 40-yr-old Caucasian male was referred to the Dept of Respiratory Diseases because of cough and increasing dyspnoea.He had been through several courses of antibiotics for these symptoms as well as periods of fever during the last 12 months.In spite of this, his nonproductive cough had increased and finally resulted in a haemoptysis 2 weeks prior to the investigation.Weight loss and lack of physical strength were also present at this time.He was a lifelong nonsmoker, lived in the countryside and worked as a carpenter.He had previously been diagnosed with pulmonary sarcoidosis in 1992, and had been treated with tapering doses of peroral corticosteroids and controlled without recurrence of the disease.He is now on no regular medication.Routine physical examination did not show any physical abnormalities.Laboratory investigations revealed blood gas values within the normal range, a slight anaemia (haemoglobin 126 g?L -1 ) and a blood leukocytosis of 14.3610 9 ?L -1 (mainly neutrophils, 87%).Serum level of angiotensin converting enzyme was normal, C-reactive protein was increased to
Polyamines, NO and cGMP mediate stimulation of DNA synthesis by tumor necrosis factor and lipopolysaccharide in chick embryo cardiomyocytes
Authors: B Tantini
Journal: Cardiovascular Research (2001)

We have recently shown that tumor necrosis factor-alpha (TNFalpha) and lipopolysaccharide (LPS) stimulate DNA synthesis in chick embryo cardiomyocytes (CMs). The aim of the present research was to investigate the pathways involved in this mitogenic response.CMs were isolated from 10-day-old chick embryos and grown to confluence. After 20 h of serum starvation the cells were treated with TNFalpha and LPS, and/or specific agonists and antagonists to manipulate the levels of polyamines, NO, cGMP and their biosynthetic enzymes ornithine decarboxylase (ODC), nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC). ODC, NOS, sGC activities and cGMP contents were determined by radiochemical procedures. DNA synthesis was determined by incorporation of [3H]-thymidine.Treatment of CMs with TNFalpha and LPS increased cell number and [3H]-thymidine incorporation. Addition of TNFalpha and LPS provoked an induction of ODC, with consequent polyamine accumulation, and a more delayed enhancement of NOS activity, which appeared to be independent of the activation of the ODC-polyamine system. TNFalpha and LPS treatment also enhanced cGMP level in CMs and both polyamine and NO biosyntheses appeared to be required. Experiments with specific inhibitors of ODC and NOS, as well as with inhibitors of sGC and cGMP-dependent protein kinase (PKG), showed that polyamine-, NO- and cGMP-dependent pathways are required for the mitogenic action of TNFalpha and LPS. Moreover, addition of exogenous polyamines to untreated cells raised the cGMP level in a NO-dependent fashion, and enhanced [3H]-thymidine incorporation. The latter effect was inhibited by sGC or PKG inhibitors. Treatment of quiescent cells with NO donors, 8-bromo-cGMP or YC-1, an sGC activator, also promoted DNA synthesis. Furthermore, putrescine and NO donor can additively activate sGC in cell-free extracts.TNFalpha and LPS stimulate DNA synthesis in chick embryo CMs and this effect is mediated by polyamines, NO and intracellular cGMP.
Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever.
Authors: D Bessen, K F Jones, V A Fischetti
Journal: The Journal of Experimental Medicine (1989)

The antigenic relatedness of surface-exposed portions of M protein molecules derived from group A streptococcal isolates representing more than 50 distinct serotypes was examined. The data indicate that the majority of serotypes fall into two major classes. Class I M protein molecules share a surface-exposed, antigenic domain comprising the C repeat region defined for M6 protein. The C repeat region of M6 protein is located adjacent to the COOH-terminal side of the pepsin-susceptible site. In contrast, Class I M proteins display considerably less antigenic relatedness to the B repeat region of M6 protein, which lies immediately NH2-terminal to the pepsin site. Surface-exposed portions of Class II M proteins lack antigenic epitopes that define the Class I molecules. Studies in the 1970s demonstrated that M protein serotypes can be divided into two groups based on both immunoreactivity directed to an unknown surface antigen (termed M-associated protein) and production of serum opacity factor. These two groups closely parallel our current definition of Class I and Class II serotypes. Both classes retain the antiphagocytic property characteristic of M protein, and Class II M proteins share some immunodeterminants with Class I M proteins, although the shared determinants do not appear to be exposed on the streptococcal surface. Nearly all streptococcal serotypes associated with outbreaks of acute rheumatic fever express M protein of a Class I serotype. Thus, the surface-exposed, conserved C repeat domain of Class I serotypes may be a virulence determinant for rheumatic fever.
Targeted Imaging of Esophageal Neoplasia with a Fluorescently Labeled Peptide: First-in-Human Results
Authors: Matthew B. Sturm, Bishnu P. Joshi, Shaoying Lu, Cyrus Piraka, Supang Khondee, Badih Joseph Elmunzer, Richard S. Kwon, David G. Beer, Henry D. Appelman, Danielle Kim Turgeon, Thomas D. Wang
Journal: Science Translational Medicine (2013)

A fluorescently labeled peptide enables first-in-human targeted endoscopic imaging of esophageal neoplasia.
The Rotavirus Vaccine Saga
Authors: Alan R. Shaw
Journal: Annual Review of Medicine (2005)

Rotavirus is the single most common cause of acute, dehydrating gastroenteritis worldwide. This is a highly contagious and highly democratic disease. The attack rate in infants and young children is similar regardless of sanitation, socioeconomics or geography. Rotavirus vaccine development began in the early 1980s using a "Jennerian" approach based on rotaviruses that normally infect animals. Although these vaccines were found to be generally safe, protection from disease was inconsistent. The second generation of vaccines was based on the same animal viruses configured to carry the relevant coat proteins of human rotaviruses. An attenuated human rotavirus vaccine has also been developed. After close to 20 years of laboratory and clinical studies, safe and effective rotavirus vaccines are approaching regulatory approval.