tbuckley/cabot-search huggingface dataset:
Abstract 5279: Imaging of pancreatic cancer with activated cell penetrating peptide dendrimers
Authors: Cristina A. Metildi, Quyen T. Nguyen, Sharmeela Kaushal, Hop S. Tran Cao, Cynthia S. Snyder, Robert M. Hoffman, Roger Y. Tsien, Michael Bouvet
Journal: Cancer Research (2011)

Abstract We have recently described novel activatable cell penetrating peptides attached to dendrimers (ACPPDs) which can selectively label tumors for real-time imaging during surgery. The aim of this study was to evaluate the ability of Cy5-labeled ACPPDs to visualize primary tumors and their margins in an orthotopic mouse model of pancreatic cancer. BxPC-3 or BxPC-3-RFP-expressing human pancreatic cancer cells were injected into the pancreas of 6-week old athymic mice to establish the orthotopic mouse models. ACPPs were synthesized on an automated peptide synthesizer by using standard protocols for fluorenylmethoxycarbonyl solid-phase synthesis. Peptides were cleaved off the resin, purified by HPLC, and conjugated to a generation 5 PAMAM dendrimer. Cy5 labeling was performed directly on the dendrimer. Dendrimers were then capped completely with Peg4 NHS ester. Tumor-bearing mice were injected with 20 nmoles of ACPPDs via tail vein 48 hours prior to imaging. Mice were first imaged non-invasively using OV-100 (Olympus) or Maestro (CRI) small animal imaging systems. Mice then underwent laparotomy. Resection of the primary pancreatic tumor using fluorescence guidance was performed using a MVX-10 fluorescence-dissecting microscope (Olympus) customized to allow the surgeon to see white-light reflectance, fluorescence, or the two superimposed in real time. At the conclusion of the experiments, H&amp;E staining was used to confirm the pathological diagnosis of cancer in the resected specimens. We found that in the orthotopic BxPC3 mouse model of pancreatic cancer, intravenous injection of ACPPD showed bright fluorescence labeling of tumors compared to surrounding normal tissue. Co-localization studies showed a good correlation between ACPPD uptake and RFP tumor expression. Tumor margins were more clearly delineated with fluorescence imaging using ACPPDs compared to with white light reflectance alone. Post resection, the tumor bed was examined and imaged for residual tumor. With fluorescence-guided resection, the tumor bed was free of residual tumor, which was confirmed histologically. In this study, we have shown that ACPPDs can accurately and effectively label primary pancreatic tumors in an orthotopic mouse model of pancreatic cancer. This technology has the potential to improve surgical outcomes in patients with pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5279. doi:10.1158/1538-7445.AM2011-5279
A Prospective Study of Dietary Fat and Risk of Prostate Cancer
Authors: E. Giovannucci, E. B. Rimm, G. A. Colditz, M. J. Stampfer, A. Ascherio, C. C. Chute, W. C. Willett
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : The strong correlation between national consumption of fat and national rate of mortality from prostate cancer has raised the hypothesis that dietary fat increases the risk of this malignancy. Case-control and cohort studies have not consistently supported this hypothesis. Purpose : We examined prospectively the relationship between prostate cancer and dietary fat, including specific fatty acids and dietary sources of fat. We examined the relationship of fat consumption to the incidence of advanced prostate cancer (stages C, D, or fatal cases) and to the total incidence of prostate cancer. Methods : We used data from the Health Professionals Follow-up Study, which is a prospective cohort of 51529 U.S. men, aged 40 through 75, who completed a validated food-frequency questionnaire in 1986. We sent follow-up questionnaires to the entire cohort in 1988 and 1990 to document new cases of a variety of diseases and to update exposure information. As of January 31, 1990, 300 new cases of prostate cancer, including 126 advanced cases, were documented in 47855 participants initially free of diagnosed cancer. The Mantel-Haenszel summary estimator was used to adjust for age and other potentially confounding variables. Multiple logistic regression was used to estimate relative risks (RRs) when controlling simultaneously for more than two covariates. Results : Total fat consumption was directly related to risk of advanced prostate cancer (age- and energy-adjusted RR = 1.79, with 95% confidence interval [CI] = 1.04–3.07, for high versus low quintile of intake; P [trend] =.06). This association was due primarily to animal fat (RR = 1.63; 95% CI = 0.95–2.78; P [trend] =.08), but not vegetable fat. Red meat represented the food group with the strongest positive association with advanced cancer (RR = 2.64; 95% CI = 1.21–5.77; P =.02). Fat from dairy products (with the exception of butter) or fish was unrelated to risk. Saturated fat, monounsaturated fat, and α-linolenic acid, but not linoleic acid, were associated with advanced prostate cancer risk; only the association with α-linolenic acid persisted when saturated fat, monounsaturated fat, linoleic acid, and α-linolenic acid were modeled simultaneously (multivariate RR = 3.43; 95% CI = 1.67–7.04; P [trend] =.002). Conclusion : The results support the hypothesis that animal fat, especially fat from red meat, is associated with an elevated risk of advanced prostate cancer. Implications : These findings support recommendations to lower intake of meat to reduce the risk of prostate cancer. The potential roles of carcinogens formed in cooking animal fat and of a-linolenic acid in the progression of prostate cancer need to be explored. [J Natl Cancer Inst 85: 1571–1579, 1993]
Laser angioplasty for within stent restenosis — final results of the LARS surveillance study
Authors: C.W. Hamm, R. Simon, R.J.Seabra Gomes, H. Sievert, C. Macaya, E. Fleck, J.J. Bonnier, R. Köster, P.W. Serruys
Journal: Journal of the American College of Cardiology (1998)
Missense Mutations in the Rod Domain of the Lamin A/C Gene as Causes of Dilated Cardiomyopathy and Conduction-System Disease
Authors: Diane Fatkin, Calum MacRae, Takeshi Sasaki, Matthew R. Wolff, Maurizio Porcu, Michael Frenneaux, John Atherton, Humberto J. Vidaillet, Serena Spudich, Umberto De Girolami, J.G. Seidman, Francesco Muntoni, Gerry Müehle, Wendy Johnson, Barbara McDonough, Christine E. Seidman
Journal: New England Journal of Medicine (1999)

Inherited mutations cause approximately 35 percent of cases of dilated cardiomyopathy; however, few genes associated with this disease have been identified. Previously, we located a gene defect that was responsible for autosomal dominant dilated cardiomyopathy and conduction-system disease on chromosome 1p1–q21, where nuclear-envelope proteins lamin A and lamin C are encoded by the LMNA (lamin A/C) gene. Mutations in the head or tail domain of this gene cause Emery–Dreifuss muscular dystrophy, a childhood-onset disease characterized by joint contractures and in some cases by abnormalities of cardiac conduction during adulthood.
The World Stops for the Hungry
Authors: Philip L. White
Journal: JAMA (1971)

The threat of intellectual impairment in malnourished infants has been a political petard breaking down resistance to maternal and child welfare feeding programs. That the case has frequently been overstated in the heat of political debate and rhetoric of presidential messages is forgivable in light of the social progress which has ensued. Until recently, it has been politically fashionable to dogmatically equate malnutrition in childhood with physical and mental retardation. It is true that severe undernutrition during the latter stages of pregnancy and the first few months of life will jeopardize mental and physical development. In an older child, however, nutritional deprivation may create only a maturational lag; ie, with time, the child may overcome the handicap. Malnutrition as a deterrent to social progress should not be taken lightly. Malnutrition can be involved directly or indirectly in the initiation and perpetuation of a disheartened, listless segment of a population, thus
Endurance Training Damages Small Airway Epithelium in Mice
Authors: Laura Chimenti, Giuseppe Morici, Alessandra Paternò, Anna Bonanno, Liboria Siena, Attilio Licciardi, Mario Veca, Walter Guccione, Filippo Macaluso, Giovanni Bonsignore, Maria R. Bonsignore
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

In athletes, airway inflammatory cells were found to be increased in induced sputum or bronchial biopsies. Most data were obtained after exposure to cold and dry air at rest or during exercise. Whether training affects epithelial and inflammatory cells in small airways is unknown.To test whether endurance training under standard environmental conditions causes epithelial damage and inflammation in the small airways of mice.Formalin-fixed, paraffin-embedded lung sections were obtained in sedentary (n = 14) and endurance-trained (n = 16) Swiss mice at baseline and after 15, 30, and 45 days of training. The following variables were assessed (morphometry and immunohistochemistry) in small airways (basement membrane length < 1 mm): (1) integrity, proliferation, and apoptosis of bronchiolar epithelium; and (2) infiltration, activation, and apoptosis of inflammatory cells.Compared with sedentary mice, bronchiolar epithelium of trained mice showed progressive loss of ciliated cells, slightly increased thickness, unchanged goblet cell number and appearance, and increased apoptosis and proliferation (proliferating cell nuclear antigen) (p < 0.001 for all variables). Leukocytes (CD45(+) cells) infiltrated airway walls (p < 0.0001) and accumulated within the lumen (p < 0.001); however, apoptosis of CD45(+) cells did not differ between trained and sedentary mice. Nuclear factor-kappaB translocation and inhibitor-alpha of NF-kappaB (IkappaBalpha) phosphorylation were not increased in trained compared with sedentary mice.Bronchiolar epithelium showed damage and repair associated with endurance training. Training increased inflammatory cells in small airways, but inflammatory activation was not increased. These changes may represent an adaptive response to increased ventilation during exercise.
596. Incorporation of a Hepatocyte-Specific Compound in Polycationic Liposomes Enhances Gene Transfection in Hep G2 Cells
Authors: Michelle R. McCombs, Gideon O. Berger, Michael H. Nantz, Jian Wu
Journal: Molecular Therapy (2005)

Background: Cationic liposomes generated from poly(cationic lipid) (PCL) and cholesterol (Chol) have been demonstrated to be a very effective formulation for in vivo gene delivery (Liu et al. Gene Therapy 2003; 10: 180-187), and our polycationic liposome-mediated extracellular superoxide dismutase gene delivery prevented hepatotoxin-induced acute liver injury in mice (Wu et al. Hepatology 2004; 40: 195-204). To enhance targeted gene delivery of cationic liposomes to the liver, particularly to hepatocytes, on which exist abundant asialoglycoprotein receptors (ASGP-R) that mediate ligand-specific endocytosis, we conjugated galactose to a derivative of dimyristylbutanediketone (DMBDK). The resulting new galactose-labeled compound is termed as Gal-S12-DMBDOE.
Abstract 4246: Granulin-epithelin precursor (GEP) is an oncofetal protein involved in fetal liver development and liver cancer
Authors: Phyllis Fung Yi Cheung, Siu Tim Cheung
Journal: Cancer Research (2010)

Abstract Background and objectives: Granulin-epithelin precursor (GEP) is a novel pluripotent growth factor regulating embryo development, wound repair and tumorigenesis. Our group previously has showed that GEP was over-expressed in over 70% of liver cancer. Besides, functional studies demonstrated that GEP controlled liver cancer proliferation, invasion and tumorigenicity. In this study, we aim to examine the time-frame of GEP expression during fetal liver development, and to characterize the properties of GEP-expressing liver cells. Methods: GEP expression was examined by immunofluorescence using flow cytometry and immunohistochemistry. The properties of GEP-expressing cells were characterized by measuring the co-expression of GEP and various stem/progenitor cell markers using immunofluorescence and flow cytometry. Correlation of GEP level with the expression of stem/progenitor markers was studied by transfection experiments. Results: In murine model, GEP expression was observed to increase gradually from embryonic day (E) 11 to E17, with up to 49% fetal liver cells were GEP positive. Immediately after birth, GEP expression decreased abruptly from day 1, and by day 7, less than 1% neonatal liver cells were GEP positive, and GEP was not detectable in adult liver. In human, fetal liver at 10 weeks old were demonstrated to express GEP protein, while normal adult livers were devoid of GEP-expressing cells. GEP expression was up-regulated in liver cancer cells compared with the adjacent non-tumor liver cells. Moreover, we showed that GEP co-expressed with hematopoietic stem/progenitor cell marker CD34, liver cancer stem cell marker CD326, and stem cell-related signaling molecules β-catenin and Oct4, suggesting a stem/progenitor cell feature of the GEP-expressing cells. Furthermore, up-regulation of GEP level enhanced the expression of β-catenin and Oct4, and suppression of GEP level resulted in decreased expression of these molecules. Conclusion: The present data suggests that GEP is an oncofetal protein, and GEP regulates the expression of stem cell-related signaling molecules. This information advances our knowledge on the fundamental role of GEP in fetal liver development and liver carcinogenesis, and provides valuable insights on the use of GEP as a therapeutic target in the treatment of liver cancer. Category: Tumor Biology Sub-classification: TB2: stem cell biology/cancer stem cells/developmental oncobiology Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4246.
Modulation of bronchial epithelial cells by IL-17
Authors: Mio Kawaguchi, Fumio Kokubu, Hideki Kuga, Satoshi Matsukura, Hiroshi Hoshino, Koushi Ieki, Toshimichi Imai, Mitsuru Adachi, Shau-Ku Huang
Journal: Journal of Allergy and Clinical Immunology (2001)
Effect of physiological mechanical perturbations on intact human myocardial repolarization
Authors: K Nanthakumar
Journal: Cardiovascular Research (2000)

The objective of this study was to investigate the relationship between acute decreases in right ventricular volume during Valsalva strain (with resultant changes in autonomic neural tone) and measures of local endocardial repolarization time independent of heart rate and autonomic neural tone.Patients implanted with a stimulus to T wave (Stim-T) sensing pacemaker specially adapted to output a validate measure of beat to beat local repolarization (n = 9) performed Valsalva manoeuvers (40 mmHg for 15 s) while paced at a cycle length of 500 ms. Stim-T intervals were measured before and after autonomic blockade (Block: 0.03 mg/kg i.v. atropine +/- 0.15 mg/kg propranolol). Right ventricular end diastolic volume was estimated by simultaneous 2D-echocardiography.Without autonomic blockade, compared to baseline, repolarization significantly prolonged during Valsalva strain (1.1 +/- 0.7%) and shortened during release (-1.4 +/- 1.0%). After block, strain related repolarization prolongation was also observed (1.0 +/- 0.6%), with significantly less release related repolarization shortening (-0.8 +/- 0.8%) compared to pre-block (P < 0.05). Right ventricular end diastolic volume decreased during strain by 11 +/- 10 and 9 +/- 16% from baseline, pre- and post-block respectively (P < 0.05).In a chronically instrumented human model, an acute physiologic volume reduction modestly prolongs right ventricular repolarization independent of changes in rate or autonomic tone.
Enterohemorrhagic and enteropathogenic Escherichia coli evolved different strategies to resist antimicrobial peptides
Authors: Jenny-Lee Thomassin, John R. Brannon, Julienne Kaiser, Samantha Gruenheid, Hervé Le Moual
Journal: Gut Microbes (2012)

Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are enteric human pathogens that colonize the large and small intestines, respectively. To establish infection EHEC and EPEC must overcome innate host defenses, such as antimicrobial peptides (AMPs) produced by the intestinal epithelium. Gram-negative pathogens have evolved different mechanisms to resist AMPs, including outer-membrane proteases that degrade AMPs. We showed that the protease OmpT degrades the human AMP LL-37 more rapidly in EHEC than in EPEC. Promoter-swap experiments showed that this is due to differences in the promoters of the two genes, leading to greater ompT expression and subsequently greater levels of OmpT in EHEC. Here, we propose that the different ompT expression in EHEC and EPEC reflects the varying levels of LL-37 throughout the human intestinal tract. These data suggest that EHEC and EPEC adapted to their specific niches by developing distinct AMP-specific resistance mechanisms.
Enzymes in normally perfused and ischaemic dog hearts which release a substance with kinin like activity
Authors: I J ZEITLIN, S O FAGBEMI, J R PARRATT
Journal: Cardiovascular Research (1989)

Journal Article Enzymes in normally perfused and ischaemic dog hearts which release a substance with kinin like activity Get access I J ZEITLIN, I J ZEITLIN Address for correspondence and reprints: Dr I J Zeitlin, Department of Physiology & Pharmacology, University of Strathclyde, George Street, Glasgow G1 1XW, Scotland, UK. Search for other works by this author on: Oxford Academic PubMed Google Scholar S O FAGBEMI, S O FAGBEMI 1Present Address: Department of Pharmacology & Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria Search for other works by this author on: Oxford Academic PubMed Google Scholar J R PARRATT J R PARRATT Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 23, Issue 2, February 1989, Pages 91–97, https://doi.org/10.1093/cvr/23.2.91 Published: 01 February 1989 Article history Accepted: 09 September 1988 Published: 01 February 1989
Tobacco Dependence Curricula in US Undergraduate Medical Education
Authors: Linda Hyder Ferry
Journal: JAMA (1999)

Tobacco use is the leading preventable cause of death in the United States. And yet only 21% of practicing physicians claim they received adequate training to help their patients stop smoking.To assess the content and extent of tobacco education and intervention skills in US medical schools' curricula.A survey with 13 multiple-response items on tobacco education. Survey questions were based on the recommendations of the Agency for Health Care Policy and Research and the National Cancer Institute Expert Panel. The Liaison Committee on Medical Education included 4 of these items in a modified form on the 1997 annual questionnaire.One hundred twenty-six US medical schools.Surveys were obtained from 122 associate deans for medical education (98.6%).Curriculum content in basic science and clinical science, elective or required clinical experience, hours of instruction, and resource materials.Inclusion of all 6 tobacco curricula content areas recommended by the National Cancer Institute and the Agency for Health Care Policy and Research was higher in basic science (63/115 [54.8%]) than in clinical science (5/115 [4.4%]). Most medical schools (83/120 [69.2%]) did not require clinical training in smoking cessation techniques, while 23.5% (27/115) offered additional experience as an elective course. Thirty-one percent (32/102) of schools averaged less than 1 hour of instruction per year in smoking cessation techniques during the 4 years of medical school. A minority of schools reported 3 or more hours of clinical smoking cessation instruction in the third (14.7%) and fourth (4.9%) years.A majority of US medical school graduates are not adequately trained to treat nicotine dependence. The major deficit is the lack of smoking cessation instruction and evaluation in the clinical years. A model core tobacco curricula that meets national recommendations should be developed and implemented in all US medical schools.
Expression of intercellular adhesion molecule-1 on rat cardiac myocytes by monocyte chemoattractant protein-1
Authors: K. Ban, U. Ikeda, M. Takahashi, T. Kanbe, T. Kasahara, K. Shimada
Journal: Cardiovascular Research (1994)

Objective: Cytokine induction of intercellular adhesion molecule-1 (ICAM-1) on cardiac myocytes may be a critical step in cardiac inflammation associated with acute myocardial infarction and myocarditis. The aim of this study was to investigate the involvement of monocyte chemoattractant protein-1 (MCP-1), a homologue of mouse JE, in the neutrophil-myocyte adhesion in vitro. Methods: MCP-1/JE and ICAM-1 mRNA expression in cultured neonatal rat cardiac myocytes was evaluated by northern blot analysis. ICAM-1 molecule content on myocytes was determined by ELISA. For adherence assay, myocytes and neutrophils were co-incubated and the number of bounded neutrophils was counted. Results: MCP-l/JE transcripts were not clearly observed in cultured neonatal rat cardiac myocytes; however, its transcripts were clearly detected by exposure to interleukin lα (100 U·ml−1), lipopolysaccharide (1 μg·ml−1), or hypoxia (95% N2 + 5% CO2). In ELISA analysis, the expression of ICAM-1 molecules on cardiac myocytes was significantly stimulated by MCP-1 in a dose dependent manner, and the effect of MCP-1 was observed as early as at 6 h. In northern blot analysis, ICAM-1 mRNA expression was constitutively observed in myocytes, and the expression was markedly stimulated by exposure to MCP-1 with a peak elevation at 2 h. In adherence assay, MCP-1 stimulated the adhesion of rat neutrophils to rat cardiac myocytes, and this effect of MCP-1 was inhibited by an anti-ICAM-I MAb. Conclusions: These results suggest that cardiac myocytes produce MCP-1, which could in turn promote the adhesion of neutrophils to myocytes via ICAM-1 expression, suggesting the involvement of MCP-1 in cardiac inflammation associated with acute myocardial infarction and myocarditis. Cardiovascular Research 1994;28:1258-1262
Ice in the treatment of sports injuries
Authors: Yvonne Wootton-Whitling
Journal: British Journal of Sports Medicine (1977)

We have heard from Dr. Ian Adams of the problems of treating the injured athlete through the over worked and creaking National Health Service Casualty Departments. I believe that of the nine experimental sports injuries clinics set up some time ago four survive, the other five, victims of manpower and financial shortages. It is because of this and the unsatisfactory service that the injured sportsmen frequently receives through the N.H.S. that the private practitioner finds that there is a part to play.