tbuckley/cabot-search huggingface dataset:
Biliary secretion of fluid-phase markers by the isolated perfused rat liver. Role of transcellular vesicular transport.
Authors: J R Lake, V Licko, R W Van Dyke, B F Scharschmidt
Journal: Journal of Clinical Investigation (1985)

In these studies, we have used several approaches to systematically explore the contribution of transcellular vesicular transport (transcytosis) to the blood-to-bile movement of inert fluid-phase markers of widely varying molecular weight. First, under steady-state conditions, the perfused rat liver secreted even large markers in appreciable amounts. The bile-to-plasma (B/P) ratio of these different markers, including microperoxidase (B/P ratio = 0.06; mol wt = 1,879), insulin (B/P ratio = 0.09, mol wt = 5,000), horseradish peroxidase (B/P ratio = 0.04, mol wt = 40,000), and dextran (B/P ratio = 0.09, mol wt = 70,000), exhibited no clear ordering based on size alone, and when dextrans of two different sizes (40,000 and 70,000 mol wt) were studied simultaneously, the relative amounts of the two dextran species in bile were the same as in perfusate. Taurocholate administration produced a 71% increase in bile flow but little or no (0-20%) increase in the output of horseradish peroxidase, microperoxidase, inulin, and dextran. Second, under nonsteady-state conditions in which the appearance in or disappearance from bile of selected markers was studied after their abrupt addition to or removal from perfusate, erythritol reached a B/P ratio of 1 within 2 min. Microperoxidase and dextran appeared in bile only after a lag period of approximately 12 min and then slowly approached maximal values, whereas sucrose exhibited kinetically intermediate behavior. A similar pattern was observed after removal of greater than 95% of the marker from the perfusate. Erythritol rapidly reapproached a B/P ratio of 1, whereas the B/P ratio for sucrose, dextran, and microperoxidase fell much more slowly and exceeded 1 for a full 30 min after perfusate washout. Finally, electron microscopy and fluorescence microscopy of cultured hepatocytes demonstrated the presence of horseradish peroxidase and fluorescein-dextran, respectively, in intracellular vesicles, and fractionation of perfused liver homogenates revealed that at least 35-50% of sucrose, inulin, and dextran was associated with subcellular organelles. Collectively, these observations are most compatible with a transcytosis pathway that contributes minimally to the secretion of erythritol, but accounts for a substantial fraction of sucrose secretion and virtually all (greater than 95%) of the blood-to-bile transport of microperoxidase and larger markers. These findings have important implications with respect to current concepts of canalicular bile formation as well as with respect to the conventional use of solutes such as sucrose as markers of canalicular or paracellular pathway permeability.
The Prevalence of Gastroesophageal Reflux in Asthma Patients without Reflux Symptoms
Authors: SUSAN M. HARDING, MELANY R. GUZZO, JOEL E. RICHTER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Gastroesophageal reflux is a potential trigger of asthma that may be clinically silent. This study examines the prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. This prospective cohort study evaluated 26 patients with stable asthma without reflux symptoms using esophageal manometry and 24-h esophageal pH testing. Gastroesophageal reflux was considered present if esophageal acid contact times were abnormal. Demographic variables were analyzed to determine if they predicted the presence of gastroesophageal reflux. Asthma patients with asymptomatic gastroesophageal reflux were compared with 30 age-matched asthma patients with symptomatic gastroesophageal reflux. The prevalence of abnormal 24-h esophageal pH tests in asthma patients without reflux symptoms was 62% (16 of 26). Demographic variables did not predict abnormal 24-h esophageal pH tests in asthma patients with asymptomatic gastroesophageal reflux. Asthma patients with asymptomatic gastroesophageal reflux had higher amounts of proximal esophageal acid exposure (p < 0.05) compared with asthma patients with symptomatic gastroesophageal reflux. Because demographic variables do not predict abnormal 24-h esophageal pH tests in asthma patients without reflux symptoms, 24-h esophageal pH testing is required. This study suggests that gastroesophageal reflux is present in asthma patients, even in the absence of esophageal symptoms.
Magnetic Resonance–Guided Placement of Atrial Septal Closure Device in Animal Model of Patent Foramen Ovale
Authors: Arno Buecker, Elmar Spuentrup, Ralph Grabitz, Franz Freudenthal, Eberhard G. Muehler, Tobias Schaeffter, Joop J. van Vaals, Rolf W. Günther
Journal: Circulation (2002)

Background — Percutaneous closure of the patent foramen ovale (PFO) is usually performed under x-ray in combination with ultrasound guidance. We tested the feasibility of applying magnetic resonance (MR) guidance for percutaneous closure of PFO in an animal model, thus avoiding the disadvantage of ionizing radiation. Methods and Results — Real-time MRI with radial or spiral k-space filling (15 frames per second) on an interventional 1.5-T high-field whole-body system was exploited to examine the feasibility of MR-guided closure of the PFO in 7 piglets weighing ≈14 kg. A specially designed prototype nonmagnetic closure device was introduced via the femoral vein. The short bore of the magnet and in-room monitors allowed for visualization and steering of the catheter with the loaded occluder. Catheterization of the left atrium and, finally, correct placement of the device was possible in all animals. Deployment of the device was depicted by real-time MR, and initial misplacement, which occurred in 2 animals, was easily detected and corrected. Conclusions — Real-time MR guidance of PFO closure, without the use of ionizing radiation, is feasible in an animal model.
Late Onset of Treatment with a Chemokine Receptor CCR1 Antagonist Prevents Progression of Lupus Nephritis in MRL-Fas(lpr) Mice
Authors: Hans-Joachim Anders, Emilia Belemezova, Vaclav Eis, Stephan Segerer, Volker Vielhauer, Guillermo Perez de Lema, Matthias Kretzler, Clemens D. Cohen, Michael Frink, Richard Horuk, Kelly L. Hudkins, Charles E. Alpers, Francisco Mampaso, Detlef Schlo[Combining Diaeresis]ndorff
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Slowly progressive renal injury is the major cause for ESRD. The model of progressive immune complex glomerulonephritis in autoimmune MRL<sup>lpr/lpr</sup> mice was used to evaluate whether chemokine receptor CCR1 blockade late in the disease course can affect progression to renal failure. Mice were treated with subcutaneous injections of either vehicle or BX471, a nonpeptide CCR1 antagonist, three times a week from week 20 to 24 of age. BX471 improved blood urea nitrogen levels (BX471, 35.1 ± 5.3; vehicle, 73.1 ± 39.6 mg/dl; <i>P</i> &lt; 0.05) and reduced the amount of ERHR-3 macrophages, CD3 lymphocytes, Ki-67 positive proliferating cells, and ssDNA positive apoptotic cells in the interstitium but not in glomeruli. Cell transfer studies with fluorescence-labeled T cells that were pretreated with either vehicle or BX471 showed that BX471 blocks macrophage and T cell recruitment to the renal interstitium of MRL<sup>lpr/lpr</sup> mice. This was associated with reduced renal expression of CC chemokines CCL2, CCL3, CCL4, and CCL5 and the chemokine receptors CCR1, CCR2, and CCR5. Furthermore, BX471 reduced the extent of interstitial fibrosis as evaluated by interstitial smooth muscle actin expression and collagen I deposits, as well as mRNA expression for collagen I and TGF-β. BX471 did not affect serum DNA autoantibodies, proteinuria, or markers of glomerular injury in MRL<sup>lpr/lpr</sup> mice. This is the first evidence that, in advanced chronic renal injury, blockade of CCR1 can halt disease progression and improve renal function by selective inhibition of interstitial leukocyte recruitment and fibrosis.
Noncoding RNAs in Cardiovascular Biology and Disease
Authors: Priyatansh Gurha, Ali J. Marian
Journal: Circulation Research (2013)

The goal of "Recent Developments" is to provide a concise but comprehensive overview of new advances in cardiovascular research, which we hope will keep our readers abreast of recent scientific discoveries and facilitate discussion, interpretation, and integration of the findings.This will enable readers who are not experts in a particular field to grasp the significance and impact of work performed in other fields.It is our hope and expectation that these "Recent Developments" articles will help readers to gain a broader awareness and a deeper understanding of the status of research across the vast landscape of cardiovascular research.
Use of Survivorship Care Plans in the United States: Associations With Survivorship Care
Authors: L. P. Forsythe, C. Parry, C. M. Alfano, E. E. Kent, C. R. Leach, D. A. Haggstrom, P. A. Ganz, N. Aziz, J. H. Rowland
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundSurvivorship care plans (SCPs), including a treatment summary and follow-up plan, intend to promote coordination of posttreatment cancer care; yet, little is known about the provision of these documents by oncologists to primary care physicians (PCPs). This study compared self-reported oncologist provision and PCP receipt of treatment summaries and follow-up plans, characterized oncologists who reported consistent provision of these documents to PCPs, and examined associations between PCP receipt of these documents and survivorship care.
Do sputum eosinophils and ECP relate to the severity of asthma?
Authors: MC Ronchi, C Piragino, E Rosi, L Stendardi, A Tanini, G Galli, R Duranti, G Scano
Journal: European Respiratory Journal (1997)

There is much evidence that eosinophils play an important role in bronchial epithelial damage in asthma by releasing cationic proteins. However, the extent to which eosinophil inflammation relates to indices of asthma severity in chronic stable asthma is still a matter of debate. We studied 46 clinically stable patients with mild to severe chronic asthma (forced expiratory volume in one second (FEV1) 50-126% of predicted value). The clinical severity of asthma was graded from 1 to 4 according to the Aas scoring system. Twelve normal subjects were also studied as controls. Induction of sputum was performed by hypertonic saline to determine differential cell count, and eosinophil cationic protein (ECP) by the so-called "plug technique". The concentration of ECP was measured by a fluoroimmunoassay. Bronchial hyperresponsiveness was recorded by inhaling progressive concentrations of histamine, and the concentration that caused a 20% decrease in FEV1 (PC20) was calculated. Sputum eosinophils (range 0-61%), sputum ECP (range 24-10,800 microg x L[-1]) and serum ECP (range 4-61 microg x L[-1]) were significantly greater in asthmatics than in normal subjects, and distinguished the most severe group with the highest Aas score from the others. Sputum eosinophils and sputum ECP were strongly related to each other. The relationships between sputum or serum ECP and PC20 (range 0.016-7.5 mg x mL[-1]), and between sputum ECP and FEV1 were found to be weak. In conclusion, sputum outcomes of eosinophil activation and serum eosinophilic cationic protein appear to be useful indicators of disease. They do not accurately reflect current clinical or functional indices of asthma severity in chronic stable patients, and might therefore provide complementary data disease monitoring.
Prognostic value of serum fibronectin concentration in alcoholic cirrhotic patients
Authors: Sylvie Naveau, Thierry Poynard, Annie Abella, Jean-Pierre Pignon, Alain Poitrine, Hélène Agostini, Othar Zourabichvili, Jean-Claude Chaput
Journal: Hepatology (1985)

The aim of this study was to assess prospectively the prognostic value of serum fibronectin in 114 alcoholic cirrhotic patients and to compare serum fibronectin with other prognostic variables. The Cox model and log-rank test were used to compare survival rates at 1 year. Considered alone, serum fibronectin, age, serum albumin, total serum bilirubin, gamma-glutamyl transpeptidase, prothrombin time, presence of encephalopathy and ascites were associated with survival to 1 year. The estimated survival rate at the end of 1 year was, for patients with serum fibronectin greater than 165 mg per liter: 84 +/- 5%, and for patients with serum fibronectin less than or equal to 165 mg per liter: 53 +/- 7% (p less than 0.001). With the step-wise multidimensional analysis using the Cox model to assess the combined effect of several prognostic variables, serum fibronectin was the first variable selected followed by age, encephalopathy and serum albumin which entered the model by virtue of their independent prognostic value. Multivariate regression and partial correlation analysis showed that fibronectin was independently correlated with serum albumin, gamma-glutamyl transpeptidase and total serum bilirubin explaining that the prognostic value of albumin diminished and that the prognostic value of total serum bilirubin and gamma-glutamyl transpeptidase disappeared when combined with serum fibronectin.
Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes
Authors: N. Manjunath, P. Shankar, J. Wan, W. Weninger, M.A. Crowley, K. Hieshima, T.A. Springer, X. Fan, H. Shen, J. Lieberman, U.H. von Andrian
Journal: Journal of Clinical Investigation (2001)

The lineage relationship between short-lived effector T cells and long-lived memory cells is not fully understood. We have described T-GFP mice previously, in which naive and early activated T cells express GFP uniformly, whereas cells that have differentiated into effector cytotoxic T cells selectively lose GFP expression. Here we studied antigen-specific CD8 T cell differentiation using T-GFP mice crossed to the TCR transgenic (Tg) mice P14 (specific for the lymphocytic choriomeningitis virus glycoprotein peptide, gp33-41). After activation with antigenic peptide, P14XT-GFP CD8+ T cells cultured in high-dose IL-2 developed into cells with effector phenotype and function: they were blastoid, lost GFP expression, expressed high levels of activation and effector markers, and were capable of immediate cytotoxic function. In contrast, cells cultured in IL-15 or low-dose IL-2 never developed into full-fledged effector cells. Rather, they resembled memory cells: they were smaller, were GFP+, did not express effector markers, and were incapable of immediate cytotoxicity. However, they mediated rapid-recall responses in vitro. After adoptive transfer, they survived in vivo for at least 10 weeks and mounted a secondary immune response after antigen rechallenge that was as potent as endogenously generated memory cells. In addition to providing a simple means to generate memory cells in virtually unlimited numbers, our results suggest that effector differentiation is not a prerequisite for memory cell generation.
Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis
Authors: S.S. Lim, M.J. Davies, R.J. Norman, L.J. Moran
Journal: Human Reproduction Update (2012)

BACKGROUNDPolycystic ovary syndrome (PCOS) is closely associated with obesity but the prevalence of obesity varies between published studies. The objective of this research was to describe the prevalence of overweight, obesity and central obesity in women with and without PCOS and to assess the confounding effect of ethnicity, geographic regions and the diagnostic criteria of PCOS on the prevalence.
An Imageable Metastatic Treatment Model of Nasopharyngeal Carcinoma
Authors: Tengfei Liu, Yanqin Ding, Weibing Xie, Zuguo Li, Xiaoyan Bai, Xin Li, Weiyi Fang, Caiping Ren, Shuang Wang, Robert M. Hoffman, Kaitai Yao
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Nasopharyngeal carcinoma is highly prevalent in southern China and is often resistant to current treatment options. Experimental Design: Clinically relevant mouse models are necessary for further understanding and drug discovery in this disease. Two nasopharyngeal carcinoma cell lines, stably expressing green fluorescent protein (GFP), 5-8F-GFP and 6-10B-GFP, were established. The cells were orthotopically injected into the nasopharynx or ectopically into the subcutis of nude mice. Whole-body fluorescence imaging was used to monitor the growth of the primary tumor as well as angiogenesis and metastasis. Results: The metastatic behavior of 5-8F and 6-10B were distinct in the orthotopic model. Orthotopic implantation of highly metastatic 5-8F cells resulted in brain invasion, cervical lymph node metastases, and pulmonary metastases similar to what is often observed in patients. Cell line 6-10B was less metastatic, which occasionally resulted in pulmonary metastasis. GFP enabled imaging of micrometastasis. Neither 5-8F nor 6-10B were metastatic in the s.c. site. These results indicated that, in addition to the cancer cell type, the host microenvironment was critical for metastasis to occur consistent with the “seed-and-soil” hypothesis. 5-8F was highly sensitive to 5-fluorouracil (5-FU), whereas 6-10B was moderately sensitive. Conclusions: The imageable orthotopic model should play a critical role in elucidating the mechanisms involved in the growth, progression, metastasis, and angiogenesis of nasopharyngeal carcinoma and for evaluation of novel compounds with potential efficacy.
p53 and bcl-2 proteins as prognostic markers in human papillomavirus-associated cervical lesions.
Authors: K Kurvinen, K Syrjänen, S Syrjänen
Journal: Journal of Clinical Oncology (1996)

PURPOSE The present study was designed to analyze the expression of p53, mdm2, and bcl-2 proteins, with special emphasis on their association with the grade of squamous intraepithelial lesion (SIL), human papillomavirus (HPV) type, and clinical course of the disease. Special attention was focused on the value of individual protein expressions, as well as combined p53/mdm2 and p53/bcl-2 phenotypes, in predicting the clinical course of cervical lesions. MATERIALS AND METHODS The expression of p53, mdm2, and bcl-2 was studied immunohistochemically in a series of 98 HPV lesions of the uterine cervix. RESULTS Frequent expression of p53, mdm2, and bcl-2 proteins was found in the cervical lesions. However, only p53 expression independently provided information for prediction of the clinical course of HPV lesions. High levels of p53 expression were detected in most low-grade SILs (LSILs) (83%) and HPV 6/11/42-associated lesions (86%). In high-grade SILs (HSILs) positive for high-risk HPV types, p53 expression was frequently either totally absent or it only occurred in a few scattered cells. These lesions were closely associated with disease progression. The evaluation of bcl-2 expression alone was not useful for predicting clinical outcome, although abnormal bcl-2 expression in suprabasal layers was more common in HSILs. By contrast, the combined p53/bcl-2 phenotype, which showed a low percentage of p53-positive cells with bcl-2 overexpression in upper epithelial layers, was found to be involved in the progression of HPV lesions. CONCLUSION The present study showed that HPV lesions with a high percentage of cells that express p53 are more likely to regress than those with low or absent p53. p53 thus seems to hold promise as a molecular marker for the risk of the progression of HPV-associated SILs. In addition, the assessment of p53 and bcl-2 expression patterns may be useful to predict the clinical course of cervical HPV lesions.
What physical activity surveillance needs: validity of a single-item questionnaire
Authors: Miriam Wanner, Nicole Probst-Hensch, Susi Kriemler, Flurina Meier, Adrian Bauman, Brian W Martin
Journal: British Journal of Sports Medicine (2013)

Background Self-report instruments to assess physical activity are still the most feasible option in many population-wide surveys, and often need to be very short owing to resource constraints. The aim of this study was to test the criterion validity of a single-item physical activity measure using accelerometers and to compare its measurement properties by gender, age group (including older adults) and language region. Methods A validation study was carried out within the second follow-up of a large Swiss cohort study (Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults, SAPALDIA, n=208) and included an additional convenient sample (n=110). Participants wore an accelerometer over eight consecutive days and then completed the single-item measure. Spearman's rank-order correlations were used to assess the criterion validity. Results Physical activity levels were higher in men, younger individuals and those from the German-speaking part of Switzerland. Correlation coefficients for the number of days with at least 30 min of moderate-to-vigorous physical activity according to the single item and different accelerometer activity outcomes ranged from 0.40 to 0.54. Correlations were higher for women, younger individuals and participants from the French-speaking and the Italian-speaking parts. Conclusions The single-item physical activity measure performed at least as well as other physical activity questionnaires. The differences in criterion validity between sub groups indicate that factors such as gender and age should be taken into account when developing physical activity questionnaires and in future validation studies.
A gene-expression program reflecting the innate immune response of cultured intestinal epithelial cells to infection by Listeria monocytogenes
Authors: David N Baldwin, Veena Vanchinathan, Patrick O Brown, Julie A Theriot
Journal: Genome biology (2002)

Listeria monocytogenes is a Gram-positive, facultative, intracellular bacterial pathogen found in soil, which occasionally causes serious food-borne disease in humans. The outcome of an infection is dependent on the state of the infected individual's immune system, neutrophils being key players in clearing the microorganism from the body. The first line of host defense, however, is the intestinal epithelium. We have examined the transcriptional response of cultured human intestinal epithelial cells to infection by L. monocytogenes, which replicates in the host cell cytoplasm and spreads from cell to cell using a form of actin-based motility. We found that the predominant host response to infection was mediated by NFκB. To determine whether any host responses were due to recognition of specific virulence factors during infection, we also examined the transcriptional response to two bacterial mutants; actA which is defective in actin-based motility, and prfA, which is defective in the expression of all L. monocytogenes virulence genes. Remarkably, we found no detectable difference in the host transcriptional response to the wild-type and mutant bacteria. These results suggest that cultured intestinal epithelial cells are capable of mounting and recruiting a powerful innate immune response to L. monocytogenes infection. Our results imply that L. monocytogenes is not specifically detected in the host cytoplasm of Caco-2 cells by intracellular signals. This suggests that entry of bacteria is mediated in the host cell post-translationally, and that these bacteria seek the cytosol not only for the nutrient-rich environment, but also for protection from detection by the immune system.