tbuckley/cabot-search huggingface dataset:
POST-MORTEM HANDLING AND BRAIN BIOCHEMISTRY
Authors: M.L. Robinson, N.W.A. Marsh, E.D. Bird, E.G. Spokes, Joanna Barnes, A.V.P. Mackay, L.L. Iverson, Michael Shepherd, T.J. Crow, F. Owen, A.J. Cross, R. Lofthouse, A. Longden, M.H. Joseph, C.D. Frith
Journal: The Lancet (1978)
The measurement of the stratum corneum reservoir: a simple method to predict the influence of vehicles on in vivo percutaneous absorption
Authors: D. DUPUIS, A. ROUGIER, R. ROGUET, CLAIRE LOTTE
Journal: British Journal of Dermatology (1986)

The influence of nine vehicles on in vivo percutaneous absorption of benzoic acid has been studied in the hairless rat. Although the vehicles used were simple in composition, the total amount of benzoic acid which penetrated varied by a factor of 50. A weak relationship was found between penetration of benzoic acid and its maximum solubility in the different vehicles. A linear relationship was demonstrated between the amount of benzoic acid present in the stratum corneum at the end of a 30 min application period and the total amount absorbed over 4 days. We suggest that the influence of a vehicle on the overall absorption of a substance can therefore be predicted by simply measuring the amount present in the stratum corneum at the end of a 30 min application period.
Exercise training decreases store-operated Ca2+entry associated with metabolic syndrome and coronary atherosclerosis
Authors: J. M. Edwards, Z. P. Neeb, M. A. Alloosh, X. Long, I. N. Bratz, C. R. Peller, J. P. Byrd, S. Kumar, A. G. Obukhov, M. Sturek
Journal: Cardiovascular Research (2009)

Stenting attenuates restenosis, but accelerated coronary artery disease (CAD) adjacent to the stent (peri-stent CAD) remains a concern in metabolic syndrome (MetS). Smooth muscle cell proliferation, a major mechanism of CAD, is mediated partly by myoplasmic Ca2+ dysregulation and store-operated Ca2+ entry (SOCE) via canonical transient receptor potential 1 (TRPC1) channels is proposed to play a key role. Exercise is known to prevent Ca2+ dysregulation in CAD. We tested the hypothesis that MetS increases SOCE and peri-stent CAD and exercise attenuates these events. Groups (n = 9 pigs each) were (i) healthy lean Ossabaw swine fed standard chow, (ii) excess calorie atherogenic diet fed (MetS), and (iii) aerobically exercise trained starting after 50 weeks of development of MetS (XMetS). Bare metal stents were placed after 54 weeks on diets, and CAD and SOCE were assessed 4 weeks later. Coronary cells were dispersed proximal to the stent (peri-stent) and from non-stent segments, and fura-2 fluorescence was used to assess SOCE, which was verified by Ni2+ blockade and insensitivity to nifedipine. XMetS pigs had increased physical work capacity and decreased LDL/HDL (P < 0.05), but no attenuation of robust insulin resistance, glucose intolerance, hypertriglyceridaemia, or hypertension. CAD was greater in peri-stented vs. non-stented artery segments. MetS had the greatest CAD, SOCE, and TRPC1 and STIM1 mRNA and protein expression, which were all attenuated in XMetS. This is the first report of the protective effect of exercise on native CAD, peri-stent CAD, SOCE, and molecular expression of TRPC1, STIM1, and Orai1 in MetS.
Localization of protective epitopes of the amino terminus of type 5 streptococcal M protein.
Authors: J B Dale, E H Beachey
Journal: The Journal of Experimental Medicine (1986)

We have used a set of overlapping chemically synthesized peptides representing the amino terminus of type 5 streptococcal M protein to localize protective, as opposed to nonprotective and tissue-crossreactive epitopes that might be appropriate for vaccine formulations. Rabbit antisera raised against SM5(1-35) reacted in high titer with pep M5 by ELISA and opsonized type 5 streptococci. None of the antisera crossreacted with human heart tissue or myosin. Antisera against SM5(26-35) reacted with SM5(1-35) and pep M5 but failed to opsonize type 5 streptococci. Particle-phase ELISA indicated that SM5(26-35) antibodies were directed against nonprotective determinants of pep M5 that were not exposed on the surface of viable organisms. Opsonization and ELISA inhibition assays showed that, of the SM5(1-35) antibodies that reacted with M5, all were inhibited by SM5(14-35), whereas none was inhibited by SM5(26-35), suggesting that the protective epitopes of SM5(1-35) resided between residues 14 and 26. This was confirmed by subsequent chemical synthesis of this region; SM5(14-26) totally inhibited SM5(1-35) antibodies that reacted with pep M5 in ELISA, and completely inhibited opsonization of type 5 streptococci by SM5(1-35) antibodies. SM5(14-26) evoked high titers of type-specific, opsonic antibodies against type 5 streptococci, confirming the protective immunogenicity of this 13-residue peptide of type 5 M protein.
P172 Pulmonary Hypertension In Ipf: Utility Of Hrct
Authors: G. Bettini, M. Mazzei, D. Castria, E. Kacerja, R. Refini, F. De Negri, N. C. Squitieri, S. Guerrini, F. Mazzei, P. Rottoli, L. Volterrani
Journal: Thorax (2014)

<h3>Purpose</h3> To evaluate the reliability of HRCT-parameters suggesting Pulmonary Hipertension (PH) in a population of Idiopathic Pulmonary Fibrosis (IPF) patients with or without PH at right-sided-heart-catheterization. <h3>Methods and materials</h3> The HRCT scans of 26 patients with IPF, underwent both right-sided-heart-catheterization and echocardiography, were retrospectively, blindly and independently, evaluated by one radiology resident and one experienced-radiologist (with a 10-years-experience in thoracic-radiology). The diameter and area of Pulmonary Artery (PA), before its bifurcation, the diameter of ascending aorta and the mid anteroposterior-diameter of the thoracic vertebra, on the same CT-section, and the widest short-axis-diameters of four segmental arteries and bronchus, in both upper and lower lobes, were measured. The diameters of left ventricle and inferior vena cava, the presence of emphisema, pericardial effusion and hiatal hernia were also evaluated. <h3>Results</h3> 15 out of 29 patients had PH at RHC. The HRCT parameters related to the <i>mean pulmonary artery pressure</i> (mPAP) were: the PA-area (R<sup>2</sup>=0.238079; p = 0.04), the ratio of the PA-area to the ascending aorta diameter (R<sup>2</sup>=0.215345; p = 0.0524) and above all the ratio of the diameter of segmental artery to the adjacent bronchus in the left upper lobe (R<sup>2</sup>=0.354973; p = 0.0006). The combination of <i>systolic pulmonary artery pressure</i> (sPAP), the PA-area at HRCT and the ratio of the diameter of segmental artery to the adjacent bronchus in the apicoposterior segment of the left upper lobe was strongly correlated to mPAP (R<sup>2</sup>=0.785163; p = 0.0001). The contribution of other echocardiographic-parameters (longitudinal STRAIN and <i>Time-to-Peak STRAIN values</i>, TTP) in multivariate regression analysis was not statistically significant, probably because of the small number of patients. Using the ROC Analysis we found that 931,6 is the <i>upper limit of normal</i> (ULN) for the PA-area, with a 86% sensitivity and 61% specificity (0.839 AUC); while 20.34 is the ULN for the ratio of the PA-area to the ascending aorta diameter, with a 100% sensitivity and 50% specificity (0.804 AUC). <h3>Conclusion (S)</h3> HRCT remains an useful tool to identify patients with PH, however the combination of HRCT and echocardiograpy improves accuracy in PH diagnosis.
Origin of Murine B Cell Lineages
Authors: A B Kantor, L A Herzenberg
Journal: Annual Review of Immunology (1993)

Until recently, the hematopoietic stem cells (HSC) that appear early in ontogeny were thought to constitute a homogeneous, self-replenishing population whose developmental potential remains constant throughout the life of the animal. Studies reviewed here, however, demonstrated clear differences in the developmental potential of fetal and adult progenitor populations (including FACS-sorted HSC). These studies, which chart the ability of various progenitor sources to reconstitute functionally distinct B cell populations, define three B cell lineages: B-1a cells (CD5 B cells), derived from progenitors that are present in fetal omentum and fetal liver but are largely absent from adult bone marrow; B-1b cells ("sister" population), derived from progenitors that are present in fetal omentum, fetal liver, and also in adult bone marrow; and conventional B cells, whose progenitors are missing from fetal omentum but are found in fetal liver and adult bone marrow. B-1a and B-1b cells share many properties, including self-replenishment and feedback regulation of development. These B cell studies, in conjunction with evidence for a similar developmental switch for T cells and erythrocytes, suggest that evolution has created a "layered" immune system in which successive progenitors (HSC) reach predominance during development and give rise to differentiated cells (B, T, etc) responsible for progressively more complex immune functions.
Minimally important difference in diffuse systemic sclerosis: results from the D-penicillamine study
Authors: Dinesh Khanna, Daniel E. Furst, Ron D. Hays, Grace S. Park, Weng Kee Wong, James R. Seibold, Maureen D. Mayes, Barbara White, Fredrick F. Wigley, Michael Weisman, Walter Barr, Larry W. Moreland, Thomas A. Medsger, Virginia D. Steen, Richard W. Martin, David H. Collier, Arthur Weinstein, Edward Lally, John Varga, Steven R Weiner, Brian Andrews, Micha Abeles, Philip J. Clements
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To estimate minimally important differences (MIDs) in scores for the modified Rodnan Skin Score (mRSS) and Health Assessment Questionnaire—Disability Index (HAQ-DI) in a clinical trial on diffuse systemic sclerosis (SSc). <b>Participants and methods:</b> 134 people participated in a 2-year, double-blind, randomised clinical trial comparing efficacy of low-dose and high-dose d-penicillamine in diffuse SSc. At 6, 12, 18 and 24 months, the investigator was asked to rate the change in the patient's health since entering the study: markedly worsened, moderately worsened, slightly worsened, unchanged, slightly improved, moderately improved or markedly improved. Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved. <b>Results:</b> The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 (0.40–0.66 effect size) and for the HAQ-DI from 0.10 to 0.14 (0.15–0.21 effect size). Patients who were rated to improve more than slightly were found to improve by 6.9–14.2 (0.86–1.77 effect size) on the mRSS and 0.21–0.55 (0.32–0.83 effect size) on the HAQ-DI score. <b>Conclusion:</b> MID estimates are provided for improvement in the mRSS and HAQ-DI scores, which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc.
Fibrinolytic Therapy in Mechanical Valve Thrombosis in a One-Year-Old Girl
Authors: Ting-An Yen, Yih-Sharng Chen, Chun-An Chen, Ching-Chia Wang, Chung-I Chang, En-Ting Wu, Ming-Tai Lin, Jou-Kou Wang, Mei-Hwan Wu, Shuenn-Nan Chiu
Journal: Circulation (2010)
microRNA-146a inhibits cancer metastasis by downregulating VEGF through dual pathways in hepatocellular carcinoma
Authors: Zheng Zhang, Yang Zhang, Xiu-Xuan Sun, Xi Ma, Zhi-Nan Chen
Journal: Molecular Cancer (2015)

Growing evidence indicates that miR-146a is involved in carcinogenesis and tumor progression in several human malignancies. However, the molecular details underlying miR-146a mediated regulation of its target genes and its precise biological function in cancer, especially in hepatocellular carcinoma (HCC) remains unclear. The expression levels of genes including miR-146a, APC, VEGF and HAb18G were examined in HCC cell lines and patient specimens were compared with control levels using quantitative reverse transcription-PCR. The functions of miR-146a and HAb18G in migration/invasion and liver metastasis formation were determined by transwell and spleen injection assays, respectively. miR-146a related genes were determined by PCR array. The potential regulatory targets of miR-146a were determined by bioinformatics and prediction tools, correlation with target protein expression, and luciferase reporter assay. DNA methylation status of miR-146a promoter were performed by PCR analysis of bisulfite-modified genomic DNA. We demonstrated that miR-146a expression was markedly downregulated in hepatoma cells and hepatoma tissues compared to immortalized normal liver epithelial cells and normal hepatic tissues. DNA methylation of miR-146a promoter correlated with its downexpression and with liver cancer metastasis. The restoration of miR-146a dramatically suppressed HCC cell invasion and metastasis by repressing VEGF expression through upregulating APC, which inhibits β-catenin accumulation in nucleus, and downregulating NF-κB p65 by targeting HAb18G. In human HCC, miR-146a expression was negative correlated with increased HAb18G, VEGF, NF-κB p65 and beneficial prognosis. This study identified a novel target of miR-146a and defined miR-146a as a crucial tumor suppressor in human HCC that acts through multiple pathways and mechanisms to suppress HCC invasion or metastasis.
Late Effects of Cancer and Hematopoietic Stem-Cell Transplantation on Spouses or Partners Compared With Survivors and Survivor-Matched Controls
Authors: Michelle M. Bishop, Jennifer L. Beaumont, Elizabeth A. Hahn, David Cella, Michael A. Andrykowski, Marianne J. Brady, Mary M. Horowitz, Kathleen A. Sobocinski, J. Douglas Rizzo, John R. Wingard
Journal: Journal of Clinical Oncology (2007)

Purpose Little is known about the long-term effects of cancer and hematopoietic stem-cell transplantation (HCT) on spouses or partners. The purpose of this study was to examine the health-related quality of life and post-traumatic growth (PTG) of spouses/partners compared with survivors and controls and to identify factors associated with those outcomes. Patients and Methods HCT survivor/partner pairs (n = 177), coupled continuously since HCT, were drawn from 40 North American transplantation centers. Married peer-nominated acquaintances (of survivors) served as controls (n = 133). Outcomes were measured a mean of 6.7 years after HCT (range, 1.9 to 19.4 years). Results As expected, self-reported partner physical health was similar to controls and better than survivors (P &lt; .001). However, partners reported more fatigue and cognitive dysfunction than controls (P &lt; .001 for both), although less than survivors. Partners and survivors reported more depressive symptoms and sleep and sexual problems than controls (P &lt; .001, P &lt; .01, and P &lt; .01, respectively). Odds of partner depression were nearly 3.5 times that of controls (P &lt; .002). Depressed partners were less likely than depressed survivors to receive mental health treatment (P &lt; .04). Partners reported less social support (P &lt; .001), dyadic satisfaction (P &lt; .05), and spiritual well-being (P &lt; .05) and more loneliness (P &lt; .05) than both survivors and controls. In contrast to survivors, partners reported little PTG (P &lt; .001). Factors associated with partner outcomes included partner health problems, coping, female sex, social constraint, survivor depression, optimism, multiple life changes, and social support. Conclusion Spouses/partners experience similar emotional and greater social long-term costs of cancer and HCT than survivors without the potential compensatory benefits of PTG. Some of the factors associated with partner outcomes are amenable to intervention.
Results of a Multicenter Prospective Study on the Postoperative Treatment of Unilateral Retinoblastoma After Primary Enucleation
Authors: Isabelle Aerts, Xavier Sastre-Garau, Alexia Savignoni, Livia Lumbroso-Le Rouic, Estelle Thebaud-Leculée, Didier Frappaz, Carole Coze, Caroline Thomas, Marion Gauthier-Villars, Christine Lévy-Gabriel, Hervé J. Brisse, Laurence Desjardins, François Doz
Journal: Journal of Clinical Oncology (2013)

Purpose The objective of this prospective study was to assess overall survival and event-free survival in patients with intraocular unilateral retinoblastoma (Reese-Ellsworth group V) treated by primary enucleation with or without adjuvant therapy depending on histopathologic risk factors. Patients and Methods Patients (n = 123) were divided into three groups on the basis of risk factors for extraocular relapse and metastasis assessed on centralized histologic examination of enucleated eyes. Group 1 (n = 70) had minimal or no choroidal involvement and/or prelaminar or no optic nerve involvement and received no adjuvant therapy. Group 2 (n = 52) had massive choroidal involvement and/or intra- or retrolaminar optic nerve involvement and/or anterior segment involvement and received four courses of adjuvant chemotherapy. Group 3 (n = 1) had invasion of the surgical margin of the optic nerve and/or microscopic extrascleral involvement and received six courses of adjuvant chemotherapy with intrathecal thiotepa, consolidation chemotherapy, and autologous stem-cell rescue. Genetic testing was also performed. Results Median follow-up for the 123 patients was 71 months. No disease progression, relapse, or distant metastasis occurred during follow-up. No second malignancies occurred. This requires confirmation with longer follow-up. Secondary bilateralization occurred in two patients with identified RB1 germline mutation. Adjuvant chemotherapy was well tolerated, with limited toxicity. Molecular testing found constitutional RB1 gene mutations in only nine of 100 evaluated patients. Conclusion The survival rate of 100% was excellent, including 57% of patients who received no adjuvant therapy, suggesting that chemotherapy could be de-escalated in some patients, especially those with massive choroidal involvement.
Direct Inhibition of Expressed Cardiac L-Type Ca <sup>2+</sup> Channels by <i>S</i> -Nitrosothiol Nitric Oxide Donors
Authors: Hai Hu Nipavan Chiamvimonvat Toshio Yamagishi Eduardo Marban
Journal: Circulation Research (1997)

Abstract NO donors have complex effects on Ca 2+ currents in native cardiac cells, with reports of direct stimulation and indirect cGMP-mediated inhibition or stimulation. To investigate the molecular basis of these effects, we tested the effects of one class of NO donors, S -nitrosothiols (RSNOs), on expressed cardiovascular L-type Ca 2+ channels (α 1C ±β 1a ±α 2 or α 1C ±β 2a ±α 2 ) in human embryonic kidney (HEK293) cells. The RSNO compounds we used were S -nitroso- N -acetylpenicillamine (SNAP, 5 to 10 nmol/L or 100 to 800 μmol/L), S -nitrosocysteine (SNC, 100 μmol/L or 1 mmol/L), and S -nitrosoglutathione (GSNO, 1 mmol/L). Currents were measured using whole-cell patch recordings with 2 to 10 mmol/L Ba 2+ as the charge carrier. SNAP reduced the amplitude of barium currents (I Ba ) through all the subunit combinations, with an EC 50 of 360 μmol/L for α 1C +β 1a channels. SNC or GSNO also inhibited I Ba , albeit less potently. The inhibitory effect of SNAP was not affected by methylene blue (10 to 30 μmol/L) or 8-bromo-cGMP (200 to 400 μmol/L). The effects are relatively specific for Ca 2+ channels, as expressed cardiac or skeletal muscle Na + channels, which have a similar overall architecture, were barely affected by SNAP at concentrations as high as 1 mmol/L. We conclude that in the HEK293 expression system, the S -nitrosothiol NO donors inhibit L-type Ca 2+ channels by a mechanism independent of cGMP.
Chronic ethanol consumption increases the fragility of rat pancreatic zymogen granules.
Authors: P S Haber, J S Wilson, M V Apte, M A Korsten, R C Pirola
Journal: Gut (1994)

Intracellular activation of pancreatic digestive enzymes by lysosomal hydrolases is thought to be an early event in the pathogenesis of pancreatic injury. As ethanol excess is an important association of pancreatitis, experimental work has been directed towards exploring possible mechanisms whereby ethanol may facilitate contact between inactive digestive enzyme precursors and lysosomal enzymes. The aim of this study was to find out if chronic ethanol administration increases the fragility of rat pancreatic zymogen granules. Sixteen male Sprague-Dawley rats were pair fed ethanol and control liquid diets for four weeks. Zymogen granule fragility was then assessed in pancreatic homogenate by determination of (a) latency and (b) per cent supernatant enzyme after sedimentation of zymogen granules. Amylase was used as a zymogen granule marker enzyme. Latency was significantly reduced in pancreatic homogenates of ethanol fed animals suggesting increased zymogen granule fragility. In support of this finding, there was a trend towards increased supernatant enzyme after ethanol feeding. In conclusion, administration of ethanol increases the fragility of pancreatic zymogen granules in the absence of morphological evidence of pancreatic injury. It is proposed that zymogen granule fragility may play an early part in the pathogenesis of alcoholic pancreatitis by permitting contact between digestive and lysosomal enzymes.
Serum immunoglobulins and immunoglobulin G subclasses in cystic fibrosis related to the clinical state of the patient
Authors: ME Hodson, L Morris, JC Batten
Journal: European Respiratory Journal (1988)

Levels of serum immunoglobulins and immunoglobulin G subclasses were measured in 32 cystic fibrosis (CF) patients, 30 asthmatics and 27 controls. When compared with the asthmatic patients and controls, the CF patients had raised levels of all IgG subclasses as well as total IgG, IgM and IgA, but there was not a statistically significant increase in IgE. The levels of immunoglobulins in the CF patients were examined in relation to the clinical features of the disease. Raised levels of IgG4 were related to levels of IgE, but these raised levels of IgG4 appeared to be part of a general increase in total IgG and not an isolated feature. There was a significant correlation between the total IgG level and its subclasses, IgG1, IgG2, IgG3, IgG4 and IgA. IgG1 was significantly correlated with IgG2 and IgG4; IgG2 with IgG4; and IgG4 with IgE. Total IgG was the immunoglobulin most closely correlated with poor lung function. Serum IgA was higher in patients with positive immediate skin prick reactions to pollens (p less than 0.005) and death within two years of the study was related to high levels of total IgG (p less than 0.01), IgG3 (p less than 0.001), IgA (p less than 0.001), and IgE (p less than 0.005).
Final Efficacy and Safety Analysis of the Carin Phase III Trial: Capecitabine (Cap) and Bevacizumab (Bev) with or Without Vinorelbine (Vin) in 1St Line Metastatic Breast Cancer (Mbc)
Authors: A. Welt, N. Marschner, C. Lerchenmüller, T. Decker, C. Salat, S. Busies, S. Hegewisch-Becker
Journal: Annals of Oncology (2014)