tbuckley/cabot-search huggingface dataset:
Gene Delivery in Renal Tubular Epithelial Cells Using Recombinant Adeno-Associated Viral Vectors
Authors: Sifeng Chen, Anupam Agarwal, Olena Y. Glushakova, Marda S. Jorgensen, Shashikumar K. Salgar, Amy Poirier, Terence R. Flotte, Byron P. Croker, Kirsten M. Madsen, Mark A. Atkinson, William W. Hauswirth, Kenneth I. Berns, C. Craig Tisher
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Gene therapy has the potential to provide a therapeutic strategy for numerous renal diseases such as diabetic nephropathy, chronic rejection, Alport syndrome, polycystic kidney disease, and inherited tubular disorders. In previous studies using cationic liposomes or adenoviral or retroviral vectors to deliver genes into the kidney, transgene expression has been transient and often associated with adverse host immune responses, particularly with the use of adenoviral vectors. The unique properties of recombinant adeno-associated viral (rAAV) vectors permit long-term stable transgene expression with a relatively low host immune response. The purpose of the present study was to evaluate gene expression in the rat kidney after intrarenal arterial infusion of a rAAV (serotype 2) vector encoding green fluorescence protein (GFP) induced by a cytomegalovirus-chicken beta-actin hybrid promoter. The left kidney of experimental animals was treated with either saline or transduced with rAAV2-GFP (0.125 ml/100 g body wt, 1 × 1010/ml infectious units) through the renal artery. A time-dependent expression of GFP was observed in all kidneys injected with rAAV2-GFP, with maximal expression observed at 6 wk posttransduction. The expression of GFP was restricted to cells in the S3 segment of the proximal tubule and intercalated cells in the collecting duct, the latter identified by co-localization with H+-ATPase. No transduction was observed in the glomeruli or the intrarenal vasculature. These studies demonstrate successful transgene expression in tubular epithelial cells, specifically in the S3 segment of the proximal tubule and intercalated cells, after intrarenal administration of a rAAV vector and provide the impetus for further studies to exploit its use as a tool for gene therapy in the kidney. E-mail: [email protected]
Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON)
Authors: Leo F. Verdonck, Annelise Notenboom, Daphne D. de Jong, Marius A. MacKenzie, Gregor E. G. Verhoef, Mark H. H. Kramer, Gert J. Ossenkoppele, Jeanette K. Doorduijn, Pieter Sonneveld, Gustaaf W. van Imhoff
Journal: Blood (2006)
Vitronectin enhances internalization of crocidolite asbestos by rabbit pleural mesothelial cells via the integrin alpha v beta 5.
Authors: A M Boylan, D A Sanan, D Sheppard, V C Broaddus
Journal: Journal of Clinical Investigation (1995)

The mechanism by which pleural mesothelial cells, the likely progenitor cells of asbestos-induced mesothelioma, recognize and internalize crocidolite asbestos is unknown. Because incubation of asbestos fibers with serum increases their association with cells, we asked whether a protein coat on asbestos increased internalization of fibers via specific cellular receptors. Coating crocidolite with citronectin, but not with fibronectin or other proteins, increased fiber internalization by rabbit pleural mesothelial cells, as measured by a new technique using fluorescence confocal microscopy. Receptors for vitronectin, alpha v beta 3 and alpha v beta 5, were identified on mesothelial cells. Inhibiting vitronectin receptors by plating cells on a vitronectin substrate or incubating cells with excess soluble vitronectin reduced internalization of vitronectin-coated crocidolite. Inhibition of alpha v beta 5, but not alpha v beta 3, with blocking antibodies similarly reduced internalization. In addition, alpha v beta 5, but not alpha v beta 3, showed immunocytochemical colocalization with fibers. Of biologic relevance, coating crocidolite with serum also increased internalization via alpha v beta 5, an effect dependent on the vitronectin in serum. We conclude that pleural mesothelial cells recognize and internalize vitronectin- and serum-coated asbestos via the integrin alpha v beta 5. Since integrins initiate some of the same signaling pathways as does asbestos, our findings may provide insights into the mechanisms of asbestos-induced biologic effects.
Assessment of Myocardial Viability With Contrast-Enhanced Magnetic Resonance Imaging
Authors: Christoph Klein, Stephan G. Nekolla, Frank M. Bengel, Mitsuru Momose, Andrea Sammer, Felix Haas, Bernhard Schnackenburg, Wolfram Delius, Harald Mudra, Dieter Wolfram, Markus Schwaiger
Journal: Circulation (2002)

Background — Recent studies indicate that MRI, after administration of gadolinium-diethylenetriamine pentaacetic acid, can identify nonviable areas in dysfunctional myocardium. We compared MRI hyperenhancement with PET as a gold standard for detection and quantification of myocardial scar tissue. Methods and Results — Thirty-one patients with ischemic heart failure (ejection fraction, 28±9%) were imaged with PET and MRI. Scar was defined as regionally increased MRI signal intensity 20 minutes after injection of 0.2 mmol/kg gadolinium-diethylenetriamine pentaacetic acid and as concordantly reduced perfusion and glucose metabolism as defined by PET. Sensitivity and specificity of MRI in identifying patients and segments (n=1023) with matched flow/metabolism defects was 0.96 of 1.0 and 0.86 of 0.94, respectively. Eleven percent of segments defined as viable by PET showed some degree of MRI hyperenhancement. Defect severity score based on visual analysis was 44.3±9.1 for PET and 47.6±11.1 for MRI ( r =0.91, P &lt;0.0001). Quantitatively assessed relative MRI infarct mass correlated well with PET infarct size ( r =0.81, P &lt;0.0001). Furthermore, MRI hyperenhancement was a better predictor of scar tissue than end-diastolic and end-systolic wall thickness or thickening. Conclusions — In severe ischemic heart failure, MRI hyperenhancement as a marker of myocardial scar closely agrees with PET data. Although hyperenhancement correlated with areas of decreased flow and metabolism, it seems to identify scar tissue more frequently than PET, reflecting the higher spatial resolution. Additional functional studies after revascularization are required to define the significance of small islands of scar detected by MRI.
The Effect of Digital Rectal Examination on Prostate-Specific Antigen Levels
Authors: E D Crawford, M J Schutz, S Clejan, J Drago, M I Resnick, G W Chodak, L G Gomella, M Austenfeld, N N Stone, B J Miles
Journal: JAMA (1992)

OBJECTIVE--To identify the effect of digital rectal examination (DRE) on serum prostate-specific antigen (PSA) levels. DESIGN--A prospective trial before and after DRE. SETTING--Multicenter outpatient screening program. PATIENTS--A total of 2754 healthy men aged 40 years and older who presented to a prostate cancer screening program and consented to two phlebotomies. MAIN OUTCOME MEASURE--Changes in serum PSA levels after DRE. RESULTS--Patients were divided into four groups based on their initial serum PSA levels. The levels were chosen based on previous studies that showed different incidences of prostate cancer within these groups. The two groups with the lowest initial PSA values (0.1 through 4 micrograms/L and 4.1 through 10 micrograms/L) were found to have statistically insignificant changes in the serum PSA levels after DRE. The group with initial PSA levels of 10.1 through 20 micrograms/L had increases in serum PSA values that showed a trend toward statistical significance. The group with initial PSA levels of greater than 20 micrograms/L had statistically significant increases in serum PSA values after DRE. The alterations in serum PSA levels in the two groups with the highest PSA values were not clinically important as the patients' clinical treatment was not altered. CONCLUSIONS--No clinically important effects on serum PSA levels were noted after DRE.
Electrogastrographic study of gastric myoelectrical activity in patients with unexplained nausea and vomiting.
Authors: H Geldof, E J van der Schee, M van Blankenstein, J L Grashuis
Journal: Gut (1986)

Using cutaneous electrodes an electrogastrographic study was made of gastric myoelectrical activity in both the fasting and postprandial states in 48 patients with unexplained nausea and vomiting and in 52 control subjects. A gastric emptying study, using a radio-labelled solid phase meal, was carried out in 30 of these 48 patients. A follow up study was done after one year. In 48% of the patients abnormal myoelectrical activity was found which was characterised by: instability of the gastric pacemaker frequency; tachygastrias in both the fasting and postprandial states; the absence of the normal amplitude increase in the postprandial electrogastrogram. This last characteristic was correlated with a delayed gastric emptying of solids. The present study shows that with electrogastrography in a heterogeneous group of patients with unexplained nausea and vomiting a subgroup can be discerned with abnormal myoelectrical activity. Our findings suggests that this abnormal myoelectrical activity is related to these symptoms.
Football medicine, revised edn
Authors: K Khan
Journal: British Journal of Sports Medicine (2006)

Edited by Jan Ekstrand, Jon Karlsson, Alan Hodson. Published by Taylor & Francis, 2003, £32.50, hardcover, pp 562. ISBN 1841841641

What is the difference between a well intentioned, but, in truth, mediocre manual and a treasured tome of great utility to the reader? Is it too sweeping to suggest that the premier book is ( a ) correct, ( b ) clear, ( c ) concise, ( d ) contemporary, ( e ) carefully constructed, ( f ) clinically relevant, and ( g ) copiously illustrated in colour?

Sweden’s frontline of soccer/football doctors, Jan Ekstrand and Jon Karlsson, together with …
Basolateral membrane H/OH/HCO3 transport in the rat cortical thick ascending limb. Evidence for an electrogenic Na/HCO3 cotransporter in parallel with a Na/H antiporter.
Authors: R Krapf
Journal: Journal of Clinical Investigation (1988)

Mechanisms involved in basolateral H/OH/HCO3 transport in the in vitro microperfused rat cortical thick ascending limb were examined by the microfluorometric determination of cell pH using (2',7')-bis-(carboxyethyl)-(5,6)-carboxyfluorescein. The mean cell pH in this segment perfused with 147 mM sodium and 25 mM HCO3 at pH 7.4 was 7.13 +/- 0.02 (n = 30). Lowering bath HCO3 from 25 to 5 mM (constant PCO2 of 40 mmHg) acidified the cells by 0.31 +/- 0.02 pH units at a rate of 0.56 +/- 0.08 pH units/min. Removal of bath sodium acidified the cells by 0.28 +/- 0.03 pH units at a rate of 0.33 +/- 0.04 pH units/min. The cell acidification was stilbene inhibitable and independent of chloride. There was no effect of bath sodium removal on cell pH in the absence of CO2/HCO3. Depolarization of the basolateral membrane (step increase in bath potassium) independent of the presence of chloride. Cell acidification induced by bath sodium removal persisted when the basolateral membrane was voltage clamped by high potassium/valinomycin. Although these results are consistent with a Na/(HCO3)n greater than 1 cotransporter, a Na/H antiporter was also suggested: 1 mM bath amiloride inhibited the cell pH defense against an acid load (rapid ammonia washout), both in the presence and absence of CO2/HCO3, and inhibited the cell acidification induced by bath sodium reduction from 50 to 0 mM. In conclusion, an electrogenic Na/(HCO3)n greater than 1 cotransporter in parallel with a Na/H antiporter exist on the basolateral membrane of the rat cortical thick ascending limb.
Six-minute walk test in children with chronic conditions
Authors: J Hassan, J van der Net, P J M Helders, B J Prakken, T Takken
Journal: British Journal of Sports Medicine (2008)

The 6-minute walk test (6MWT) is a frequently used indicator of functional exercise capacity. The goals of this study were to compare the 6-minute walk performance of three paediatric patient groups with that of healthy peers, to assess differences between published reference values and to investigate which anthropometric characteristics best predict 6-minute walk performance.47 children with haemophilia (mean (SD) age 12.5 (2.9) years), 44 with juvenile idiopathic arthritis (JIA) (mean age 9.3 (2.2) years) and 22 with spina bifida (SB) (mean age 10.3 (3.1) years) were included. Subjects performed a 6MWT, and the distance walked (6MWD) was compared with published reference values.The haemophilia, JIA and SB patients achieved 90%-92%, 72%-75% and 60%-62% of predicted walking distances, respectively. There were significant associations between 6MWD and age, height and weight in the haemophilia group and 6MWD and height in the JIA group. None of the anthropometric variables was significantly related to 6MWD in the SB group. All anthropometric variables were strongly correlated with walking distance-body weight product (6Mwork) in all groups. Height explained 24% (haemophilia) and 11% (JIA) of the variance in 6MWD and 84% (haemophilia), 78% (JIA) and 73% (SB) of the variance in 6Mwork.Walking distances of children with haemophilia, JIA and SB are significantly reduced compared with healthy references. Walking distance-body weight product seems to be a better outcome measure of the 6MWT compared with distance walked alone. Height is the best predictor of 6MWD and 6Mwork.
Bronchial responsiveness to distilled water and methacholine and its relationship to inflammation and remodeling of the airways in asthma.
Authors: A Chetta, A Foresi, M Del Donno, G F Consigli, G Bertorelli, A Pesci, R A Barbee, D Olivieri
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Although bronchial hyperresponsiveness in asthma is associated with inflammation within the airways, it is not known whether the degree and type of inflammation influence the response to different stimuli and whether pathologic changes of airway structure influence the bronchoconstrictive responses. Therefore, number of inflammatory cells in the epithelium and the lamina propria and the basement membrane thickness were estimated from bronchial biopsies taken in 27 asthmatic subjects (range percent predicted FEV1: 75.6 to 132.1, range of daily PEF variability: 1.9% to 20%) and related to the degree of bronchial responsiveness to ultrasonically nebulized distilled water (UNDW) and methacholine (M). PD20UNDW (provocative dose) was measurable in 15 of 27 patients and ranged between 1.01 and 20.4 ml. PC20M (provocative concentration) ranged between 0.15 and 31.7 mg/ml. In the 15 responders to UNDW, total inflammatory cells (p<0.04) and eosinophils (p<0.015) within the epithelium were higher than in 12 nonresponders to UNDW (PD20 > 34.8 ml). There was no correlation between PD20UNDW and any cell counts whereas negative correlations were found between PC20M and both total inflammatory cells (rs = -0.57; p<0.005) and eosinophils (rs = -0.63; p< 0.0015) within the epithelium. The degree of thickening of subepithelial layer ranged between 7 and 16 micrometers+ (n=26). Thickness correlates both with total inflammatory cells (rs = 0.49; p<0.025) and eosinophils (rs = 0.61; p< 0.003) within the epithelium. Moreover, it was correlated with baseline FEV1 (rs = -0.57; p<0.003) and daily peak expiratory flow (PEF) variability (rs = 0.51; p<0.01). A weak but significant correlation was also found between subepithelial layer thickness and PC20M (rs = -0.42; p<0.04). The results of this study demonstrate that eosinophilic inflammation of bronchial epithelium plays a role in determining UNDW and M responsiveness in asthma. Moreover, they suggest that remodeling of the airways such as thickening of subepithelial layer correlates with indices of asthma severity and could contribute to the degree of M but not to UNDW responsiveness.
The 2 receptor and airway hyper-responsiveness: are sensory nerves involved?
Authors: C. Page
Journal: Thorax (2009)

The use of β2 agonists for the control of symptoms is central to the treatment of patients with asthma. However, there is controversy surrounding the regular use of this drug class as numerous studies have demonstrated a variety of changes that can be considered unwanted attributes, particularly when these drugs are used regularly as monotherapy. These include increased bronchial hyper-responsiveness (BHR) to inhaled contractile agents1 and an increase in the allergen-induced early2 and late asthmatic response3 following regular treatment with short-acting β2 agonists (SABAs). Furthermore, a number of studies have suggested that regular treatment with inhaled SABAs and long-acting β2 agonists (LABAs) by inhalation leads to a loss of bronchoprotection4 5 and with salmeterol treatment an excess mortality in patients with asthma,6 a trend also observed with regular treatment with formoterol.7 This has led the Food and Drug Administration (FDA) to post black-box warnings on all medicines containing these LABAs.

Christian Virchow and colleagues from Rostock have provided data ( see page 763 ) on a potential mechanism as to how regular treatment with salmeterol can paradoxically increase BHR. …
Halothane hepatitis in children.
Authors: J G Kenna, J Neuberger, G Mieli-Vergani, A P Mowat, R Williams
Journal: BMJ (1987)

It is often stated that halothane hepatitis in children is nonexistent or extremely rare. This syndrome occurred in seven children aged between 11 months and 15 years, one of whom, a 3 1/2 year old boy, died with fulminant hepatic failure. All the children had received multiple halothane anaesthetics (range 2-6, median 3). In all cases other causes of liver diseases were excluded, and in all but one the diagnosis was confirmed serologically by antibodies to halothane altered liver cell membrane antigens. These findings suggest that halothane hepatitis occurs in children, and the risk of halothane hepatitis should therefore be considered when choosing which agents to use in children who require multiple anaesthetics.
Association of Glucocorticoid Insensitivity with Increased Expression of Glucocorticoid Receptor β
Authors: Donald Y.M. Leung, Qutayba Hamid, Alessandra Vottero, Stanley J. Szefler, Wendy Surs, Eleanor Minshall, George P. Chrousos, Dwight J. Klemm
Journal: The Journal of Experimental Medicine (1997)

In many chronic inflammatory disorders, glucocorticoid (GC) insensitivity is a challenging clinical problem associated with life-threatening disease progression. The molecular basis of GC insensitivity, however, is unknown. Alternative splicing of the GC receptor (R) pre-messenger RNA generates a second GCR, termed GCR-beta, which does not bind GCs but antagonizes the transactivating activity of the classic GCR, termed GCR-alpha. In the current study, we demonstrate that GC-insensitive asthma is associated with a significantly higher number of GCR-beta-immunoreactive cells in peripheral blood than GC-sensitive asthmatics or normal controls. Furthermore, we show that patients with GC-insensitive asthma have cytokine-induced abnormalities in the DNA binding capability of the GCR. These abnormalities can be reproduced by transfection of cell lines with the GCR-beta gene resulting in significant reduction of their GCR-alpha DNA binding capacity. We conclude that increased expression of GCR-beta is cytokine inducible and may account for GC insensitivity in this common inflammatory condition.
Limited joint mobility in diabetes mellitus.
Authors: R R Campbell, S J Hawkins, P J Maddison, J P Reckless
Journal: Annals of the Rheumatic Diseases (1985)

The relationship of limited joint mobility and finger joint contractures in diabetics to age of onset, duration, and control of diabetes has not been established. We measured the mobility of metacarpophalangeal, wrist, elbow, and ankle joints and assessed the prevalence of finger joint contractures in 254 young diabetics and 110 controls. The presence of microvascular disease was assessed by ophthalmoscopy and urine analysis for proteinuria. An estimate of long-term diabetic control was obtained from a postal questionnaire. A generalised reduction in joint mobility was present in diabetics of all ages two years after diagnosis. The reduction in joint mobility in controls between the ages of 12 and 13 was exaggerated in the diabetics. Diabetics diagnosed before puberty were more severely affected than those with a postpubertal onset, independent of duration of diabetes. Finger joint contractures were a significant feature of longstanding diabetics (nine years or more duration) only.
T <sup>−786</sup> →C Mutation in the 5′-Flanking Region of the Endothelial Nitric Oxide Synthase Gene Is Associated With Coronary Spasm
Authors: Masafumi Nakayama, Hirofumi Yasue, Michihiro Yoshimura, Yukio Shimasaki, Kiyotaka Kugiyama, Hisao Ogawa, Takeshi Motoyama, Yoshihiko Saito, Yoshihiro Ogawa, Yoshihiro Miyamoto, Kazuwa Nakao
Journal: Circulation (1999)

Coronary spasm plays an important role in the pathogenesis of ischemic heart diseases in general. However, the precise mechanism(s) responsible for coronary spasm remains to be elucidated, and we examined the molecular genetics of coronary spasm.We searched for the possible mutations in the endothelial nitric oxide synthase (eNOS) gene in patients with coronary spasm. In this study, we demonstrate the existence of 3 linked mutations in the 5'-flanking region of the eNOS gene (T-786-->C, A-922-->G, and T-1468-->A). The incidence of the mutations was significantly greater in patients with coronary spasm than in the control group (P<0.0001). Multiple logistic regression analysis with forward stepwise selection using the environmental risk factors and the eNOS gene variant revealed that the most predictive independent risk factor for coronary spasm was the mutant allele (P<0.0001). As assessed by luciferase reporter gene assays, the T-786-->C mutation resulted in a significant reduction in eNOS gene promoter activity (P<0.05), whereas neither the A-922-->G nor the T-1468-->A mutation had any affect.Taken together, these findings strongly suggest that the T-786-->C mutation in the eNOS gene reduces the endothelial NO synthesis and predisposes the patients with the mutation to coronary spasm.
Age Group–Specific Gap Between Treatment Cost of and Mortality Due to Breast and Colorectal Cancer
Authors: Imre Boncz, Andor Sebestyén, István Pintér, József Betlehem, Ildikó Kriszbacher, Tibor Csere, László Mangel, József Bódis
Journal: Journal of Clinical Oncology (2007)

observed FOXP3 protein expression exclusively in infiltrating lymphocytes, 2,3 a recent article by Zuo et al 4 reported the expression of both FOXP3 protein and mRNA in human breast epithelial cells.Their FOXP3 protein expression data, obtained using a polyclonal antibody, are contrary to our findings with the anti-FOXP3 236A/E7 monoclonal antibody 2,3 and studies are ongoing to investigate the reasons for this discrepancy.However, using real-time PCR this group have demonstrated FOXP3 mRNA expression in human and murine mammary epithelial cells. 4These data thus suggest that the quantification of FOXP3 mRNA levels is not a surrogate marker for Tregs within the breast tumor microenvironment.Moreover, as it is reported that normal breast tissue has high epithelial FOXP3 mRNA expression 4 and low Treg numbers, 2 while tumors have reduced epithelial FOXP3 mRNA expression 4 and increased Treg numbers 2 then it is possible that these factors may cancel out and obscure any clinical significance dependent on Treg-derived FOXP3 expression.This may also have contributed to the lack of clinical significance provided by this study of FOXP3 mRNA expression in breast cancer patients.