tbuckley/cabot-search huggingface dataset:
Interleukin-18 Enhances Atherosclerosis in Apolipoprotein E <sup>−/−</sup> Mice Through Release of Interferon-γ
Authors: Stewart C. Whitman, Punnaivanam Ravisankar, Alan Daugherty
Journal: Circulation Research (2002)

We have previously shown that interferon-γ (IFN-γ) is a potent enhancer of atherogenesis. Interleukin-18 (IL-18) promotes inflammatory responses through release of IFN-γ, although it can also exert direct actions on other inflammatory mediators. In this present study, we determined the effects of IL-18 on atherogenesis and the role of IFN-γ in this response. Male apolipoprotein E −/− mice ( apo e −/− ; aged 16 weeks, n=10/group) were fed a normal diet and injected intraperitoneally for 30 days with either recombinant IL-18 (30 ng/g/day) or saline. Atherosclerotic lesion size was quantified in 2 vascular beds: the ascending aorta and the aortic arch. IL-18 administration did not affect serum cholesterol concentrations or lipoprotein-cholesterol distribution; however, exogenous IL-18 administration increased lesion size 2-fold in both the ascending aorta (50 642±12 515 versus 112 399±13 227 μm 2 , P =0.004; saline versus IL-18 groups, respectively) and the aortic arch (3.1±0.3% versus 6.2±0.9% area, P =0.006). Exogenous IL-18 promoted a 4-fold increase in the number of lesion-associated T lymphocytes (11±3 versus 50±5 cells; P &lt;0.0001) and cells expressing major histocompatability complex class II (9±3 versus 40±6 cells; P =0.0002). To determine the role of IFN-γ production in this response, exogenous IL-18 was administered to apo e −/− mice that were IFN-γ deficient. These studies demonstrated that lack of endogenous IFN-γ ablated the effects of IL-18 on atherosclerosis. Therefore, these data strongly implicates IL-18 in the atherogenic process and suggests that IL-18 increases lesion development through enhancement of an inflammatory response involving an IFN-γ–dependent mechanism. The full text of this article is available at http://www.circresaha.org.
Metalloproteinase-mediated release of human Fas ligand.
Authors: N Kayagaki, A Kawasaki, T Ebata, H Ohmoto, S Ikeda, S Inoue, K Yoshino, K Okumura, H Yagita
Journal: The Journal of Experimental Medicine (1995)

Fas ligand (FasL) is a type II integral membrane protein homologous with tumor necrosis factor (TNF). Recent studies indicate that TNF is processed to yield the soluble cytokine by metalloproteinases at the cell surface of activated macrophages and T cells. In the present study, we investigated whether FasL is also released by metalloproteinases. Treatment with hydroxamic acid inhibitors of matrix metalloproteinases specifically led to accumulation of membrane-type FasL (p40) on the surface of human FasL cDNA transfectants and activated human T cells, as estimated by surface immunofluorescence and immunoprecipitation with newly established anti-human FasL monoclonal antibodies. This surface accumulation of mFasL was associated with the decrease of soluble FasL (p27) in the supernatant as estimated by quantitative ELISA and immunoprecipitation with anti-human FasL monoclonal antibodies. These results indicate that human FasL is efficiently released from the cell surface by metalloproteinases like TNF.
Triple therapy with amantadine sulphate plus ribavirin and interferon-alpha in previously untreated patients with chronic hepatitis C: results of a double-blind, placebo-controlled trial
Authors: Thomas Berg, Bernd Kronenberger, Holger Hinrichsen, Tilman Gerlach, Peter Buggisch, Ulrich Spengler, Tobias Goeser, Gerd Pape, Uwe Hopf, Stefan Zeuzem
Journal: Journal of Hepatology (2002)
Robotically Assisted vs Laparoscopic Hysterectomy Among Women With Benign Gynecologic Disease
Authors: Jason D Wright, Cande V Ananth, Sharyn N Lewin, William M Burke, Yu-Shiang Lu, Alfred I Neugut, Thomas J Herzog, Dawn L Hershman
Journal: JAMA (2013)

Although robotically assisted hysterectomy for benign gynecologic conditions has been reported, little is known about the incorporation of the procedure into practice, its complication profile, or its costs compared with other routes of hysterectomy.To analyze the uptake of robotically assisted hysterectomy, to determine the association between use of robotic surgery and rates of abdominal and laparoscopic hysterectomy, and to compare the in-house complications of robotically assisted hysterectomy vs abdominal and laparoscopic procedures.Cohort study of 264,758 women who underwent hysterectomy for benign gynecologic disorders at 441 hospitals across the United States from 2007 to 2010.Uptake of and factors associated with utilization of robotically assisted hysterectomy. Complications, transfusion, reoperation, length of stay, death, and cost for women who underwent robotic hysterectomy compared with both abdominal and laparoscopic procedures were analyzed.Use of robotically assisted hysterectomy increased from 0.5% in 2007 to 9.5% of all hysterectomies in 2010. During the same time period, laparoscopic hysterectomy rates increased from 24.3% to 30.5%. Three years after the first robotic procedure at hospitals where robotically assisted hysterectomy was performed, robotically assisted hysterectomy accounted for 22.4% of all hysterectomies. The rates of abdominal hysterectomy decreased both in hospitals where robotic-assisted hysterectomy was performed as well as in those where it was not performed. In a propensity score-matched analysis, the overall complication rates were similar for robotic-assisted and laparoscopic hysterectomy (5.5% vs 5.3%; relative risk [RR], 1.03; 95% CI, 0.86-1.24). Although patients who underwent a robotic-assisted hysterectomy were less likely to have a length of stay longer than 2 days (19.6% vs 24.9%; RR, 0.78, 95% CI, 0.67-0.92), transfusion requirements (1.4% vs 1.8%; RR, 0.80; 95% CI, 0.55-1.16) and the rate of discharge to a nursing facility (0.2% vs 0.3%; RR, 0.79; 95% CI, 0.35-1.76) were similar. Total costs associated with robotically assisted hysterectomy were $2189 (95% CI, $2030-$2349) more per case than for laparoscopic hysterectomy.Between 2007 and 2010, the use of robotically assisted hysterectomy for benign gynecologic disorders increased substantially. Robotically assisted and laparoscopic hysterectomy had similar morbidity profiles, but the use of robotic technology resulted in substantially more costs.
Urinary 6-Sulfatoxymelatonin Levels and Risk of Breast Cancer in Postmenopausal Women
Authors: E. S. Schernhammer, F. Berrino, V. Krogh, G. Secreto, A. Micheli, E. Venturelli, S. Sieri, C. T. Sempos, A. Cavalleri, H. J. Schunemann, S. Strano, P. Muti
Journal: JNCI Journal of the National Cancer Institute (2008)

Low urinary melatonin levels have been associated with an increased risk of breast cancer in premenopausal women. However, the association between melatonin levels and breast cancer risk in postmenopausal women remains unclear.We investigated the association between melatonin levels and breast cancer risk in postmenopausal women in a prospective case-control study nested in the Hormones and Diet in the Etiology of Breast Cancer Risk cohort, which included 3966 eligible postmenopausal women. The concentration of melatonin's major metabolite, 6-sulfatoxymelatonin, was measured in a baseline 12-hour overnight urine sample from 178 women who later developed incident breast cancer and from 710 matched control subjects. We used multivariable-adjusted conditional logistic regression models to investigate associations. Relative risks are reported as odds ratios (ORs). All statistical tests were two-sided.Increased melatonin levels were associated with a statistically significantly lower risk of invasive breast cancer in postmenopausal women (for women in the highest quartile of total overnight 6-sulfatoxymelatonin output vs the lowest quartile, multivariable OR also adjusted for testosterone = 0.56, 95% confidence interval [CI] = 0.33 to 0.97; P(trend) = .02). This association was strongest among never and past smokers (OR = 0.38, 95% CI = 0.20 to 0.74; P(trend) = .001) and after excluding women who were diagnosed with invasive breast cancer within 4 years after urine collection (OR = 0.34, 95% CI = 0.15 to 0.75; P(trend) = .002). We did not observe substantial variation in relative risks by hormone receptor status of breast tumors. Among the 3966 women in the cohort, 40 of the 992 women in the highest quartile of 6-sulfatoxymelatonin developed breast cancer during follow-up, compared with 56 of the 992 women in the lowest quartile of 6-sulfatoxymelatonin.Results from this prospective study provide evidence for a statistically significant inverse association between melatonin levels, as measured in overnight morning urine, and invasive breast cancer risk in postmenopausal women.
Expression of p53R2 Is Related to Prognosis in Patients with Esophageal Squamous Cell Carcinoma
Authors: Hiroshi Okumura, Shoji Natsugoe, Naoya Yokomakura, Yoshiaki Kita, Masataka Matsumoto, Yasuto Uchikado, Tetsuro Setoyama, Tetsuhiro Owaki, Sumiya Ishigami, Takashi Aikou
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The p53 gene and its family are important factors for carcinogenesis, prognosis, and chemoresistance in esophageal squamous cell carcinoma. A recently identified ribonucleotide reductase, p53R2, is regulated by p53 for supplying nucleotides to repair damaged DNA. In the present study, we analyzed the expression and clinicopathologic significance of p53 and p53R2 in esophageal squamous cell carcinoma. Experimental Design: We immunohistochemically investigated the relationship between p53 and p53R2 expressions in surgical specimens of primary tumors in 222 patients with esophageal squamous cell carcinoma. Results: The positive expression rate of p53 was 47.1% and that of p53R2 was 61.7%. Positive p53R2 expression was significantly correlated with depth of invasion, lymph node metastasis, stage, and poor prognosis. In the p53-negative group, the 5-year survival rate was better in patients with negative p53R2 expression than in those with positive p53R2 expression. Multivariate analysis indicated that the negative expression of both p53 and p53R2 was an independent prognostic factor along with tumor depth nodal metastasis and stage. Conclusions: We showed that positive p53R2 expression was related to tumor development and that alteration of p53R2 expression in p53-negative tumors was closely related to prognosis. Evaluation of the expressions of p53 and p53R2 proteins should be useful for determining the tumor properties, including prognosis, in patients with esophageal squamous cell carcinoma.
Evidence for conserved post-transcriptional roles of unitary pseudogenes and for frequent bifunctionality of mRNAs
Authors: Ana C Marques, Jennifer Tan, Sheena Lee, Lesheng Kong, Andreas Heger, Chris P Ponting
Journal: Genome biology (2012)

Abstract Background Recent reports have highlighted instances of mRNAs that, in addition to coding for protein, regulate the abundance of related transcripts by altering microRNA availability. These two mRNA roles - one mediated by RNA and the other by protein - are inter-dependent and hence cannot easily be separated. Whether the RNA-mediated role of transcripts is important, per se , or whether it is a relatively innocuous consequence of competition by different transcripts for microRNA binding remains unknown. Results Here we took advantage of 48 loci that encoded proteins in the earliest eutherian ancestor, but whose protein-coding capability has since been lost specifically during rodent evolution. Sixty-five percent of such loci, which we term 'unitary pseudogenes', have retained their expression in mouse and their transcripts exhibit conserved tissue expression profiles. The maintenance of these unitary pseudogenes' spatial expression profiles is associated with conservation of their microRNA response elements and these appear to preserve the post-transcriptional roles of their protein-coding ancestor. We used mouse Pbcas4 , an exemplar of these transcribed unitary pseudogenes, to experimentally test our genome-wide predictions. We demonstrate that the role of Pbcas4 as a competitive endogenous RNA has been conserved and has outlived its ancestral gene's loss of protein-coding potential. Conclusions These results show that post-transcriptional regulation by bifunctional mRNAs can persist over long evolutionary time periods even after their protein coding ability has been lost.
A novel method to determine small intestinal barrier function in human neonates in vivo
Authors: M W Schaart
Journal: Gut (2006)

reduction in total ERCP numbers was found in the post-MRCP period and the monthly mean number of ERCPs performed was reduced from 22 to 17 per month.Cannulation failure rates pre-MRCP and post-MRCP were 8.7% (26 ERCPs) and 14.2% (33 ERCPs), respectively.Pre-MRCP introduction, 191 of 272 (70%) successful cannulations were with therapeutic intent.Post-MRCP introduction, 163 of 232 (81%) successful cannulations were with therapeutic intent.Significant increases in the proportion of therapeutic procedures (odds ratio (OR) 1.74 (95% confidence interval (CI) 1.13-2.69);p = 0.012) and failed cannulations (OR 1.74 (95% CI 1.005-2.99);p = 0.046) were therefore identified.No significant associations existed between each ERCP indication and failed cannulation.Changes in therapeutic intervention following MRCP introduction for each indication are highlighted in table 1.We have encountered alterations in ERCP practice following MRCP introduction with fewer, potentially more complex, procedures being performed.Subset analysis found change only in the group with pain, biliary dilatation, with abnormal LFTs¡CBD stone on USS, potentially reflecting improved identification of duct stones by MRCP.Objective assessment of technical difficulty was not easy, as both trainees and trainers were both involved in performing ERCPs and no validated criteria to assess ERCP difficulty were available during the study period.MRCP introduction has an impact on ERCP practice.ERCP services and training may require redirection towards fewer but more complex procedures.These changes may necessitate a reduction in the number of cases performed on a list, may result in fewer trainees embarking on ERCP training and, as endoscopy centres require threshold numbers of cases to ensure competency in technique and adequacy of training, may reduce the number of centres able to offer viable training opportunities.
An Open Letter to Institutional Review Boards Considering Northfield Laboratories’ PolyHeme® Trial
Authors: Ken Kipnis, Nancy M. P. King, Robert M. Nelson
Journal: The American Journal of Bioethics (2010)

At the time of this writing, a widely publicized, waived-consent trial is underway. Sponsored by Northfield Laboratories, Inc. (Evanston, IL) the trial is intended to evaluate the emergency use of PolyHeme®, an oxygen-carrying resuscitative fluid that might prevent deaths from uncontrolled bleeding. The protocol allows patients in hemorrhagic shock to be randomized between PolyHeme® and saline in the field and, still without consent, randomized between PolyHeme® and blood after arrival at an emergency department. The Federal regulations that govern the waiver of consent restrict its applicability to circumstances where proven, satisfactory treatments are unavailable. Blood—the standard treatment for hemorrhagic shock—is not available in ambulances but is available in hospitals. The authors argue that the in-hospital stage of the study fails to meet ethical and regulatory standards.
Immune phagocytosis in murine malaria.
Authors: H L Shear, R S Nussenzweig, C Bianco
Journal: The Journal of Experimental Medicine (1979)

Spleen macrophages from Plasmodium berghei-infected mice are more efficient in the ingestion of parasitized reticulocytes than spleen macrophages obtained from normal animals. Other indications of spleen macrophage activation detected during malarial infection are enhanced macrophage spreading and increased phagocytosis of opsonized and nonopsonized sheep erythrocytes (E). Peritoneal macrophages are not activated to a significant degree. The appearance of antibodies directed against Forssman antigen, but not to other erythrocyte antigens, is also a feature of this infection and explains the ingestion of unsensitized E by spleen macrophages of the diseased animals. The recognition and ingestion of parasitized reticulocytes by infected mice in mediated by cold-agglutinin type immunoglobulins that appear during P. berghei infection and can be blocked by the Fc-binding protein A from Staphylococcus aureus. In advanced stages of the disease, the serum of infected animals inhibits phagocytosis, probably because of the high level of circulating immune complexes. Thus, the clearance of malaria parasites is regulated by several elements of the immune system, in addition to levels of specific antimerozoite antibodies, including the amount of antibodies bound to reticulocytes, the presence of circulating immune complexes, and the degree of macrophage stimulation.
HIC1 Silencing in Triple-Negative Breast Cancer Drives Progression through Misregulation of LCN2
Authors: Guangcun Cheng, Xueqing Sun, Jinglong Wang, Gang Xiao, Xiumin Wang, Xuemei Fan, Lidong Zu, Mingang Hao, Qing Qu, Yan Mao, Yunjing Xue, Jianhua Wang
Journal: Cancer Research (2013)

Abstract The tumor suppressor gene HIC1 is frequently deleted or epigenetically silenced in human cancer, where its restoration may improve cancer prognosis. Here, we report results illuminating how HIC1 silencing alters effect or signals in triple-negative breast cancer (TNBC), which are crucial for its pathogenesis. HIC1 expression was silenced only in TNBC compared with other molecular subtypes of breast cancer. Restoring HIC1 expression in TNBC cells reduced cell migration, invasion, and metastasis, whereas RNAi-mediated silencing of HIC1 in untransformed human breast cells increased their invasive capabilities. Mechanistic investigations identified the small-secreted protein lipocalin-2 (LCN2), as a critical downstream target of HIC1 in TNBC cells. Elevating LCN2 expression in cells expressing HIC1 partially rescued its suppression of cell invasion and metastasis. Notably, autocrine secretion of LCN2 induced by loss of HIC1 activated the AKT pathway through the neutrophil gelatinase–associated lipocalin receptor, which is associated with TNBC progression. Taken together, our findings revealed that the HIC1–LCN2 axis may serve as a subtype-specific prognostic biomarker, providing an appealing candidate target for TNBC therapy. Cancer Res; 74(3); 862–72. ©2013 AACR.
Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture.
Authors: P R Moreno, E Falk, I F Palacios, J B Newell, V Fuster, J T Fallon
Journal: Circulation (1994)

BACKGROUND Rupture of atherosclerotic plaques is probably the most important mechanism underlying the sudden onset of acute coronary syndromes. Macrophages may release lytic enzymes that degrade the fibrous cap and therefore produce rupture of the atherosclerotic plaque. This study was designed to quantify macrophage content in coronary plaque tissue from patients with stable and unstable coronary syndromes. METHODS AND RESULTS Hematoxylin and eosin and immunostaining with anti-human macrophage monoclonal antibody (PG-M1) were performed. Computerized planimetry was used to analyze 26 atherectomy specimens comprising 524 pieces of tissue from 8 patients with chronic stable angina, 8 patients with unstable angina, and 10 patients with non-Q-wave myocardial infarction. Total plaque area was 417 +/- 87 mm2 x 10(-2) in patients with stable angina, 601 +/- 157 mm2 x 10(-2) in patients with unstable angina, and 499 +/- 87 mm2 x 10(-2) in patients with non-Q-wave myocardial infarction (P = NS). The macrophage-rich area was larger in plaques from patients with unstable angina (61 +/- 18 mm2 x 10(-2)) and non-Q-wave myocardial infarction (87 +/- 32 mm2 x 10(-2)) than in plaques from patients with stable angina (14 +/- 5 mm2 x 10(-2)) (P = .024). The percentage of the total plaque area occupied by macrophages was also larger in patients with unstable angina (13.3 +/- 5.6%) and non-Q-wave myocardial infarction (14.6 +/- 4.6%) than in patients with stable angina (3.14 +/- 1%) (P = .018). Macrophage-rich sclerotic tissue was largest in patients with non-Q-wave myocardial infarction (67 +/- 30 mm2 x 10(-2)) and unstable angina (55 +/- 19 mm2 x 10(-2)) than in patients with stable angina (11.5 +/- 4.1 mm2 x 10(-2)) (P = .046). Macrophage-rich atheromatous gruel was also largest in patients with non-Q-wave myocardial infarction (15 +/- 4 mm2 x 10(-2)) than in patients with unstable angina (3.3 +/- 1.7 mm2 x 10(-2)) or stable angina (2.4 +/- 1.2 mm2 x 10(-2)) (P = .026). CONCLUSIONS Macrophage-rich areas are more frequently found in patients with unstable angina and non-Q-wave myocardial infarction. This suggests that macrophages are a marker of unstable atherosclerotic plaques and may play a significant role in the pathophysiology of acute coronary syndromes.
Effects of chemical feedback on respiratory motor and ventilatory output during different modes of assisted mechanical ventilation
Authors: J Mitrouska, N Xirouchaki, D Patakas, N Siafakas, D Georgopoulos
Journal: European Respiratory Journal (1999)

The purpose of the study was to examine the effects of chemical feedback on respiratory motor and ventilatory output in conscious subjects ventilated on various modes of assisted mechanical ventilation. Seven subjects were connected to a ventilator and randomly ventilated on assist-volume control (AVC), pressure support (PS) or proportional assist ventilation (PAV). On each mode, the assist level was set to the highest comfortable level. Airway and oesophageal (Poes) pressures, tidal volume, respiratory frequency (fR) and end-tidal carbon dioxide tension (PET,CO2) were measured breath-by-breath. When the subjects were stable on each mode, the fraction of inspired carbon dioxide (FI,CO2) was increased stepwise, and changes in minute ventilation (V'E) and respiratory motor output, estimated by the pressure-time product of all the respiratory muscles per breath (PTPrm) and per minute (PTPminute), were observed. At zero FI,CO2, PTPminute/PET,CO2 did not differ between modes, while V'E/ PTPminute was significantly lower with PAV than that with PS and AVC. As a result V'E/PET,CO2 was significantly lower with PAV, preventing, unlike AVC and PS, a significant drop in PET,CO2. With PAV, independent of CO2, V'E/PTPminute remained constant, while it decreased significantly with increasing CO2 stimulus with PS and AVC. At high PET,CO2 respiratory effort was significantly lower with PAV than that with PS and AVC. In conclusion, the mode of mechanical ventilation modifies the effects of chemical feedback on respiratory motor and ventilatory output. At all carbon dioxide stimulus levels neuroventilatory coupling was better preserved with proportional assist ventilation than with pressure support and assist-volume control ventilation.