tbuckley/cabot-search huggingface dataset:
Role of Megalin in Endocytosis of Advanced Glycation End Products
Authors: Akihiko Saito, Ryoji Nagai, Atsuhito Tanuma, Hitomi Hama, Kenji Cho, Tetsuro Takeda, Yutaka Yoshida, Tosifusa Toda, Fujio Shimizu, Seikoh Horiuchi, Fumitake Gejyo
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Advanced glycation end products (AGE) are filtered by glomeruli and reabsorbed and metabolized by proximal tubule cells (PTC). In renal failure, decreased renal AGE metabolism likely accounts for the accumulation in serum that is related to uremic complications. In diabetes, AGE generation is increased, and the handling mechanisms in PTC are likely associated with the pathogenesis of tubulointerstitial injury. It is therefore important to clarify the mechanisms of the AGE metabolism to develop a strategy for removing AGE in uremia and to elucidate the pathogenesis of diabetic nephropathy. To this end, this study focused on the molecular analysis of megalin, a multi-ligand endocytic receptor, in PTC. AGE uptake analysis was performed using the rat yolk sac-derived L2 cell line system established for the analysis of megalin's endocytic functions. The cells mediated specific internalization and degradation of AGE, which were significantly blocked by anti-megalin IgG, indicating that megalin is involved in the cellular processes. However, cell surface AGE-binding assays and ligand blot analysis revealed no evidence that megalin is a direct AGE receptor. Affinity chromatography and ligand blot analysis originally revealed that 200-kD and 400-kD proteins in the cells bind to AGE and the 200-kD protein to megalin in a Ca2+-dependent manner. The binding of megalin with the 200-kD protein was suppressed by receptor-associated protein (RAP), a ligand for megalin. In conclusion, megalin functions for endocytosis of AGE via an indirect mechanism. L2 cells express novel AGE-binding proteins, one of which may interact with megalin. E-mail: [email protected]
Nurse-led care in dermatology: a review of the literature
Authors: M. Courtenay, N. Carey
Journal: British Journal of Dermatology (2005)

Background Nurses play lead roles in the delivery of care in dermatology. While a number of primary studies have been conducted evaluating nurse‐led care in dermatology, review and synthesis of the findings from these studies has not been undertaken. Objectives To systematically identify, summarize and critically appraise the current evidence regarding the impact and effectiveness of nurse‐led care in dermatology. Methods Systematic searches were done of CINAHL, MEDLINE, British Nursing Index and the Royal College of Nursing Library Catalogue from 1990 until March 2005. The searches were not restricted to the U.K., and were supplemented by an extensive hand search of the literature through references identified from retrieved articles and by contact with experts in the field. Results A total of 14 relevant publications were identified (and included findings from both primary and secondary care), of which five were descriptions of nursing activities, five were evaluations of nurse interventions and four were patient evaluations of nurse‐led care. The evidence emerging from the literature indicates that nurses are treating a number of dermatological conditions, primarily using treatment protocols, across a broad range of clinical settings. However, there is a lack of confidence among nurses working in primary care (predominantly practice nurses) to treat some of these conditions (including scalp scaling in psoriasis and infected eczema). Although the importance of education is recognized, the educational needs of these nurses are frequently unmet. The benefits of nurse interventions on service delivery include a reduction in the severity of condition and more effective use of topical therapies. Patients report faster access to treatment, a reduction in referrals to the GP or dermatologist, and an increase in knowledge of their condition. Conclusions Nurses frequently play lead roles in the diverse range of models of care that exist in dermatology. Although findings of the review are generally positive, there are methodological weaknesses and under‐researched issues, e.g. cost effectiveness of nurse‐led care, and extended independent and supplementary nurse prescribing in dermatology, that point to the need for further rigorous evaluation.
Primary Intravitreal Bevacizumab for Diffuse Diabetic Macular Edema
Authors: J. Fernando Arevalo, Juan G. Sanchez, Lihteh Wu, Mauricio Maia, Arturo A. Alezzandrini, Miguel Brito, Sergio Bonafonte, Silvio Lujan, Manuel Diaz-Llopis, Natalia Restrepo, Francisco J. Rodríguez, Patricia Udaondo-Mirete
Journal: Ophthalmology (2009)
The relationship of cardiorespiratory fitness with some of the anthropometry characteristic and physical activity in girls and boys 8-12 years old
Authors: Kazemi Nasibeh
Journal: British Journal of Sports Medicine (2010)

Background Physical activity (PA) participation is associated with health benefits and/or health risks. Low cardiorespiratory fitness (CVF) and fatness seem to be important health problems. Regarding some of the studies, it has been proven that CVF is related to daily PA and fatness. Objective The purpose of this study was evaluating the relationship between CVF with some of the anthropometric characteristics and PA in children aged 8–12 years. Design A cross-sectional study of 44 children aged (mean±SD) 9.73±1.38 years, height 134.5±11.77 cm and weight 32.04±8.66 kg from Noorabad city volunteered for this study. Before performance of any testing, the enrolled children's parents provided written informed consent and all children filled up an informed consent form. The current health status of the children was checked, CVF was measured by Bruce's treadmill test and the recording paper of daily PA for 2 days of a week (a holiday and a non-holiday) was filled by the children's parents. Body mass index (BMI) was calculated as weight/height squared (kg/m 2 ), and using Jackson's formula the body fat percentage (BF%) was calculated. Pearson bivariate correlation analysis was done. The analysis was performed using SPSS (version 15.0), and the level of significance was set at p=0.5. Results A statistically significant relationship was found between CVF (VO 2 max) and PA (p=0.0005), BMI (0.034) and BF% (p=0.005). Suggestion Our cross-sectional results suggest that PA may improve children's CVF. In addition, we can estimate by VO 2 max measuring BMI and BF%.
STUDY DESIGN FOR CLINICAL EVALUATION OF PHENOTHIAZINE DERIVATIVES
Authors: H. H. PEPPEL, T. JOYNES
Journal: American Journal of Psychiatry (1963)

A short clinical screen was devised for quickly assessing the value of new phenothiazine compounds in treating schizophrenia. The 3-month controlled trial utilizing chlorpromazine as the standard, embraces only patients stubbornly resistant to treatment, and employs a special rating scale to differentiate among the various common drug actions. Carphenazine maleate was the first drug tested. It was found to be superior to chlorpromazine in ability to influence mood, physical and mental activity, degree of hostility and tension. It is recommended for use in chronic schizophrenia when other therapies fail.
Hundreds of putatively functional small open reading frames in Drosophila
Authors: Emmanuel Ladoukakis, Vini Pereira, Emile G Magny, Adam Eyre-Walker, Juan Pablo Couso
Journal: Genome biology (2011)

Abstract Background The relationship between DNA sequence and encoded information is still an unsolved puzzle. The number of protein-coding genes in higher eukaryotes identified by genome projects is lower than was expected, while a considerable amount of putatively non-coding transcription has been detected. Functional small open reading frames (smORFs) are known to exist in several organisms. However, coding sequence detection methods are biased against detecting such very short open reading frames. Thus, a substantial number of non-canonical coding regions encoding short peptides might await characterization. Results Using bio-informatics methods, we have searched for smORFs of less than 100 amino acids in the putatively non-coding euchromatic DNA of Drosophila melanogaster , and initially identified nearly 600,000 of them. We have studied the pattern of conservation of these smORFs as coding entities between D. melanogaster and Drosophila pseudoobscura , their presence in syntenic and in transcribed regions of the genome, and their ratio of conservative versus non-conservative nucleotide changes. For negative controls, we compared the results with those obtained using random short sequences, while a positive control was provided by smORFs validated by proteomics data. Conclusions The combination of these analyses led us to postulate the existence of at least 401 functional smORFs in Drosophila , with the possibility that as many as 4,561 such functional smORFs may exist.
Striatal Activity Underlies Novelty-Based Choice in Humans
Authors: Bianca C. Wittmann, Nathaniel D. Daw, Ben Seymour, Raymond J. Dolan
Journal: Neuron (2008)

The desire to seek new and unfamiliar experiences is a fundamental behavioral tendency in humans and other species.In economic decision making, novelty seeking is often rational, insofar as uncertain options may prove valuable and advantageous in the long run.Here, we show that, even when the degree of perceptual familiarity of an option is unrelated to choice outcome, novelty nevertheless drives choice behavior.Using functional magnetic resonance imaging (fMRI), we show that this behavior is specifically associated with striatal activity, in a manner consistent with computational accounts of decision making under uncertainty.Furthermore, this activity predicts interindividual differences in susceptibility to novelty.These data indicate that the brain uses perceptual novelty to approximate choice uncertainty in decision making, which in certain contexts gives rise to a newly identified and quantifiable source of human irrationality.
Alloreactive and H-2-restricted Lyt 23 cytotoxic T lymphocytes derive from a common pool of antecedent Lyt 123 precursors.
Authors: C Hardt, K Pfizenmaier, M Röllinghoff, J Klein, H Wagner
Journal: The Journal of Experimental Medicine (1980)

If the collaborative requirement of Lyt 1 T helper cells is bypassed by the Lyt 1 T cell-derived mediator of T help, termed Il-2, upon antigenic stimulation, PNA+ Lyt 123 thymocytes differentiate into either alloreactive or H-2-restricted PNA- Lyt 23 cytotoxic effector cells. Along the differentiation pathway from Lyt 123 leads to 23 effector cells, cytolytic activity is carried out by T cells that still express the Lyt 123 phenotype. The data establish that Lyt 23 CTL are produced by differentiation from antecedent Lyt 123 cells.
PCV and/or TMZ chemotherapy in 255 gliomas. Analysis of the clinical experience from a neuro-oncology data-base
Authors: A. Pace, A. Pompili, M. Maschio, E. Galie', S. Telera, B. Jandolo, E. Occhipinti, C. M. Carapella
Journal: Journal of Clinical Oncology (2004)

1538 Background: The role of chemotherapy (CT) in the treatment of malignant gliomas is still debated. Different chemotherapeutic agents are currently used with modest impact on survival. At the moment there are no clear-cut data indicating more effective or better-tolerated treatments. Furthermore the evaluation of response to CT should include also clinical benefit and quality of life. Methods: We retrospectively analyzed our experience in chemotherapy of malignant gliomas with the aim of evaluating time to tumor progression, clinical benefit, quality of life (EORTC QLQ-C30), and toxicity. Results: 255 recurrent malignant glioma patients were treated with chemotherapy (PCV or Temozolomide) in our Institution since 1997. Histology was: Glioblastoma (GB) in 123; Anaplastic astrocytoma (AA) 56; Mixed Anaplastic Oligo-Astrocytoma (AO) 43; Progressive Low Grade Astrocytoma (LGA) 42; Anaplastic Oligos (O) 28. The overall response rate (RR) by histology was: CR+PR in GB 7.4%; AA 26.8%; AO 51.6%; LGA 48.4%; O 44.4%. Treatment schedule was PCV in 193 patients and Temozolomide (TMZ) standard schedule in 129. RR was not significant different for the two treatments. 69 patients received two line of chemotherapy (44 first line PCV and 25 first line TMZ). In the present series, tumors which respond at first line CT are more likely to respond to second line treatment. In 13.5% patients treated with PCV the treatment was interrupted for toxicity. During TMZ treatment 10.9% of patients presented myelotoxicity grade 3–4 (WHO), leading to treatment interruption in 4.6% of cases. Conclusions: Considering the modest influence of CT on overall survival in malignant gliomas, less toxic drugs should be preferred for first line treatment. No significant financial relationships to disclose.
Mechanism of the negative inotropic action of leukotrienes C4 and D4 on isolated rat heart
Authors: J. A BITTL, M. A PFEFFER, R. A LEWIS, M. M MEHROTRA, E J COREY, K F. AUSTEN
Journal: Cardiovascular Research (1985)

Leukotrienes C4 and D4 (LTC4 and LTD4), possible mediators of cardiac dysfunction during inflammatory injury, may depress cardiac function by reducing coronary flow or by exerting a negative effect directly on the myocardium. We used an isovolumic rat heart preparation perfused at constant pressure and measured left ventricular developed pressure (mmHg), coronary flow (ml·min−1), oxygen extraction, and myocardial oxygen consumption and delivery (μmol O2·l gramme dry weight l−1·min−1) during infusion of five doses of angiotensin II, LTC4, LTD4 (∼10 to ∼300 pmol·min−1). and noradrenaline (400 to 2000 pmol·min−1), or perfusion with medium which contained calcium at half-concentration. LTC4 and LTD4 were equipotent with angiotensin. At low effective doses, increased oxygen extraction offset the decrease in oxygen delivery, maintaining a stable level of oxygen consumption and left ventricular developed pressure. At the highest doses, angiotensin, LTC4 and LTD4 reduced coronary flow from 21 to 15, 21 to 13, and 21 to 13 ml·min−1, respectively. And, despite greater oxygen extraction of 59%, 58% and 65% for angiotensin, LTC4 and LTD4, left ventricular developed pressure fell from a baseline of 120 mmHg to 113, 106 and 92, respectively. In contrast, low calcium perfusion reduced left ventricular developed pressure (126 to 92) and oxygen extraction (46 to 30%) without changing coronary flow or oxygen delivery. These results suggest that LTC4 and LTD4 are potent coronary vasoconstricting agents which depress cardiac function by limiting oxygen delivery.
Metabolism of plasminogen in healthy subjects: effect of tranexamic acid
Authors: D. Collen, G. Tytgat, H. Claeys, M. Verstraete, P. Wallén
Journal: Journal of Clinical Investigation (1972)

The metabolism of human plasminogen labeled with radioactive iodine was studied in 12 healthy men. The labeled plasminogen had a high specific activity and the same elution on Sephadex G-100 as the plasminogen activity in plasma. Immunoelectrophoresis revealed a single precipitin line. Polyacrylamide gel electrophoresis revealed six main bands, all with plasminogen properties and radioactivity. The purified plasminogen behaved as a homogeneous protein in the turnover experiments. The plasma radioactivity data were adequately approximated by a sum of two exponential terms. The metabolism of plasminogen was therefore represented by a two-compartment mammillary model.
Characteristics of Physical Activities in Daily Life in Chronic Obstructive Pulmonary Disease
Authors: Fabio Pitta, Thierry Troosters, Martijn A. Spruit, Vanessa S. Probst, Marc Decramer, Rik Gosselink
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Quantification of physical activities in daily life in patients with chronic obstructive pulmonary disease has increasing clinical interest. However, detailed comparison with healthy subjects is not available. Furthermore, it is unknown whether time spent actively during daily life is related to lung function, muscle force, or maximal and functional exercise capacity. We assessed physical activities and movement intensity with the DynaPort activity monitor in 50 patients (age 64 ± 7 years; FEV1 43 ± 18% predicted) and 25 healthy elderly individuals (age 66 ± 5 years). Patients showed lower walking time (44 ± 26 vs. 81 ± 26 minutes/day), standing time (191 ± 99 vs. 295 ± 109 minutes/day), and movement intensity during walking (1.8 ± 0.3 vs. 2.4 ± 0.5 m/second2; p < 0.0001 for all), as well as higher sitting time (374 ± 139 vs. 306 ± 108 minutes/day; p = 0.04) and lying time (87 ± 97 vs. 29 ± 33 minutes/day; p = 0.004). Walking time was highly correlated with the 6-minute walking test (r = 0.76, p < 0.0001) and more modestly to maximal exercise capacity, lung function, and muscle force (0.28 < r < 0.64, p < 0.05). Patients with chronic obstructive pulmonary disease are markedly inactive in daily life. Functional exercise capacity is the strongest correlate of physical activities in daily life.
IgD Heavy-Chain Deposition Disease
Authors: Virginie Royal, Patrick Quint, Martine Leblanc, Richard LeBlanc, Garrett F. Duncanson, Robert L. Perrizo, Fernando C. Fervenza, Paul Kurtin, Sanjeev Sethi
Journal: Journal of the American Society of Nephrology (2014)

Monoclonal Ig deposition disease (MIDD) is a rare complication of monoclonal gammopathy characterized by deposition of monoclonal Ig light chains and/or heavy chains along the glomerular and tubular basement membranes. Here, we describe a unique case of IgD deposition disease. IgD deposition is difficult to diagnose, because routine immunofluorescence does not detect IgD. A 77-year-old man presented with proteinuria and renal failure, and kidney biopsy analysis showed a nodular sclerosing GN with extensive focal global glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Immunofluorescence was negative for Ig deposits, although electron microscopy showed deposits in the glomeruli and along tubular basement membranes. Laser microdissection of glomeruli and mass spectrometry of extracted peptides showed a large spectra number for IgD, and immunohistochemistry showed intense glomerular and tubular staining for IgD. Together, these findings are consistent with IgD deposition disease. Bone marrow biopsy analysis showed 5% plasma cells, which stained for IgD. The patient was treated with bortezomib and dexamethasone, which resulted in improvement of hematologic parameters but no improvement of renal function. The diagnosis of IgD deposition disease underscores the value of laser microdissection and mass spectrometry in further evaluating renal biopsies when routine assessment fails to reach an accurate diagnosis.
The Role of Protein Kinase CK2 in Glioblastoma Development
Authors: Haitao Ji, Zhimin Lu
Journal: Clinical Cancer Research (2013)

Abstract Glioblastoma is the most prevalent and malignant primary brain tumor in adults, and its response to current therapies is limited. Protein kinase CK2 is overexpressed in glioblastoma and regulates glioblastoma cell survival, proliferation, and migration and brain tumorigenesis. Targeting CK2 for glioblastoma treatment may benefit patients with glioblastoma. Clin Cancer Res; 19(23); 6335–7. ©2013 AACR.
Race Differences in Long-Term Diabetes Management in an HMO
Authors: Alyce S. Adams, Fang Zhang, Connie Mah, Richard W. Grant, Ken Kleinman, James B. Meigs, Dennis Ross-Degnan
Journal: Diabetes Care (2005)

OBJECTIVE—We examined race differences in diabetes outcomes over 4–8 years in a single HMO. RESEARCH DESIGN AND METHODS—We identified black and white adult diabetic patients who were continuously enrolled (1992–2001) and in whom diabetes was 1) diagnosed before 1994 (n = 1,686) or 2) newly diagnosed in 1994–1997 (n = 1,280). We used hierarchical models to estimate the effect of race on average annual HbA1c (A1C) controlling for baseline A1C, BMI, and age, as well as annual measures of type of diabetes medications, diabetes-related hospitalization, time and the number of A1C tests, physician visits, and nondiabetes medications. Stratifying by sex accounted for significant interactions between sex and race. RESULTS—At baseline, black and white patients had similar rates of A1C testing and physician visits, but blacks had higher unadjusted A1C values. In multivariate models, among patients with previously diagnosed diabetes, average A1C was nonsignificantly 0.11 higher (95% CI −0.12 to 0.34) in black than in white men but was 0.30 higher (0.14–0.46; P = 0.0007) in black than in white women. Among patients with newly diagnosed diabetes, the adjusted black-white gap was 0.49 among men (0.17–0.80; P = 0.007) and was 0.05 among women (−0.20 to –0.31), which was positive but not significant. CONCLUSIONS—Factors other than the quality of care may explain persistent race differences in A1C in this setting. Future interventions should target normalization of A1C by identifying potential psychosocial barriers to therapy intensification among patients and clinicians and development of culturally appropriate interventions to aid patients in successful self-management.
Polysaccharide‐Coated PCL Nanofibers for Wound Dressing Applications
Authors: Florence Croisier, Ganka Atanasova, Yves Poumay, Christine Jérôme
Journal: Advanced Healthcare Materials (2014)

Polysaccharide‐based nanofibers with a multilayered structure are prepared by combining electrospinning (ESP) and layer‐by‐layer (LBL) deposition techniques. Charged nanofibers are firstly prepared by electrospinning poly(ε‐caprolactone) (PCL) with a block‐copolymer bearing carboxylic acid functions. After deprotonation of the acid groups, the layer‐by‐layer deposition of polyelectrolyte polysaccharides, notably chitosan and hyaluronic acid, is used to coat the electrospun fibers. A multilayered structure is achieved by alternating the deposition of the positively charged chitosan with the deposition of a negatively charged polyelectrolyte. The construction of this multilayered structure is followed by Zeta potential measurements, and confirmed by observation of hollow nanofibers resulting from the dissolution of the PCL core in a selective solvent. These novel polysaccharide‐coated PCL fiber mats remarkably combine the mechanical resistance typical of the core material (PCL)—particularly in the hydrated state—with the surface properties of chitosan. The control of the nanofiber structure offered by the electrospinning technology, makes the developed process very promising to precisely design biomaterials for tissue engineering. Preliminary cell culture tests corroborate the potential use of such system in wound healing applications.
Increasing paediatric empyema admissions
Authors: R Gupta
Journal: Thorax (2006)

Increasing paediatric empyema admissionsEmpyema is most often a complication of bacterial pneumonia or, less commonly, thoracic trauma or surgery.There have been reports of increasing numbers of children presenting to regional units in the UK, 1-3 but there are no published national data that may provide evidence of a clear trend.Analysis of national routine admissions data provides information on health service utilisation and may provide a marker for the incidence of this relatively uncommon disease.Hospital admissions in England were obtained from the hospital episode statistics system (www.dh.gov.uk).This database contains personal, administrative, and medical data on all patients admitted to NHS hospitals in England.It records episodes of care following admission to hospital and assigns a primary diagnosis on discharge using the WHO International Classification of Diseases (ICD).Data are available by financial year (1 April to 31 March).From April 1995 diagnoses were classified using the 10th revision of ICD (ICD 10).We identified admissions with a primary diagnosis of pyothorax (which includes the diagnoses of empyema, pyopneumothorax (pneumoempyema) and abscess of the pleura or thorax) in ICD 10 (code J86) between April 1995 and March 2003.