tbuckley/cabot-search huggingface dataset:
Telomere Attrition in Cancer Cells and Telomere Length in Tumor Stroma Cells Predict Chromosome Instability in Esophageal Squamous Cell Carcinoma: A Genome-Wide Analysis
Authors: Yun-Ling Zheng, Nan Hu, Qing Sun, Chaoyu Wang, Philip R. Taylor
Journal: Cancer Research (2009)

Previous studies showed that chromosomal instability was common in esophageal squamous cell carcinoma (ESCC); however, the mechanisms underlying this instability are unknown. Individuals with deficiencies in telomere maintenance are susceptible to enhanced telomere loss during cell proliferation; such deficiencies could result in telomere dysfunction and genomic instability. We investigated the association between genome-wide chromosomal changes in cancer cells and telomere length/attrition in cancer/stroma cells in 47 ESCC patients. Genome-wide detection of loss of heterozygosity was performed using the Affymetrix GeneChip single nucleotide polymorphism arrays. Telomere length was assessed separately for cancer cells, carcinoma-associated fibroblasts (CAF), infiltrative lymphocytes, and adjacent normal epithelial cells by quantitative fluorescent in situ hybridization using paraffin-embedded sections. Telomere length differed significantly among cell types, such that length in infiltrative lymphocytes > CAFs > cancer cells. Shortened telomeres were observed in cancer cells in 44 of 47 (94%) of the tumors examined. Telomere length in CAFs was significantly associated with chromosomal instability on 4q and 13q and lymphocyte telomere length was significantly associated with instability on chromosomal arms 15q. Although telomere length in cancer cells was not associated with chromosome arm instability, telomere attrition in cancer cells, defined as the telomere length in CAFs minus the telomere length in cancer cells, was significantly associated with chromosomal instability on 13q and 15q. This study provides evidence that telomere shortening is a common genetic alteration in ESCC and that chromosome arm instability is related to both telomere attrition in cancer cells and telomere length in tumor stroma cells.
Reporter Gene Imaging of Immune Responses to Cancer: Progress and Challenges
Authors: Purnima Dubey
Journal: Theranostics (2012)

Immune responses to cancer are dynamic processes which take place through the concerted activity of innate and adaptive cell populations. In order to fully understand the efficacy of immune therapies for cancer, it is critical to understand how the treatment modulates the function of each cell type involved in the anti-tumor immune response. Molecular imaging is a versatile method for longitudinal studies of cellular localization and function. The development of reporter genes for tracking cell movement and function was a powerful addition to the immunologist's toolbox. This review will highlight the advances and challenges in the use of reporter gene imaging to track immune cell localization and function in cancer.
Cytotoxic T lymphocytes induced against allogeneic I-region determinants react with Ia molecules on trinitrophenyl-conjugated syngeneic target cells
Authors: P Billings, S Burakoff, ME Dorf, B Benacerraf
Journal: The Journal of Experimental Medicine (1977)

The major histocompatibility complex codes for determinants which are recognized by and serve as targets for cytolytic T lymphocytes (CTL) (1). Antigens coded for by the K and D loci of the H-2 complex can activate xenogeneic or allogeneic CTL (2,3). In addition, the H-2K or H-2D gene products function as those molecules against which syngeneic CTL responses specific for chemical, viral, and minor H antigens are directed (4-8). It has recently been shown that Ia determinants can also serve as target antigens for distinct but weaker CTL responses (9-13). Those clones which recognize Ia antigens see them independently of K- or D- coded antigens as shown in genetic studies and by antisera-blocking experiments (12,13). We have proposed that the existence of clones of CTL specific for I-region-coded determinants is not fortuitous; rather these clones specifically recognize Ia determinants and may have an immunoregulatory role. These CTL may affect those immune functions which are at least partially dependent on or controlled by I-region-coded molecules. Two predictions can be made and tested concerning the role of Ia determinants in cytolytic systems and the role, if any, of I-region- specific CTL in regulating the immune response: (a) that if as we and others have shown, certain Ia specificities can serve as a third series of major histocompatibility antigens, then Ia antigens should be susceptible to the same types of antigenic modifications as H-2K- or H-2D-coded structures and thus serve as targets for CTL directed against modified-self in selected systems; and (b) that allogeneically induced I-region-specific CTL should demonstrate cross-reactivity with targets bearing modified syngeneic I-region-coded determinants. Data will be present which demonstrates that trinitrophenyl (TNP)-modified syngeneic I-region determinants can serve as targets for CTL induced by allogeneic Ia antigens.
Combined Effect of Nonalcoholic Fatty Liver Disease and Impaired Fasting Glucose on the Development of Type 2 Diabetes
Authors: Ji Cheol Bae, Eun Jung Rhee, Won Young Lee, Se Eun Park, Cheol Young Park, Ki Won Oh, Sung Woo Park, Sun Woo Kim
Journal: Diabetes Care (2011)

To evaluate whether there is a difference in the association between nonalcoholic fatty liver disease (NAFLD) and incident diabetes based on the presence of impaired fasting glucose.A total of 7,849 individuals (5,409 men and 2,440 women) without diabetes, who underwent comprehensive health check-ups annually for 5 years, were categorized into four groups by the presence of impaired fasting glucose and NAFLD at baseline. The association between NAFLD and incident diabetes was evaluated separately in groups with normal and impaired fasting glucose.For 4 years, the incidence of diabetes in the NAFLD group was 9.9% compared with 3.7% in the non-NAFLD group, with multivariable-adjusted hazard ratio of 1.33 (95% CI 1.07-1.66). However, this higher risk for diabetes only existed in the impaired fasting glucose group.Our study suggests that NAFLD has an independent and additive effect on the development of diabetes under conditions of impaired insulin secretion.
Abstract 2515: Tumor presenting cells: a new strategy for cancer immunotherapy
Authors: Fernando T. Kreutz
Journal: Cancer Research (2015)

Abstract Solid tumor cells as other non-immunological cells do not present MHC Class II. The MHC class II is a critical molecule responsible for peptide presentation to T helper cells. The presence of a not-self peptide on a MHC II molecule trigger the production of cytokines responsible for different steps on T cell expansion and maturation. Without the appropriate cytokine stimulation, cytotoxic T cells that identified a not-self peptide associate to a MHC class I molecules, may not proliferate or even be induce to anergy. We hypothesized that lack of anti-tumor immune responses on the majority of cancer patients (too little, too late) is due to a not appropriate MHC II peptide presentation. In our model, solid tumor cells (prostate cancer) are induce to express MHCII on their surface. In this novel approach of Cell Based Cancer Immunotherapy, patient's tumor cells were expanded in tissue culture and treated causing de novo expression of MHC II and activation of the MHC II peptide presentation pathway. Thus, the modified cancer cells are bifunctional, being capable of activating both helper T cells (MHC II) and cytotoxic T cells (MHCI), leading to cytokine production and a surprisingly robust and cancer-specific immune response. The modified solid tumor cell by itself will now behave as an antigen-presenting cell creating a Tumor Presenting Cell (TPC). As previous reported on a Phase IIb clinical trial done in Brazil (FK-Biotec/UFRGS/PUCRS), a population of local advance prostate cancer patients were treated with TPC. The study showed a significant (p = 0,03) increase in number of patients with undetectable levels of PSA (biochemical cure) after 5 years, 85% versus 48% on the control group. Also shown a trend of lowering mortality by prostate cancer, 9% in the threated group versus 19% in the control group. In conclusion, we are describing a novel Cell Based Cancer Immunotherapy that could be apply to several different tumor types. Citation Format: Fernando T. Kreutz. Tumor presenting cells: a new strategy for cancer immunotherapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2515. doi:10.1158/1538-7445.AM2015-2515
Endothelial Nuclear Factor κB in Obesity and Aging
Authors: Jason K. Kim
Journal: Circulation (2012)

I nsulin resistance is a major characteristic of type 2 diabetes mellitus and develops in multiple organs, including skeletal muscle, liver, adipose tissue, and heart. 1 Insulin resistance is caused by obesity and therefore establishes an important causal relationship between obesity and type 2 diabetes mellitus. 2Insulin resistance also develops in aging, but this process is less well understood.Obesity is a complex physiological state, with alterations in lipid metabolism, dysregulated production of hormones, ectopic accumulation of fat, mitochondrial dysfunction, and chronic low-grade inflammation. 3,4All of these abnormalities may independently cause insulin resistance and affect glucose homeostasis, which make insulin resistance equally as complex as obesity itself.
Acute Pulmonary Oedema
Authors: A. H. Morley
Journal: BMJ (1957)

<h3>Abstract</h3> Bacteriophage, viruses that infect bacteria, are abundant in the human body but the relationship between the phageome and bacterial population dynamics is unclear. Because bacteriophage are often highly specific to bacterial host strains and species, we asked whether bacteriophage present in cell-free DNA (cfDNA) reflect bacterial infections in sepsis and other infections. To address this, we generate a computational pipeline for identifying bacteriophage sequences in cfDNA. In three large, independent cohorts of infected patients and asymptomatic controls, we demonstrate that all individuals have a circulating phageome. Moreover, infection associates with overrepresentation of pathogen-specific phage, allowing for identification of bacterial pathogens. We further show that phage can identify pathovariant Escherichia coli infections and distinguish between closely-related pathogenic bacteria such as Staphylococcus aureus and frequent contaminants such as coagulase-negative Staphylococcus. Phage DNA may have utility in identifying bacterial pathogens in infection and studying bacterial dynamics.
Elemental diets in treatment of acute Crohn's disease.
Authors: C O'Morain, A W Segal, A J Levi
Journal: BMJ (1980)

Twenty-seven patients with 32 acute exacerbations of Crohn's disease were treated for four weeks with an elemental diet. At the end of treatment 29 of the exacerbations had remitted both clinically and biochemically. After six months six patients had relapsed. These findings suggest that the elemental diet is effective in treating acute Crohn's disease, but the reasons are not clear. The diet may be effective because it provides nutritional support, is hypoallergenic, acts as a medical bypass from the affected area, or alters bowel flora. The patient's general wellbeing is improved by the supply of adequate energy and essential foodstuffs in a form easily available without further digestion and given in a safe, simple, non-toxic way.
Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism
Authors: Non Renseigné, Harry R Büller, Martin H Prins, Anthonie W A Lensin, Hervé Decousus, Barry F Jacobson, Erich Minar, Jaromir Chlumsky, Peter Verhamme, Phil Wells, Giancarlo Agnelli, Alexander Cohen, Scott D Berkowitz, Henri Bounameaux, Bruce L Davidson, Frank Misselwitz, Alex S Gallus, Gary E Raskob, Sebastian Schellong, Annelise Segers, Dominique Mottier
Journal: New England Journal of Medicine (2012)

A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism.
Active loading liposomal irinotecan hydrochloride: Preparation, in vitro and in vivo evaluation
Authors: Hongyan Wei, Juan Song, Hao Li, Yang Li, Shanshan Zhu, Xiaodan Zhou, Xiwen Zhang, Li Yang
Journal: Asian Journal of Pharmaceutical Sciences (2013)

The aim of the present study was to investigate the effect of various transmembrane ammonium salt gradients and different lipid composition on the loading efficiency of liposomal formulations of irinotecan hydrochloride (CPT-11), their behavior in vivo and cytotoxicity. Among ammonium salts studied, ammonium sulfate was successfully used to load CPT-11 into liposomes with the highest encapsulation efficiency. Subsequently, liposomal CPT-11 with different lipid composition was prepared by ammonium sulfate gradient method. CPT-11 can be loaded to a level over 90% into liposomes composed of soybean phospholipids/cholesterol (SPC-L) or hydrogenated natural soybean phospholipids/cholesterol (HSPC-L). In vitro release profiles were also investigated, indicating that HSPC-L had a lower release than that in SPC-L. In vivo, encapsulation of CPT-11 in both liposomal formulations showed higher area under the curve (AUC), a lower rate of clearance (CL) and smaller volume of distribution for CPT-11 than those of irinotecan hydrochloride solution (CPT-11-S). However, CL and AUC of 7-ethyl-10-hydroxycamptothecin (SN-38) were moderately improved in HSPC-L group. Based on the results of comparative pharmacokinetics of liposomal CPT-11 with different lipid composition, the in vitro cytotoxicity of HSPC-L was evaluated with human tumor cell. The result indicated that liposomal CPT-11 showed a great enhancement in vitro cytotoxicity. The results suggested that entrapment of CPT-11 in liposomes especially in those with high phase-transition temperature lipid by ammonium sulfate gradient would be a promising formulation with a better in vivo behavior.
Influence of a prostaglandin endoperoxide analogue on the canine pulmonary vascular bed.
Authors: P J Kadowitz, A L Hyman
Journal: Circulation Research (1977)

We evaluated the effects of an analogue of the prostaglandin endoperoxide, PGH2, in the canine pulmonary vascular bed. The analogue increased pulmonary arterial pressure whereas cardiac output and left atrial pressure were unchanged. Although pulmonary vascular resistance was increased markedly, only small increases in systemic vascular resistance were observed. In experiments in which blood flow to a lobe was maintained constant, the analogue produced dose-related increases in lobar arterial and small vein pressure but little change in left atrial pressure. These data suggest that the analogue increased resistance to flow by constricting intrapulmonary veins and upstream vessels presumed to be small arteries. The increase in resistance was similar when the lung was perfused with dextran or with blood. In addition, the analogue increased inflation pressure; however, similar increments in vascular resistance were obtained in ventilated and nonventilated lung lobes. Indomethacin, in doses which abolished responses to arachidonic acid, did not attenuate the response to the analogue. These results suggest that interaction with formed elements, increases in airway tone, or stimulation of prostaglandin synthesis contribute little if anything to the pressor response to the analogue. These data show that the analogue is far more potent than the bisenoic prostaglandins in the pulmonary vascular bed and suggest that endoperoxides may represent an active form of the prostaglandins in the lung.
Effect of fatty acids on glucose production and utilization in man.
Authors: E Ferrannini, E J Barrett, S Bevilacqua, R A DeFronzo
Journal: Journal of Clinical Investigation (1983)

Since the initial proposal of the glucose fatty acid cycle, considerable controversy has arisen concerning its physiologic significance in vivo. In the present study, we examined the effect of acute, physiologic elevations of FFA concentrations on glucose production and uptake in normal subjects under three controlled experimental conditions. In group A, plasma insulin levels were raised and maintained at approximately 100 microU/ml above base line by an insulin infusion, while holding plasma glucose at the fasting level by a variable glucose infusion. In group B, plasma glucose concentration was raised by 125 mg/100 ml and plasma insulin was clamped at approximately 50 microU/ml by a combined infusion of somatostatin and insulin. In group C, plasma glucose was raised by 200 mg/100 ml above the fasting level, while insulin secretion was inhibited with somatostatin and peripheral glucagon levels were replaced with a glucagon infusion (1 ng/min X kg). Each protocol was repeated in the same subject in combination with a lipid-heparin infusion designed to raise plasma FFA levels by 1.5-2.0 mumol/ml. With euglycemic hyperinsulinemia (study A), lipid infusion caused a significant inhibition of total glucose uptake (6.3 +/- 1.3 vs. 7.4 +/- 0.6 mg/min X kg, P less than 0.02). Endogenous glucose production (estimated by the [3-3H]glucose technique) was completely suppressed both with and without lipid infusion. With hyperglycemic hyperinsulinemia (study B), lipid infusion also induced a marked impairment in glucose utilization (6.2 +/- 1.1 vs. 9.8 +/- 1.9 mg/min X kg, P less than 0.05); endogenous glucose production was again completely inhibited despite the increase in FFA concentrations. Under both conditions (A and B), the percentage inhibition of glucose uptake by FFA was positively correlated with the total rate of glucose uptake (r = 0.69, P less than 0.01). In contrast, when hyperglycemia was associated with relative insulinopenia and hyperglucagonemia (study C), thus simulating a diabetic state, lipid infusion had no effect on glucose uptake (2.9 +/- 0.2 vs. 2.6 +/- 0.2 mg/min X kg) but markedly stimulated endogenous glucose production (1.4 +/- 0.5 vs. 0.5 +/- 0.4 mg/min X kg, P less than 0.005). Under the same conditions as study C, a glycerol infusion producing plasma glycerol levels similar to those achieved with lipid-heparin, enhanced endogenous glucose production (1.5 +/- 0.5 vs. 0.7 +/- 0.6 mg/min X kg, P less than 0.05). We conclude that, in the well-insulinized state raised FFA levels effectively compete with glucose for uptake by peripheral tissues, regardless of the presence of hyperglycemia. When insulin is deficient, on the other hand, elevated rates of lipolysis may contribute to hyperglycemia not by competition for fuel utilization, but through an enhancement of endogenous glucose output.
Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: systematic review and meta-analysis
Authors: M. Schweizer, E. Perencevich, J. McDanel, J. Carson, M. Formanek, J. Hafner, B. Braun, L. Herwaldt
Journal: BMJ (2013)

<b>Objective</b> To evaluate studies assessing the effectiveness of a bundle of nasal decolonization and glycopeptide prophylaxis for preventing surgical site infections caused by Gram positive bacteria among patients undergoing cardiac operations or total joint replacement procedures. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> PubMed (1995 to 2011), the Cochrane database of systematic reviews, CINAHL, Embase, and clinicaltrials.gov were searched to identify relevant studies. Pertinent journals and conference abstracts were hand searched. Study authors were contacted if more data were needed. <b>Eligibility criteria</b> Randomized controlled trials, quasi-experimental studies, and cohort studies that assessed nasal decolonization or glycopeptide prophylaxis, or both, for preventing Gram positive surgical site infections compared with standard care. <b>Participants</b> Patients undergoing cardiac operations or total joint replacement procedures. <b>Data extraction and study appraisal</b> Two authors independently extracted data from each paper and a random effects model was used to obtain summary estimates. Risk of bias was assessed using the Downs and Black or the Cochrane scales. Heterogeneity was assessed using the Cochran Q and I<sup>2</sup> statistics. <b>Results</b> 39 studies were included. Pooled effects of 17 studies showed that nasal decolonization had a significantly protective effect against surgical site infections associated with <i>Staphylococcus aureus</i> (pooled relative risk 0.39, 95% confidence interval 0.31 to 0.50) when all patients underwent decolonization (0.40, 0.29 to 0.55) and when only <i>S aureus</i> carriers underwent decolonization (0.36, 0.22 to 0.57). Pooled effects of 15 prophylaxis studies showed that glycopeptide prophylaxis was significantly protective against surgical site infections related to methicillin (meticillin) resistant <i>S aureus</i> (MRSA) compared with prophylaxis using β lactam antibiotics (0.40, 0.20 to 0.80), and a non-significant risk factor for methicillin susceptible <i>S aureus</i> infections (1.47, 0.91 to 2.38). Seven studies assessed a bundle including decolonization and glycopeptide prophylaxis for only patients colonized with MRSA and found a significantly protective effect against surgical site infections with Gram positive bacteria (0.41, 0.30 to 0.56). <b>Conclusions</b> Surgical programs that implement a bundled intervention including both nasal decolonization and glycopeptide prophylaxis for MRSA carriers may decrease rates of surgical site infections caused by <i>S aureus</i> or other Gram positive bacteria.
Control of Coronary Blood Flow by an Autoregulatory Mechanism
Authors: PAUL MOSHER, JOHN ROSS, PATRICIA ANN MCFATE, ROBERT F. SHAW
Journal: Circulation Research (1964)

Control of the coronary circulation has been investigated in an experimental preparation in which coronary flow was suddenly increased or decreased by the imposition of sudden changes in coronary perfusion pressure during periods of constant cardiac performance. The transient response to these changes in coronary perfusion pressure was an initial abrupt change in flow in the same direction, followed by a prompt return of flow toward the previous level. The response was completed in 10 to 15 sec, and was followed by a few cycles of damped oscillation having a period of 10 to 12 sec. Steady-state pressure-flow curves demonstrated a range of perfusion pressures over which coronary blood flow was relatively independent of pressure. Below this pressure range the coronary bed appeared to be fully dilated, and the blood flow was directly dependent upon perfusion pressure. Elevation of the level of cardiac function resulted in autoregulation of coronary flow at a higher level of flow, and decreasing the level of cardiac function resulted in regulation of coronary flow at a lower flow rate. Instantaneous pressure-flow characteristics of the coronary bed, exclusive of compensatory influences, were also determined. The experiments demonstrated an intrinsic mechanism that regulated blood flow to the myocardium. In the physiologic range of arterial pressure, coronary perfusion pressure did not appear to be a major determinant of coronary blood flow. Coronary flow appeared to be autoregulated at a level related to myocardial effort.