tbuckley/cabot-search huggingface dataset:
The Effect of Iron and Erythropoietin Treatment on the A1C of Patients With Diabetes and Chronic Kidney Disease
Authors: Jen M. Ng, Michelle Cooke, Sunil Bhandari, Stephen L. Atkin, Eric S. Kilpatrick
Journal: Diabetes Care (2010)

OBJECTIVE To examine the effect of intravenous iron and erythropoietin-stimulating agents (ESAs) on glycemic control and A1C of patients with diabetes and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS This was a prospective study of patients with type 2 diabetes and CKD stage IIIB or IV undergoing intravenous iron (group A) and/or ESA (group B). Full blood profiles were determined over the study period. Glycemic control was monitored using A1C, seven-point daily glucose three times weekly, and continuous glucose monitoring (CGM). RESULTS There were 15 patients in both group A and group B. Mean A1C (95% CI) values fell in both groups (7.40% [6.60–8.19] to 6.96% [6.27–7.25], P &amp;lt; 0.01, with intravenous iron and 7.31% [6.42–8.54] to 6.63% [6.03–7.36], P = 0.013, ESA). There was no change in mean blood glucose in group A (9.55 mmol/l [8.20–10.90] vs. 9.71 mmol/l [8.29–11.13], P = 0.07) and in group B (8.72 mmol/l [7.31–10.12] vs. 8.78 mmol/l [7.47–9.99], P = 0.61) over the study period. Hemoglobin and hematocrit values significantly increased following both treatments. There was no linear relationship found between the change in A1C values and the rise of hemoglobin following either treatment. CONCLUSIONS Both iron and ESA cause a significant fall in A1C values without a change to glycemic control in patients with diabetes and CKD. At the present time, regular capillary glucose measurements and the concurrent use of CGM remain the best alternative measurements of glycemic control in this patient group.
Relationship between expression of herpes simplex virus glycoproteins and susceptibility of target cells to human natural killer activity.
Authors: G A Bishop, J C Glorioso, S A Schwartz
Journal: The Journal of Experimental Medicine (1983)

Cells normally insensitive to human natural killer (NK) activity were rendered susceptible by infection with HSV-1. The cytotoxic effector cell was a nonadherent, non-T, non-B lymphocyte. Antibody plus complement treatment, using a monoclonal antibody that recognizes an antigen present on NK cells, removed much of the cytotoxic activity, and a density gradient fraction enriched for NK cells yielded cells of increased virus-specific cytotoxicity. It was concluded that the effector cell active against infected targets possessed characteristics of an NK cell. Blockage of viral protein synthesis during infection inhibited development of increased susceptibility of infected targets to NK activity. When targets were infected with a mutant virus unable to produce viral glycoprotein C (gC), NK activity against these targets was reduced approximately 30% compared with activity against targets infected with wild-type virus. Similarly, activity against targets infected in the presence of 2-deoxyglucose (2dG), which prevents cell surface expression of viral glycoprotein B (gB), was also reduced approximately 30%. An approximately 60% reduction in activity was seen against targets infected with mutant virus in the presence of 2dG; these targets express gD, but neither gB nor gC. When cells expressing various combinations of HSV-1 glycoproteins were used as both labeled targets and cold target competitors, it was found that the susceptibility of a particular target to NK activity was paralleled by its ability to act as a cold target competitor. This indicates that targets with decreased sensitivity to NK cells were less able to bind NK effectors. Further, the amount of interferon produced in co-cultures of NK effectors and infected target cells did not directly correlate with the amount of NK activity generated, and interferon pretreatment of effectors did not decrease virus-specific cytotoxicity. The present results suggest that HSV-1 glycoproteins expressed at the surface of infected targets may act as recognition structures for NK cells.
Microwave tumors ablation: Principles, clinical applications and review of preliminary experiences
Authors: Gianpaolo Carrafiello, Domenico Laganà, Monica Mangini, Federico Fontana, Gianlorenzo Dionigi, Luigi Boni, Francesca Rovera, Salvatore Cuffari, Carlo Fugazzola
Journal: International Journal of Surgery (2008)

Local ablative techniques have been developed to enable local control of unresectable tumors. Ablation has been performed with several modalities including ethanol ablation, laser ablation, cryoablation, and radiofrequency ablation. Microwave technology is a new thermal ablation technique for different types of tumors, providing all the benefits of radiofrequency and substantial advantages. Microwave ablation has been applied to liver, lung, kidney and more rarely to bone, pancreas and adrenal glands. Preliminary works show that microwave ablation may be a viable alternative to other ablation techniques in selected patients. However further studies are necessary to confirm short- and long-term effectiveness of the methods and to compare it with other ablative techniques, especially RF.
Presenilins regulate αβ T cell development by modulating TCR signaling
Authors: Karen Laky, B.J. Fowlkes
Journal: The Journal of Experimental Medicine (2007)

TCRαβ signaling is crucial for the maturation of CD4 and CD8 T cells, but the role of the Notch signaling pathway in this process is poorly understood. Genes encoding Presenilin (PS) 1/2 were deleted to prevent activation of the multiple Notch receptors expressed by developing thymocytes. PS1/2 knockout thymocyte precursors inefficiently generate CD4 T cells, a phenotype that is most pronounced when thymocytes bear a single major histocompatibility complex (MHC) class II–restricted T cell receptor (TCR). Diminished T cell production correlated with evidence of impaired TCR signaling, and could be rescued by manipulations that enhance MHC recognition. Although Notch appears to directly regulate binary fate decisions in many systems, these findings suggest a model in which PS-dependent Notch signaling influences positive selection and the development of αβ T cells by modifying TCR signal transduction.
Conserved chromosomal clustering of genes governed by chromatin regulators in Drosophila
Authors: Enrique Blanco, Miguel Pignatelli, Sergi Beltran, Adrià Punset, Silvia Pérez-Lluch, Florenci Serras, Roderic Guigó, Montserrat Corominas
Journal: Genome biology (2008)

The trithorax group (trxG) and Polycomb group (PcG) proteins are responsible for the maintenance of stable transcriptional patterns of many developmental regulators. They bind to specific regions of DNA and direct the post-translational modifications of histones, playing a role in the dynamics of chromatin structure.We have performed genome-wide expression studies of trx and ash2 mutants in Drosophila melanogaster. Using computational analysis of our microarray data, we have identified 25 clusters of genes potentially regulated by TRX. Most of these clusters consist of genes that encode structural proteins involved in cuticle formation. This organization appears to be a distinctive feature of the regulatory networks of TRX and other chromatin regulators, since we have observed the same arrangement in clusters after experiments performed with ASH2, as well as in experiments performed by others with NURF, dMyc, and ASH1. We have also found many of these clusters to be significantly conserved in D. simulans, D. yakuba, D. pseudoobscura and partially in Anopheles gambiae.The analysis of genes governed by chromatin regulators has led to the identification of clusters of functionally related genes conserved in other insect species, suggesting this chromosomal organization is biologically important. Moreover, our results indicate that TRX and other chromatin regulators may act globally on chromatin domains that contain transcriptionally co-regulated genes.
Abstract 1173: HIF-1 promotes the infiltration of regulatory T cells into the tumor via TGF-β
Authors: Koji Teramoto, Yasuhiko Ohshio, Jun Hanaoka, Atsushi Takano, Yataro Daigo
Journal: Cancer Research (2014)

Abstract In the growing tumor under hypoxia, a transcription factor, hypoxia-inducible factor-1 (HIF-1) plays a critical role in regulating expressions of various genes associated with tumor growth. In order to elucidate the immunosuppression promoted by the hypoxic tumor microenvironment, we focused on a relationship between HIF-1 and an immunosuppressive cytokine, transforming growth factor-beta (TGF-β). TGF-β which is released from either tumor cells or tumor stromal cells and suppresses anti-tumor immune responses in tumor-bearing hosts may be regulated by HIF-1 in the hypoxic tumor microenvironment. In this report, we hypothesized that inhibition of HIF-1 in tumor cells would improve an immunosuppression to augment anti-tumor immune responses, and examined the possibilities in the tumor-bearing mice model. The transfected mouse lymphoma cells E.G7 with HIF-1 shRNA was administered to C57BL/6 mice subcutaneously at the flank. Three weeks later, anti-tumor immune responses elicited in the mice were examined. As results, in mice bearing the transfected E.G7 with HIF-1 shRNA, the protein level of TGF-β in the tumor tissue was decreased as compared with that in mice bearing the transfected E.G7 with control shRNA or the non-transfected E.G7. The infiltration of Foxp3+ cells in the tumor tissue was decreased in mice bearing the transfected E.G7 with HIF-1 shRNA. When spleen cells from those tumor-bearing mice were stimulated with E.G7-derived antigen, cytotoxic activity against target E.G7 cells were enhanced in mice bearing the transfected E.G7 with HIF-1 shRNA. While there were no significant differences in the cell proliferation between the transfected E.G7 cells with HIF-1 shRNA and those with control shRNA or non-transfected E.G7 cells in vitro, tumor growth was effectively suppressed in mice bearing the transfected E.G7 with HIF-1 shRNA. Inhibition of HIF-1 in tumor cells decreased the level of TGF-β in the hypoxic tumor microenvironment, leading to suppression of infiltrating Foxp3+ cells and improvement of anti-tumor immune responses. These results demonstrate that hypoxia in the tumor microenvironment is responsible for the induction of immunosuppression through the infiltration of regulatory T cells by TGF-β. Citation Format: Koji Teramoto, Yasuhiko Ohshio, Jun Hanaoka, Atsushi Takano, Yataro Daigo. HIF-1 promotes the infiltration of regulatory T cells into the tumor via TGF-β. [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 1173. doi:10.1158/1538-7445.AM2014-1173
Early Statin Treatment in Patients With Acute Coronary Syndrome
Authors: Shinya Okazaki, Takayuki Yokoyama, Katsumi Miyauchi, Kazunori Shimada, Takeshi Kurata, Hitoshi Sato, Hiroyuki Daida
Journal: Circulation (2004)

Recent clinical trials have demonstrated that aggressive lipid lowering by statins could prevent recurrent events after acute coronary syndrome (ACS). We hypothesized that this efficacy was caused by a significant reduction in plaque volume by aggressive LDL cholesterol (LCL-C) lowering. The present study investigated the effect of early statin treatment on plaque volume of a nonculprit lesion by serial volumetric intravascular ultrasound in patients with ACS.Seventy patients with ACS were enrolled. All patients underwent emergency coronary angiography and percutaneous coronary intervention (PCI). They were randomized to intensive lipid-lowering therapy (n=35; atorvastatin 20 mg/d) or control (n=35) groups after PCI. Volumetric intravascular ultrasound analyses were performed at baseline and 6-month follow-up for a non-PCI site in 48 patients (atorvastatin, n=24; control, n=24). LDL-C level was significantly decreased by 41.7% in the atorvastatin group compared with the control group, in which LDL-C was increased by 0.7% (P<0.0001). Plaque volume was significantly reduced in the atorvastatin group (13.1+/-12.8% decrease) compared with the control group (8.7+/-14.9% increase; P<0.0001). Percent change in plaque volume showed a significant positive correlation with follow-up LDL-C level (R=0.456, P=0.0011) and percent LDL-C reduction (R=0.612, P<0.0001), even in patients with baseline LDL-C <125 mg/dL.Early aggressive lipid-lowering therapy by atorvastatin for 6 months significantly reduced the plaque volume in patients with ACS. Percent change in plaque volume showed a significant positive correlation with percent LDL-C reduction, even in patients with low baseline LDL-C.
Pancreatitis: the neglected duct
Authors: M. G. Lee, S. Muallem
Journal: Gut (2008)

Acute and chronic pancreatitis are multifactorial diseases that involve inflammation of the pancreas, generation of toxic mediators and mistargeting of digestive enzymes that eventually result in destruction of the parenchyma.1 Because acinar cells contain the harmful mistargeted digestive enzymes and the extensive damage occurs in acinar cells in all forms and models of pancreatitis, research into the triggers and causes of pancreatitis have been focused on acinar cells.1 It is now well established that aberrant Ca2+ signalling leading to a sustained and prolonged increase in free cytoplasmic Ca2+ concentration ([Ca2+]i) is the nodal point in pancreatitis that perturbs many functions of acinar cells, leading to their destruction.

While undoubtedly destruction of acinar cells is the terminal step in pancreatitis, the duct is likely to play a crucial role in protecting the pancreas, and when this protection is compromised pancreatitis ensues. The central function of the pancreatic duct is the secretion of most of the fluid in the pancreatic juice and the coupled absorption of Cl– and secretion of HCO3– to generate juice containing as much as 140 mM HCO3–.2 The fluid is required to wash the harmful digestive enzymes away from the acinar lumen and ensure their exit from the pancreas. The HCO3– has several functions. Besides titrating part of the gastric acid in the duodenum, alkalinisation of the pancreatic juice by HCO3– prevents premature activation of digestive enzymes. Equally importantly, as a chaotropic ion HCO3– facilitates the solubilisation of divalent ions and of macromolecules, including the digestive enzymes and mucins, in the pancreatic juice.

The critical importance of fluid and HCO3– secretion by the pancreatic duct is evident from the inhibition of fluid and HCO3– …
PSYCHOSOCIAL FACTORS AND CARDIOVASCULAR DISEASES
Authors: Susan A. Everson-Rose, Tené T. Lewis
Journal: Annual Review of Public Health (2005)

Rapidly accruing evidence from a diversity of disciplines supports the hypothesis that psychosocial factors are related to morbidity and mortality due to cardiovascular diseases. We review relevant literature on (a) negative emotional states, including depression, anger and hostility, and anxiety; (b) chronic and acute psychosocial stressors; and (c) social ties, social support, and social conflict. All three of these psychosocial domains have been significantly associated with increased risk of cardiovascular morbidity and mortality. We also discuss critical pathophysiological mechanisms and pathways that likely operate in a synergistic and integrative way to promote atherogenesis and related clinical manifestations. We conclude by discussing some of the important challenges and opportunities for future investigations.
Microvolt T-Wave Alternans Distinguishes Between Patients Likely and Patients Not Likely to Benefit From Implanted Cardiac Defibrillator Therapy
Authors: Daniel M. Bloomfield, Richard C. Steinman, Pearila B. Namerow, Michael Parides, Jorge Davidenko, Elizabeth S. Kaufman, Timothy Shinn, Anne Curtis, John Fontaine, Douglas Holmes, Andrea Russo, Chuen Tang, J. Thomas Bigger
Journal: Circulation (2004)

Background— In 2003, the Centers for Medicaid and Medicare Services recommended QRS duration as a means to identify MADIT II–like patients suitable for implanted cardiac defibrillator (ICD) therapy. We compared the ability of microvolt T-wave alternans and QRS duration to identify groups at high and low risk of dying among heart failure patients who met MADIT II criteria for ICD prophylaxis. Methods and Results— Patients with MADIT II characteristics and sinus rhythm had a microvolt T-wave alternans exercise test and a 12-lead ECG. Our primary end point was 2-year all-cause mortality. Of 177 MADIT II–like patients, 32% had a QRS duration &gt;120 ms, and 68% had an abnormal (positive or indeterminate) microvolt T-wave alternans test. During an average follow-up of 20±6 months, 20 patients died. We compared patients with an abnormal microvolt T-wave alternans test to those with a normal (negative) test, and patients with a QRS &gt;120 ms with those with a QRS ≤120 ms; the hazard ratios for 2-year mortality were 4.8 ( P =0.020) and 1.5 ( P =0.367), respectively. The actuarial mortality rate was substantially lower among patients with a normal microvolt T-wave alternans test (3.8%; 95% confidence interval: 0, 9.0) than the mortality rate in patients with a narrow QRS (12.0%; 95% confidence interval: 5.6, 18.5). The corresponding false-negative rates are 3.5% and 10.2%, respectively. Conclusion— Among MADIT II–like patients, a microvolt T-wave alternans test is better than QRS duration at identifying a high-risk group and also better at identifying a low-risk group unlikely to benefit from ICD therapy.
Effect of lower limb massage on electromyography and force production of the knee extensors
Authors: A M Hunter, J M Watt, V Watt, S D R Galloway
Journal: British Journal of Sports Medicine (2006)

To evaluate the effect of massage on force production and neuromuscular recruitment.Ten healthy male subjects performed isokinetic concentric contractions on the knee extensors at speeds of 60, 120, 180, and 240 degrees /s. These contractions were performed before and after a 30 minute intervention of either rest in the supine position or lower limb massage. Electromyography (EMG) and force data were captured during the contractions.The change in isokinetic mean force due to the intervention showed a significant decrease (p<0.05) at 60 degrees /s and a trend for a decrease (p = 0.08) at 120 degrees /s as a result of massage compared with passive rest. However, there were no corresponding differences in any of the EMG data. A reduction in force production was shown at 60 degrees /s with no corresponding alteration in neuromuscular activity.The results suggests that motor unit recruitment and muscle fibre conduction velocity are not responsible for the observed reductions in force. Although experimental confirmation is necessary, a possible explanation is that massage induced force loss by influencing "muscle architecture". However, it is possible that the differences were only found at 60 degrees /s because it was the first contraction after massage. Therefore muscle tension and architecture after massage and the duration of any massage effect need to be examined.
Macromolecular properties that promote mesangial binding and mesangiopathic nephritis.
Authors: S N Emancipator, C S Rao, A Amore, R Coppo, J G Nedrud
Journal: Journal of the American Society of Nephrology (1992)

The hydrodynamic size, electrostatic charge, and specificity are established determinants of the site of glomerular localization of macromolecules. Larger macromolecules or aggregates and anionic charge are associated with mesangial deposits, despite the fact that the mesangial matrix bears a negative charge similar to that of the capillary wall. Antigens such as Sendai virus, a model infectious pathogen, gliadin, a model dietary/environmental agent and fibronectin, a model endogenous macromolecule, bind to mesangial cells in vitro on the basis of cell surface glycoconjugates. Nonantibody immunoglobulin A, which does not bind to cells directly, binds to these elements via different carbohydrate specificities (simple sugar inhibition). Such binding promotes or augments macromolecular deposition in the mesangium. More significantly, mesangial deposits per se are not pathogenic, because normal renal function can be observed with florid deposits. Pathogenic deposits must have properties that alter mesangial cell metabolism or interaction with the matrix. Although complement activation is well recognized, complement-independent mechanisms related to cell surface modulation are being recognized. In vitro, antigen/immunoglobulin A aggregates alter mesangial cell eicosanoid synthesis. In vivo, large-lattice cross-linking by particulate antigen promotes hematuria. We conclude that the binding of macromolecules to cells and the cross-linking of cell surface molecules cause alterations in the mesangial cells and therefore in glomerular function. The mesangial cell, rather than a passive respondent, is an active participant in the genesis of glomerulonephritis.
Splanchnic exchange of glucose, amino acids and free fatty acids in patients with chronic inflammatory bowel disease.
Authors: L S Eriksson
Journal: Gut (1983)

In order to study arterial concentrations and splanchnic exchange of substrates and hormones in patients with chronic inflammatory bowel disease three patients with Crohn9s disease and four with ulcerative colitis were studied using the hepatic venous catheter technique. Systemic turnover and regional exchange of free fatty acid were evaluated using intravenous infusion of 14C-labelled oleic acid. All measurements were made in the postabsorptive, overnight fasted state. Arterial glucose concentrations were 10% lower in the patients but net splanchnic glucose output was similar in patients and controls. Glucose precursor uptake (lactate, pyruvate, and glycerol), however, was increased two to five fold in the patients. Arterial amino acid concentrations were generally reduced but net splanchnic amino acid uptake was the same in patients and controls. Arterial concentrations of free fatty acid and oleic acid as well as systemic and fractional turnover were similar in patients and controls. The patients9 splanchnic uptake of oleic acid was increased more than three fold in comparison with controls. Splanchnic release of oleic acid was also augmented in the patients. Both arterial concentrations and splanchnic production of ketone bodies were raised in the patients. The proportion of splanchnic free fatty acid uptake which could be accounted for by ketone body production was significantly greater in the patients (37 +/- 4%) than the controls (20 +/- 5%, p less than 0.025). Estimated hepatic blood flow was 55% greater (p less than 0.01) in the patients as compared with the controls (1930 +/- 150 vs 1240 +/- 70 ml/min), while splanchnic oxygen uptake was similar in the two groups. From these findings it is concluded that patients with chronic inflammatory bowel disease show (1) markedly increased hepatic blood flow, reflecting an inflammatory hyperaemia in the splanchnic region, (2) a normal net splanchnic glucose output, (3) accelerated hepatic gluconeogenesis as well as ketogenesis, probably as a consequence of the altered hormonal milieau, and (4) low concentrations of most amino acids possibly because of protein malabsorption. These findings underscore the importance of adequate protein and carbohydrate administration to this patient group.
Viral Subversion of the Immune System
Authors: Domenico Tortorella, Benjamin E. Gewurz, Margo H. Furman, Danny J. Schust, Hidde L. Ploegh
Journal: Annual Review of Immunology (2000)

This review describes the diverse array of pathways and molecular targets that are used by viruses to elude immune detection and destruction. These include targeting of pathways for major histocompatibility complex-restricted antigen presentation, apoptosis, cytokine-mediated signaling, and humoral immune responses. The continuous interactions between host and pathogens during their coevolution have shaped the immune system, but also the counter measures used by pathogens. Further study of their interactions should improve our ability to manipulate and exploit the various pathogens.