tbuckley/cabot-search huggingface dataset:
Oxidative Stress and Endothelial Function in Chronic Renal Failure
Authors: Margus Annuk, Mihkel Zilmer, Lars Lind, Torbjörn Linde, Bengt Fellström
Journal: Journal of the American Society of Nephrology (2001)

This study aimed to investigate the relationship between oxidative stress and endothelium-dependent vasodilation in patients with chronic renal failure (CRF). Thirty-seven patients with CRF underwent evaluation of endothelium-dependent vasodilation and endothelium-independent vasodilation by means of forearm blood flow measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (evaluating endothelium-dependent vasodilation) and sodium nitroprusside (evaluating endothelium-independent vasodilation). Lag phase of lipoprotein fraction to oxidation, total antioxidative activity, diene conjugates, thiobarbituric acid reactive substances, lipid hydroperoxide, reduced glutathione (GSH), oxidized GSH (GSSG), and the GSH redox ratio (GSSG/GSH) were all measured as markers of oxidative stress. Two groups of healthy subjects (61 and 37 subjects, respectively) were used as controls. In one group, oxidative stress markers were measured, whereas endothelium-dependent vasodilation and endothelium-independent vasodilation were assessed in the other group. Compared with controls, the patients with renal insufficiency had an impaired endothelium-dependent vasodilation, a shorter lag phase of lipoprotein fraction, and higher levels of diene conjugates, lipid hydroperoxide, and GSSG levels. The GSSG/GSH ratio was lower in patients with CRF. Endothelium-dependent vasodilation was positively correlated with total antioxidative activity (r = 0.41, P = 0.016), GSH (r = 0.44, P < 0.0098), and lag phase of LDL (r = 0.35, P = 0.036) and negatively correlated with GSSG (r = -0.40, P < 0.018), GSSG/GSH (r = -0.47, P = 0.0057), and diene conjugates (r = -0.53 P < 0.0015) in patients with CRF. These results show that an impaired endothelium vasodilation function and oxidative stress are related to each other in patients with CRF.
A Paclitaxel-Hyaluronan Bioconjugate Targeting Ovarian Cancer Affords a Potent <i>In vivo</i> Therapeutic Activity
Authors: Alessandra Banzato, Sara Bobisse, Maria Rondina, Davide Renier, Fabio Bettella, Giovanni Esposito, Luigi Quintieri, Laura Meléndez-Alafort, Ulderico Mazzi, Paola Zanovello, Antonio Rosato
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study was designed to evaluate the pharmacologic and biological properties of a paclitaxel-hyaluronan bioconjugate (ONCOFID-P) against IGROV-1 and OVCAR-3 human ovarian cancer xenografts following i.p. administration. Experimental Design: In vitro tumor sensitivity to ONCOFID-P was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, whereas bioconjugate interaction with cells was studied cytofluorimetrically and by confocal microscopy. In vivo toxicity was assessed by a single-dose maximum-tolerated dose, peripheral blood cell count determination and by histologic analysis. Biodistribution of the compound was evaluated with a small animal–dedicated scintigraphy gamma camera following injection of 99mTc-labeled ONCOFID-P. Pharmacokinetic analysis was also carried out. Female severe combined immunodeficiency mice implanted with ovarian cancer cells underwent treatment with ONCOFID-P or free paclitaxel starting from day 7 or 14 after tumor injection, and survivals were compared. Results: ONCOFID-P interacted with CD44, entered cells through a receptor-mediated mechanism, and exerted a concentration-dependent inhibitory effect against tumor cell growth. After i.p. administration, the bioconjugate distributed quite uniformly within the peritoneal cavity, was well-tolerated, and was not associated with local histologic toxicity. Pharmacokinetic studies revealed that blood levels of bioconjugate-derived paclitaxel were much higher and persisted longer than those obtained with the unconjugated free drug. Intraperitoneal treatment of tumor-bearing mice with the bioconjugate revealed that ONCOFID-P exerted a relevant increase in therapeutic activity compared with free drug. Conclusions: ONCOFID-P significantly improved results obtained with conventional paclitaxel, in terms of in vivo tolerability and therapeutic efficacy; these data strongly support its development for locoregional treatment of ovarian cancer.
Human neural stem cells alleviate Alzheimer-like pathology in a mouse model
Authors: Il-Shin Lee, Kwangsoo Jung, Il-Sun Kim, Haejin Lee, Miri Kim, Seokhwan Yun, Kyujin Hwang, Jeong Eun Shin, Kook In Park
Journal: Molecular Neurodegeneration (2015)

Alzheimer’s disease (AD) is an inexorable neurodegenerative disease that commonly occurs in the elderly. The cognitive impairment caused by AD is associated with abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, which are accompanied by inflammation. Neural stem cells (NSCs) are self-renewing, multipotential cells that differentiate into distinct neural cells. When transplanted into a diseased brain, NSCs repair and replace injured tissues after migration toward and engraftment within lesions. We investigated the therapeutic effects in an AD mouse model of human NSCs (hNSCs) that derived from an aborted human fetal telencephalon at 13 weeks of gestation. Cells were transplanted into the cerebral lateral ventricles of neuron-specific enolase promoter-controlled APPsw-expressing (NSE/APPsw) transgenic mice at 13 months of age. Implanted cells extensively migrated and engrafted, and some differentiated into neuronal and glial cells, although most hNSCs remained immature. The hNSC transplantation improved spatial memory in these mice, which also showed decreased tau phosphorylation and Aβ42 levels and attenuated microgliosis and astrogliosis. The hNSC transplantation reduced tau phosphorylation via Trk-dependent Akt/GSK3β signaling, down-regulated Aβ production through an Akt/GSK3β signaling-mediated decrease in BACE1, and decreased expression of inflammatory mediators through deactivation of microglia that was mediated by cell-to-cell contact, secretion of anti-inflammatory factors generated from hNSCs, or both. The hNSC transplantation also facilitated synaptic plasticity and anti-apoptotic function via trophic supplies. Furthermore, the safety and feasibility of hNSC transplantation are supported. These findings demonstrate the hNSC transplantation modulates diverse AD pathologies and rescue impaired memory via multiple mechanisms in an AD model. Thus, our data provide tangible preclinical evidence that human NSC transplantation could be a safe and versatile approach for treating AD patients.
Incidence, 30-day case-fatality rate, and prognosis of stroke in Iquique, Chile: a 2-year community-based prospective study (PISCIS project)
Authors: Pablo M Lavados, Claudio Sacks, Liliana Prina, Arturo Escobar, Claudia Tossi, Fernando Araya, Walter Feuerhake, Marcelo Galvez, Rodrigo Salinas, Gonzalo Alvarez
Journal: The Lancet (2005)
Quantitative Trait Analysis Reveals Transforming Growth Factor-β2 as a Positive Regulator of Early Hematopoietic Progenitor and Stem Cell Function
Authors: Jessica C. Langer, Els Henckaerts, Jonathan Orenstein, Hans-Willem Snoeck
Journal: The Journal of Experimental Medicine (2004)

Elucidation of pathways involved in mouse strain–dependent variation in the hematopoietic stem cell (HSC) compartment may reveal novel mechanisms relevant in vivo. Here, we demonstrate genetically determined variation in the proliferation of lin−Sca1++kit+ (LSK) primitive hematopoietic progenitor cells in response to transforming growth factor-β (TGF-β) 2, the dose response of which was biphasic with a stimulatory effect at low concentrations. In contrast, the dose responses of TGF-β1 or -β3 were inhibitory and did not show mouse strain–dependent variation. A quantitative trait locus (QTL) for the effect of TGF-β2 was identified on chromosome 4 overlapping with a QTL regulating the frequency of LSK cells. These overlapping QTL were corroborated by the observation that the frequency of LSK cells is lower in adult Tgfb2+/− mice than in wild-type littermates, indicating that TGF-β2 is a genetically determined positive regulator LSK number in vivo. Furthermore, adult Tgfb2+/− mice have a defect in competitive repopulation potential that becomes more pronounced upon serial transplantation. In fetal TGF-β2–deficient HSCs, a defect only appears after serial reconstitution. These data suggest that TGF-β2 can act cell autonomously and is important for HSCs that have undergone replicative stress. Thus, TGF-β2 is a novel, genetically determined positive regulator of adult HSCs.
Three-dimensional high-definition optical coherence tomography image acquisition procedure for basal cell carcinoma
Authors: M. Boone, M. Suppa, M. Miyamoto, A. Marneffe, G.B.E. Jemec, G. Pellacani, V. Del Marmol
Journal: British Journal of Dermatology (2014)

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Heart Failure and Echocardiographic Changes During Long-term Follow-up of Patients With Sick Sinus Syndrome Randomized to Single-Chamber Atrial or Ventricular Pacing
Authors: Jens Cosedis Nielsen, Henning Rud Andersen, Poul Erik Bloch Thomsen, Leif Thuesen, Peter Thomas Mortensen, Thomas Vesterlund, Anders Kirstein Pedersen
Journal: Circulation (1998)

Background —In patients with sick sinus syndrome, choice of pacing mode has been implicated in the development of congestive heart failure. Methods and Results —A total of 225 consecutive patients with sick sinus syndrome and intact atrioventricular conduction were randomized to either single-chamber atrial pacing (n=110) or single-chamber ventricular pacing (n=115). Clinical assessment included New York Heart Association classification, medication, and M-mode echocardiography before pacemaker implantation, after 3 months, and subsequently once every year. At long-term follow-up (mean, 5.5±2.4 years), NYHA class was higher in the ventricular group than in the atrial group (NYHA class I/II/III/IV: 65/44/4/0 versus 84/22/2/1 patients, P =.010). Increase in NYHA class during follow-up was observed in 35 of 113 patients in the ventricular group versus 10 of 109 in the atrial group ( P &lt;.0005). Increase in dose of diuretics from randomization to last follow-up was significantly higher in the ventricular group than in the atrial group (21±49 versus 8±42 mg furosemide/d, P =.033). The left ventricular fractional shortening decreased significantly in the ventricular group (from 0.36±0.12 to 0.31±0.08, P &lt;.0005) but not in the atrial group (from 0.35±0.13 to 0.33±0.09, P =.087). The left atrial diameter increased significantly in both treatment groups (ventricular group: from 34±7 to 41±7 mm, P &lt;.0005; atrial group: from 34±6 to 37±7 mm, P =.002), but the increase was significantly higher in the ventricular group than in the atrial group ( P &lt;.0005). Conclusions —During long-term follow-up, ventricular pacing is associated with a higher incidence of congestive heart failure and consumption of diuretics than atrial pacing. This is accompanied by a decrease in left ventricular fractional shortening and an increased dilatation of the left atrium in the ventricular paced patients.
Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice
Authors: D. S. Southam, R. Ellis, J. Wattie, S. Young, M. D. Inman
Journal: European Respiratory Journal (2008)

Despite the effectiveness of corticosteroids at resolving airway inflammation, they are only moderately effective at attenuating airway hyperresponsiveness (AHR). The extent to which corticosteroids are able to reverse or inhibit the development of sustained AHR is not known. The present study aimed to determine whether budesonide can resolve and or prevent the development of sustained AHR in mice. Mice were chronically exposed to allergen and treated with budesonide either: 1) briefly during the final weeks of exposure to allergen; 2) prolonged concurrently throughout exposure to allergen; or 3) delayed following final exposure to allergen. AHR was assessed 24 h (brief treatment) or 4 weeks (prolonged concurrent and delayed treatments) following final exposure to allergen. Brief budesonide intervention significantly attenuated the inflammation-associated AHR assessed immediately following final exposure to allergen. Similarly, prolonged concurrent budesonide treatment prevented the development of sustained AHR. Delayed budesonide intervention, however, did not resolve sustained AHR. In conclusion, the early introduction and, importantly, the persistence of corticosteroid treatment prevented the development of sustained airway hyperresponsiveness; however, the inability of corticosteroids to reverse established airway dysfunction indicates a limitation in their use for the complete, long-term management of airway hyperresponsiveness.
MR-Guided Biopsy of the Prostate: An Overview of Techniques and a Systematic Review
Authors: Kirsten M. Pondman, Jurgen J. Fütterer, Bennie ten Haken, Leo J. Schultze Kool, J. Alfred Witjes, Thomas Hambrock, Katarzyna J. Macura, Jelle O. Barentsz
Journal: European Urology (2008)
Role of the oesophagus in asthma induced by the ingestion of ice and acid.
Authors: N M Wilson, N Chudry, M Silverman
Journal: Thorax (1987)

Twelve Asian patients with a history of asthma exacerbated by ingestion of ice and acidic drinks were selected for study. To determine the site of response to ingested ice and acid they were challenged with ice or dilute hydrochloric acid, which was orally retained on one day and swallowed on another. On a third day a placebo was given. The airway response was assessed by measuring FEV1 and the provocative concentration of histamine that reduced the FEV1 by at least 20% (PC20). There was no significant change in FEV1 or histamine PC20 after placebo or the orally retained challenges for the group as a whole or for any individual. After the ice and hydrochloric acid had been swallowed there was a small but statistically significant mean fall in FEV1, increasing to a maximum 90 minutes after ingestion, together with a significant increase in bronchial responsiveness. As conditioning of the inspired air would have been similar after orally retained and after swallowed ice or acid, the response is likely to be due to oesophageal stimulation. The mechanism of the response to oesophageal stimulation is unclear, but the slow time course seems to preclude a simple neural reflex.
Finasteride and bicalutamide as primary hormonal therapy in patients with advanced adenocarcinoma of the prostate
Authors: M.-H. Tay, D.S. Kaufman, M.M. Regan, S.B. Leibowitz, D.J. George, P.G. Febbo, J. Manola, M.R. Smith, I.D. Kaplan, P.W. Kantoff, W.K. Oh
Journal: Annals of Oncology (2004)
Need for Centers to Care for Patients With Acute Coronary Syndromes
Authors: Robert M. Califf, David P. Faxon
Journal: Circulation (2003)

cute myocardial infarction (MI) characterized by ST-segment elevation on the ECG has been the subject of more randomized trials and outcome studies than any other area of medicine.Recently, non-STelevation acute coronary syndromes (ACS) have taken an equal position in terms of clinical study and clinical relevance.Additionally, through a series of frustrations 1 and triumphs, 2 the critical nature of prehospital management of ACS has been underscored.This attention is appropriate, given the dominance of coronary artery disease (CAD) as the leading global cause of death and disability.Despite this abundance of evidence, however, ample studies have reported the common failure to deliver the standard of care in clinical practice.We believe that the establishment of regional centers for ACS, if linked with the communities in which they exist and if approached in a reasonable fashion with appropriate financial incentives, would result in much more effective and efficient care of this dominant public health problem.
Genomic Organization of Amplified <i>MYC</i> Genes Suggests Distinct Mechanisms of Amplification in Tumorigenesis
Authors: John Herrick, Chiara Conti, Sebastien Teissier, Francoise Thierry, Jérôme Couturier, Xavier Sastre-Garau, Michel Favre, Gérard Orth, Aaron Bensimon
Journal: Cancer Research (2005)

Abstract Integration of the human papillomavirus (HPV) genome into the host genome is associated with the disruption of the HPV E2 gene and with amplification and rearrangement of the viral and flanking cellular sequences. Molecular characterization of the genomic structures of coamplified HPV sequences and oncogenes provides essential information concerning the mechanisms of amplification and their roles in carcinogenesis. Using fluorescent hybridization on stretched DNA molecules in two cervical cancer–derived cell lines, we have elucidated the genomic structures of amplified regions containing HPV/myc genes over several hundreds of kilobases. Direct visualization of hybridization signals on individual DNA molecules suggests that overreplication and breakage-fusion-bridge–type mechanisms are involved in the genomic instability associated with HPV cervical cancers. Further analysis from two other genital cancer–derived cell lines reveals a recurrent motif of amplification, probably generated by a common mechanism involving overreplication upon viral integration. Interestingly, different amplification patterns seem to be correlated with the disease outcome, thus providing new insights into HPV-related cancer development and tumor progression.
Prevalence and Characteristics of Nonpolypoid Colorectal Neoplasm in an Asymptomatic and Average-Risk Chinese Population
Authors: Han–Mo Chiu, Jaw–Town Lin, Chien–Chuan Chen, Yi–Chia Lee, Wei–Chih Liao, Jin–Tung Liang, Chia–Tung Shun, Hsiu–Po Wang, Ming–Shiang Wu
Journal: Clinical Gastroenterology and Hepatology (2008)
Dipeptidase deficiency and malabsorption of glycylglycine in disease states
Authors: F. Sadikali
Journal: Gut (1971)

The activities of jejunal mucosal peptide hydrolases for glycylglycine, glycyl-L-leucine and L-leucylglycine, were assayed in 37 patients. Eight patients, four of whom had Crohn's disease, were found to have a marked reduction in the activity of glycylglycine dipeptidase and, to a lesser extent, of the other two hydrolases. Although absorption of glycine in the two groups was similar, there was malabsorption of glycylglycine in the patients with reduced dipeptidases as shown by a flat absorption curve. The importance of peptide hydrolases of small-intestinal mucosa in the final digestion of proteins, and the implications of peptidase deficiency in disease states is discussed. It is concluded that significant peptidase deficiency may occur even when the mucosa is otherwise histologically completely normal, similar to some states of disaccharidase deficiency described in recent years.
Comparative Functional Analysis of <i>DPYD</i> Variants of Potential Clinical Relevance to Dihydropyrimidine Dehydrogenase Activity
Authors: Steven M. Offer, Croix C. Fossum, Natalie J. Wegner, Alexander J. Stuflesser, Gabriel L. Butterfield, Robert B. Diasio
Journal: Cancer Research (2014)

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of the uracil catabolic pathway, being critically important for inactivation of the commonly prescribed anti-cancer drug 5-fluorouracil (5-FU). DPD impairment leads to increased exposure to 5-FU and, in turn, increased anabolism of 5-FU to cytotoxic nucleotides, resulting in more severe clinical adverse effects. Numerous variants within the gene coding for DPD, DPYD, have been described, although only a few have been demonstrated to reduce DPD enzyme activity. To identify DPYD variants that alter enzyme function, we expressed 80 protein-coding variants in an isogenic mammalian system and measured their capacities to convert 5-FU to dihydro-fluorouracil, the product of DPD catabolism. The M166V, E828K, K861R, and P1023T variants exhibited significantly higher enzyme activity than wild-type DPD (120%, P = 0.025; 116%, P = 0.049; 130%, P = 0.0077; 138%, P = 0.048, respectively). Consistent with clinical association studies of 5-FU toxicity, the D949V substitution reduced enzyme activity by 41% (P = 0.0031). Enzyme activity was also significantly reduced for 30 additional variants, 19 of which had <25% activity. None of those 30 variants have been previously reported to associate with 5-FU toxicity in clinical association studies, which have been conducted primarily in populations of European ancestry. Using publicly available genotype databases, we confirmed the rarity of these variants in European populations but showed that they are detected at appreciable frequencies in other populations. These data strongly suggest that testing for the reported deficient DPYD variations could dramatically improve predictive genetic tests for 5-FU sensitivity, especially in individuals of non-European descent.
A video system for investigating breathing disorders during sleep.
Authors: C J Griffiths, B G Cooper, G J Gibson
Journal: Thorax (1991)

A system has been developed for investigating breathing during sleep that superimposes physiological signals on a video image of the patient, with the combined image plus sound recorded on video tape for later analysis. Signals normally displayed include oxygen saturation, airflow, chest wall motion, electroencephalogram, and electrooculogram; but others can be recorded if desired. The information is displayed on a timebase appropriate for the recognition and analysis of respiratory events during sleep. In addition, use is made of normally invisible video lines to record the analogue voltage waveforms so that on replay this information can be displayed on a fast timebase for analysing the more rapidly changing waveforms of electrophysiological signals. The system allows detailed polysomnography to be performed in the normal ward setting with the subject monitored overnight by the nursing staff. Subsequent analysis of the synchronised video, audio, and analogue signals allows measurement of the conventional indices obtained by polysomnography and aids their interpretation.
NOTES ON SMALL-POX
Authors: W. M. Wanklyn
Journal: BMJ (1922)

NOTES ON SMALL-POX.into the disinfection of wool and hairs infected with anthrax spores, and also into the practice and effective methods of preventing infection among flocks.It is to report on these subjects to the governing body of the International Labour Office in time for the consideration of the International Labour Conference in 1923.It is also to inquire into the possibilities of dealing with infection by anthrax from hides, skins, and other materials.