tbuckley/cabot-search huggingface dataset:
Megalin-Mediated Specific Uptake of Chitosan/siRNA Nanoparticles in Mouse Kidney Proximal Tubule Epithelial Cells Enables AQP1 Gene Silencing
Authors: Shan Gao, San Hein, Frederik Dagnæs-Hansen, Kathrin Weyer, Chuanxu Yang, Rikke Nielsen, Erik I Christensen, Robert A Fenton, Jørgen Kjems
Journal: Theranostics (2014)

RNAi-based strategies provide a great therapeutic potential for treatment of various human diseases including kidney disorders, but face the challenge of in vivo delivery and specific targeting.The chitosan delivery system has previously been shown to target siRNA specifically to the kidneys in mice when administered intravenously.Here we confirm by 2D and 3D bioimaging that chitosan formulated siRNA is retained in the kidney for more than 48 hours where it accumulates in proximal tubule epithelial cells (PTECs), a process that was strongly dependent on the molecular weight of chitosan.Chitosan/siRNA nanoparticles, administered to chimeric mice with conditional knockout of the megalin gene, distributed almost exclusively in cells that expressed megalin, implying that the chitosan/siRNA particle uptake was mediated by a megalin-dependent endocytotic pathway.Knockdown of the water channel aquaporin 1 (AQP1) by up to 50% in PTECs was achieved utilizing the systemic i.v.delivery of chitosan/AQP1 siRNA in mice.In conclusion, specific targeting PTECs with the chitosan nanoparticle system may prove to be a useful strategy for knockdown of specific genes in PTECs, and provides a potential therapeutic strategy for treating various kidney diseases.
Evaluation of a QRS scoring system for estimating myocardial infarct size. I. Specificity and observer agreement.
Authors: G S Wagner, C J Freye, S T Palmeri, S F Roark, N C Stack, R E Ideker, F E Harrell, R H Selvester
Journal: Circulation (1982)

We evaluated a simplified version of a previously developed QRS scoring system for estimating infarct size using observations of Q- and R-wave durations and R/Q and R/S amplitude ratios in the standard 12-lead ECG. Groups of subjects with a minimal likelihood of having myocardial infarcts and minimal likelihood of having common noninfarction sources of QRS modification were studied to establish the specificity of each of the 37 criteria. Only two criteria required modification to achieve 95% specificity. These 37 criteria form the basis of a 29-point QRS scoring system. A 98% specificity was achieved when a score of more than 2 points was required to identify a myocardial infarct. Fifty patients were studied to determine the intra- and interobserver agreement with this scoring system. Each criterion achieved at least 91% intra- and interobserver agreement. These impressive levels of specificity and observer agreement must be matched by high sensitivity of the scoring system and a good correlation between the point score and infarct size in patients with proven infarcts if the point score is to be useful for detecting and sizing infarcts. Sensitivity and correlation between point score and infarct size are evaluated in later studies in this series. The standard ECG is inexpensive and can be obtained repetitively and noninvasively; its QRS complex may be an important means of estimating the size, presence and location of myocardial infarcts.
T-Regulatory Cells and Programmed Death 1<sup>+</sup> T Cells Contribute to Effector T-Cell Dysfunction in Patients with Chronic Obstructive Pulmonary Disease
Authors: Suresh Gopi Kalathil, Amit Anand Lugade, Vandana Pradhan, Austin Miller, Ganapathi Iyer Parameswaran, Sanjay Sethi, Yasmin Thanavala
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Previous studies from our laboratory have shown that peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD) prone to exacerbations with nontypeable Haemophilus influenzae have impaired responses to lipoprotein P6. We hypothesized that an underlying immunosuppressive network could be responsible for the defective antibacterial immunity observed in these patients. We evaluated T regulatory cells (Tregs), myeloid-derived suppressor cells (MDSC), and exhausted T effector cells (programmed death 1 [PD-1]+) in patients with COPD, because these cells are known to play a pivotal role in suppressing immune responses.Objectives: We performed an in-depth characterization of Tregs, T effector cells, and MDSC in COPD and correlated their levels and function with disease severity.Methods: Treg, effector T cell, and MDSC frequency from patients with COPD and healthy subjects’ PBMCs were analyzed by flow cytometry. Treg immunosuppressive capacity was measured by in vitro suppression assay. The frequency of interferon-γ producing T cells and T-cell proliferation were measured after blocking CTLA-4 and PD-1. Plasma proinflammatory and immunosuppressive cytokine levels were measured.Measurements and Main Results: Significantly increased levels of Tregs, MDSC, and PD-1+ exhausted effector T cells were present in patients with COPD compared with healthy subjects. Tregs from patients with COPD suppressed P6-specific T-cell proliferation to a greater extent than Tregs from healthy subjects. Plasma levels of Treg-generated cytokines, IL-10, and transforming growth factor-β were elevated. Blockade of CTLA-4 resulted in significant augmentation of T-cell IFN-γ production in patients with COPD.Conclusions: Functionally suppressive Tregs, MDSCs, and exhausted PD-1+ T cells contribute to effector T-cell dysfunction in COPD.
Single aetiology and dual associations of cardiac cancer
Authors: Johannes Lenglinger, Margit Eisler, Martin Riegler
Journal: Gut (2007)

With interest we read the article by Hansen et al. ( Gut 2007; 56 :918–25). The authors have to be congratulated on their contribution which profoundly adds to our understanding of the pathophysiology leading to oesophageal and gastric cancer. In addition, the paper points out the difficulties we have to correctly assign tumours of the oesophago-gastric junction (oesophageal vs gastric?). Cardiac cancers were subtyped for their associations with serum anti- Helicobacter pylori IgG antibody titer and biochemical markers of loss of gastric secretory function associated with atrophy (pepsinogen I/II ratio and serum gastrin concentration). However, the anatomic criterium to define cardiac carcinoma, that is, tumours centred within 2 cm distal to the oesophago-gastric junction, is inaccurate. Interpretation of the data should be conducted with the inclusion of clear, anatomical and histopathological criteria.

It is well accepted that cardiac cancer and adenocarcinoma of the oesophagus share epidemiological and pathogenetic features.1,2 After birth the oesophagus is lined by squamous epithelium, whereas the stomach is lined by gastric oxyntic mucosa (with parietal and chief cells).1,3 Due to gastro-oesophageal reflux, squamous epithelium is …
Live Attenuated versus Inactivated Influenza Vaccine in Infants and Young Children
Authors: Robert B. Belshe, Kathryn M. Edwards, Timo Vesikari, Steven V. Black, Robert E. Walker, Micki Hultquist, George Kemble, Edward M. Connor
Journal: New England Journal of Medicine (2007)

Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies. To evaluate alternative vaccine approaches, we compared the safety and efficacy of intranasally administered live attenuated influenza vaccine with those of inactivated vaccine in infants and young children.
Effects of Ventilation Strategies on the Efficacy of Exogenous Surfactant Therapy in a Rabbit Model of Acute Lung Injury
Authors: YUSHI ITO, STUART E. E. MANWELL, CAROLYN L. KERR, RUUD A. W. VELDHUIZEN, LI-JUAN YAO, DAVE BJARNESON, LYNDA A. McCAIG, ADRIENNE J. BARTLETT, JAMES F. LEWIS
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We evaluated the effects of various ventilation strategies on the efficacy of exogenous surfactant therapy in lung-injured adult rabbits. Lung injury was induced by repetitive whole-lung saline lavage followed by mechanical ventilation. Three hours after the final lavage, 100 mg lipid/kg bovine lipid extract surfactant was instilled. After confirmation of similar responses to exogenous surfactant, animals were then randomized to one of four ventilation groups; (1) Normal tidal volume (Vt) (5 cm H2O): Vt = 10 ml/kg, respiratory rate (RR) = 30/min, positive end-expiratory pressure (PEEP) = 5 cm H2O; (2) Normal Vt (9 cm H2O): Vt = 10 ml/kg, RR = 30/min, PEEP = 9 cm H2O; (3) Low Vt (5 cm H2O): Vt = 5 ml/kg, RR = 60/min, PEEP = 5 cm H2O; (4) Low Vt (9 cm H2O): Vt = 5 ml/kg, RR = 60/min, PEEP = 9 cm H2O. Animals were ventilated for an additional 3 h and then killed, and lung lavage fluid was analyzed. Animals ventilated with the low-Vt modes (Low Vt [5 cm H2O] and Low Vt [9 cm H2O]) had higher PaO2 values (430 ± 7 mm Hg and 425 ± 18 mm Hg versus 328 ± 13 mm Hg) and higher percentages of surfactant in large aggregate forms (83 ± 2% and 82 ± 2% versus 67 ± 4%) at 3 h after treatment than did the Normal Vt (5 cm H2O) group (p < 0.05). Increasing the PEEP level was beneficial for a short period after surfactant administration to maintain oxygenation, but did not affect exogenous surfactant aggregate conversion. We speculate that ventilation strategies resulting in low exogenous surfactant aggregate conversion will result in superior physiologic responses to exogenous surfactant.
Migration and Differentiation of Autoreactive B-1 Cells Induced by Activated γ/δ T Cells in Antierythrocyte Immunoglobulin Transgenic Mice
Authors: Norihiko Watanabe, Koichi Ikuta, Sidonia Fagarasan, Shujiro Yazumi, Tsutomu Chiba, Tasuku Honjo
Journal: The Journal of Experimental Medicine (2000)

Using normal and transgenic (Tg) mice, we have shown that peritoneal B-1 cells are activated by administration of cytokines or lipopolysaccharide and migrate to other lymphoid organs where they differentiate into antibody-secreting cells. However, little is known about the process of B-1 cell migration and differentiation in vivo. We developed a mouse line by crossing the antierythrocyte antibody Tg mice (HL mice) with TCR-γ/δ Tg mice specific for a self-thymus leukemia (TL) antigen in the recombination activating gene (RAG)2−/− background. In the presence of the self-antigen, Tg γ/δ T cells increased in number and manifested activated phenotypes. Peritoneal B-1 cells in these mice migrated into mesenteric lymph nodes and differentiated into autoantibody-secreting cells, resulting in strong autoimmune hemolytic anemia. Furthermore, transfer of RAG2−/− × HL bone marrow or peritoneal cells into the peritoneal cavity of RAG2−/− × TCR-γ/δ Tg mice gave rise to donor-derived B-1 cells in mesenteric lymph nodes, and these cells produced the autoantibody. Thus, this study demonstrates that the migration of B-1 cells and differentiation into the antibody-secreting cells can be induced by noncognate T cell help and implies the possibility that γ/δ T cells may induce B-1 cell differentiation in vivo.
Isolation prevalence of pulmonary non-tuberculous mycobacteria in Ontario, 1997 2003
Authors: T. K Marras, P. Chedore, A. M Ying, F. Jamieson
Journal: Thorax (2007)

The prevalence of pulmonary non-tuberculous mycobacteria (NTM) infection is reportedly increasing. A study was undertaken of the "isolation prevalence" of pulmonary NTM in Ontario, Canada between 1997 and 2003 and the frequency of pulmonary NTM "disease".In a retrospective cohort, the "isolation prevalence" was studied by reviewing all positive NTM culture results from the Tuberculosis and Mycobacteriology Laboratory, Ministry of Health and Long-Term Care in Toronto from 1997 to 2003. This laboratory identifies at least 90% of NTM isolates in Ontario, Canada. Prevalence was compared between years using a negative binomial model. To study the frequency of "disease" (defined by American Thoracic Society criteria), the records of patients who had an isolate in 2003 and had been assessed at our hospital were reviewed.22,247 pulmonary isolates were obtained from 10,231 patients. The "isolation prevalence" of all species (excluding Mycobacterium gordonae) was 9.1/100,000 in 1997, rising to 14.1/100,000 by 2003 (p<0.0001) with a mean annual increase of 8.4%. Similar increases were observed for individual species. 200 patients assessed at our institution were studied using American Thoracic Society criteria for "disease". Microbiological criteria were fulfilled by 37%. Of patients with adequate data, 74% fulfilled clinical criteria, 77% fulfilled radiological criteria and 33% fulfilled all criteria.The "isolation prevalence" of pulmonary NTM has significantly and rapidly increased in Ontario; a sizeable proportion of patients are likely to have "disease".
Validation of Walk Score for estimating access to walkable amenities
Authors: Lucas J Carr, Shira I Dunsiger, Bess H Marcus
Journal: British Journal of Sports Medicine (2010)

Background Proximity to walkable destinations or amenities is thought to influence physical activity behaviour. Previous efforts attempting to calculate neighbourhood walkability have relied on self-report or time-intensive and costly measures. Walk Score is a novel and publicly available website that estimates neighbourhood walkability based on proximity to 13 amenity categories (eg, grocery stores, coffee shops, restaurants, bars, movie theatres, schools, parks, libraries, book stores, fitness centres, drug stores, hardware stores, clothing/music stores). Objective The purpose of this study is to test the validity and reliability of Walk Score for estimating access to objectively measured walkable amenities. Methods Walk Scores of 379 residential/non-residential addresses in Rhode Island were manually calculated. Geographic information systems (GIS) was used to objectively measure 4194 walkable amenities in the 13 Walk Score categories. GIS data were aggregated from publicly available data sources. Sums of amenities within each category were matched to address data, and Pearson correlations were calculated between the category sums and address Walk Scores. Results Significant correlations were identified between Walk Score and all categories of aggregated walkable destinations within a 1-mile buffer of the 379 residential and non-residential addresses. Test–retest reliability correlation coefficients for a subsample of 100 addresses were 1.0. Conclusion These results support Walk Score as a reliable and valid measure of estimating access to walkable amenities. Walk Score may be a convenient and inexpensive option for researchers interested in exploring the relationship between access to walkable amenities and health behaviours such as physical activity.
Long-Term Effects of Arterial Stenting on Kidney Functionfor Patients with Ostial Atherosclerotic Renal Artery Stenosis and Renal Insufficiency
Authors: JAAP J. BEUTLER, JACOBINE M. A. VAN AMPTING, PETER J. G. VAN DE VEN, HEIN A. KOOMANS, FREDERIK J. A. BEEK, AREND-JAN J. WOITTIEZ, WILLEM P. T. M. MALI
Journal: Journal of the American Society of Nephrology (2001)

Abstract. It is uncertain whether renal artery stent placement in patients with atherosclerotic renovascular renal failure can prevent further deterioration of renal function. Therefore, the effects of renal artery stent placement, followed by patency surveillance, were prospectively studied in 63 patients with ostial atherosclerotic renal artery stenosis and renal dysfunction ( i.e. , serum creatinine concentrations of &gt;120 μmol/L (median serum creatinine concentration, 171 μmol/L; serum creatinine concentration range, 121 to 650 μmol/L). Pre-stent renal (dys) function was stable for 28 patients and declining for 35 patients (defined as a serum creatinine concentration increase of ≥20% in 12 mo). The median follow-up period was 23 mo (interquartile range, 13 to 29 mo). Angioplasty to treat restenosis was performed in 12 cases. Five patients reached end-stage renal failure within 6 mo, and this was related to stent placement in two cases. Two other patients died or were lost to follow-up monitoring within 6 mo, with stable renal function. For the remaining 56 patients, the treatment had no effect on serum creatinine levels if function had previously been stable; if function had been declining, median serum creatinine concentrations improved in the first 1 yr [from 182 μmol/L (135 to 270 μmol/L) to 154 μmol/L (127 to 225 μmol/L); P &lt; 0.05] and remained stable during further follow-up monitoring. In conclusion, stent placement, followed by patency surveillance, to treat ostial atherosclerotic renal artery stenosis can stabilize declining renal function. For patients with stable renal dysfunction, the usefulness is less clear. The possible advantages must be weighed against the risk of renal failure advancement with stent placement.
Outcomes of Critically Ill Patients With Hematologic Malignancies: Prospective Multicenter Data From France and Belgium—A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study
Authors: Elie Azoulay, Djamel Mokart, Frédéric Pène, Jérôme Lambert, Achille Kouatchet, Julien Mayaux, François Vincent, Martine Nyunga, Fabrice Bruneel, Louise-Marie Laisne, Antoine Rabbat, Christine Lebert, Pierre Perez, Marine Chaize, Anne Renault, Anne-Pascale Meert, Dominique Benoit, Rebecca Hamidfar, Mercé Jourdain, Michael Darmon, Benoit Schlemmer, Sylvie Chevret, Virginie Lemiale
Journal: Journal of Clinical Oncology (2013)

Purpose Patients with hematologic malignancies are increasingly admitted to the intensive care unit (ICU) when life-threatening events occur. We sought to report outcomes and prognostic factors in these patients. Patients and Methods Ours was a prospective, multicenter cohort study of critically ill patients with hematologic malignancies. Health-related quality of life (HRQOL) and disease status were collected after 3 to 6 months. Results Of the 1,011 patients, 38.2% had newly diagnosed malignancies, 23.1% were in remission, and 24.9% had received hematopoietic stem-cell transplantations (HSCT, including 145 allogeneic). ICU admission was mostly required for acute respiratory failure (62.5%) and/or shock (42.3%). On day1, 733 patients (72.5%) received life-supporting interventions. Hospital, day-90, and 1-year survival rates were 60.7%, 52.5%, and 43.3%, respectively. By multivariate analysis, cancer remission and time to ICU admission less than 24 hours were associated with better hospital survival. Poor performance status, Charlson comorbidity index, allogeneic HSCT, organ dysfunction score, cardiac arrest, acute respiratory failure, malignant organ infiltration, and invasive aspergillosis were associated with higher hospital mortality. Mechanical ventilation (47.9% of patients), vasoactive drugs (51.2%), and dialysis (25.9%) were associated with mortality rates of 60.5%, 57.5%, and 59.2%, respectively. On day 90, 80% of survivors had no HRQOL alterations (physical and mental health similar to that of the overall cancer population). After 6 months, 80% of survivors had no change in treatment intensity compared with similar patients not admitted to the ICU, and 80% were in remission. Conclusion Critically ill patients with hematologic malignancies have good survival, disease control, and post-ICU HRQOL. Earlier ICU admission is associated with better survival.
A Diagnostic Problem: An Unusual Case of Hepatitis
Authors: J. L. Fluker
Journal: BMJ (1945)

remain away from employment for a specified period.Most of the plants set 6 weeks or 2 months as the required post-natal leave; one set it at 4 weeks, one at 4 months, and one at 6 months.Eleven required the amount of post-natal leave to be decided by a physician (the plant physician or the woman's own physician).Extent of Retuirn to Work After Delivery.-Itwas very difficult to find out how many women returned to work after childbirth.Most firms did not keep records of this type.Companies that had been employing women for many years, although they did not keep r-ecords of the number of returns, frequently were able to offer estimates.The textile mills had a very high percentage of returns.Some electrical plants also had a high percentage.Reinistatem1ent and Senziority.-Among the establishments that l4ad high percentages of returns to work the question of reinstate- ment and seniority was probably a factor in motivating an early r-eturn.In several of these plants reinstatement and seniority privileges were effective for only 2 to 3 months after childbirth.If the period in which these privileges were effective were lengthened, wAomen might be inclined to take longer post-natal leave."Some British Statistics An investigation on employment of women in industry before and after childbirth in this country carried out during 1940-2 by the Industrial Welfare Society gives the following general information.Twenty-six firms were approached; they all permit a return to work, but the period after pregnancy varies as follows:At a minimum of 4 weeks 2 firms .. , 5 ,.....
Environmentally relevant xenoestrogen tissue concentrations correlated to biological responses in mice.
Authors: E M Ulrich, A Caperell-Grant, S H Jung, R A Hites, R M Bigsby
Journal: Environmental Health Perspectives (2000)

The effects of xenoestrogens have been extensively studied in rodents, generally under single, high-dose conditions. Using a continuous-release, low-dose system in ovariectomized mice, we correlated the estrogenic end points of uterine epithelial height (UEH) and vaginal epithelial thickness (VET) with concentrations of two organochlorine pesticide isomers in fat and blood. Silastic capsules containing a range of doses of either ss-hexachlorocyclohexane (ss-HCH) or o, p'-dichlorodiphenyltrichloroethane (o,p'-DDT) were implanted subcutaneously, and animals were killed after 1 week. Average blood levels achieved by the various doses were 4.2-620 ng/mL for o,p'-DDT and 5.0-300 ng/mL for ss-HCH. Fat concentrations of o,p'-DDT and ss-HCH correlated linearly to blood levels (o,p'-DDT, r(2) = 0.94; ss-HCH, r(2) = 0.83). Fat concentrations (nanograms per gram of tissue) were higher than blood concentrations (nanograms per milliliter) by 90 +/- 5- and 120 +/- 9-fold (mean +/- SE) for o, p'-DDT and ss-HCH, respectively. The VET ranged from 12 +/- 0.9 microm in controls to 114 +/- 8 microm in treated animals, and was correlated to blood levels of either treatment compound. The UEH ranged from an average of 7.7 +/- 0.3 microm in controls to 26 +/- 2 microm in high-dose o,p'-DDT-treated animals. The UEH was also correlated with ss-HCH concentration, but it plateaued at approximately 11 microm at the highest doses. The lowest blood concentrations that produced statistically significant increases in VET or UEH were 18 +/- 2 ng/mL o,p'-DDT and 42 +/- 4 ng/mL ss-HCH. These values are within the same order of magnitude of blood concentrations found in some human subjects from the general population, suggesting that human blood concentrations of these organochlorines may reach estrogenic levels.
Extensive Intramural Esophageal Hematoma After Transesophageal Echocardiography During Atrial Fibrillation Ablation
Authors: Min-young Kim, Fu Siong Ng, Ben Ariff, George B. Hanna, Zachary Whinnett, Prapa Kanagaratnam, Mark Tanner, Phang Boon Lim
Journal: Circulation (2015)