tbuckley/cabot-search huggingface dataset:
Haemodialysis and haemofiltration on cardiopulmonary bypass.
Authors: M Hakim, D Wheeldon, D W Bethune, B B Milstein, T A English, J Wallwork
Journal: Thorax (1985)

Over a three year period we have used haemodialysis and haemofiltration in parallel with cardiopulmonary bypass in 26 patients. Impaired renal function and excessive fluid retention have been the main indications. Patients on haemodialysis programmes for end stage renal failure did not require further dialysis until at least the third postoperative day, when they could tolerate the haemodynamic disturbance of dialysis. In the other patients these techniques proved valuable in reversing the effects of haemodilution and in controlling the concentration of serum potassium. Our experience has confirmed that haemodialysis and haemofiltration in parallel with cardiopulmonary bypass are useful adjuncts in the perioperative management of patients with impaired renal function undergoing open heart surgery. The techniques are also effective in correcting the fluid retention and biochemical imbalance in patients with congestive cardiac failure, including those with heart transplants.
PADI4 genotype is not associated with rheumatoid arthritis in a large UK Caucasian population
Authors: M. L. Burr, H. Naseem, A. Hinks, S. Eyre, L. J. Gibbons, J. Bowes, A. G. Wilson, J. Maxwell, A. W. Morgan, P. Emery, S. Steer, L. Hocking, D. M. Reid, P. Wordsworth, P. Harrison, W. Thomson, J. Worthington, A. Barton
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Background</h3> Polymorphisms of the peptidylarginine deiminase type 4 (<i>PADI4</i>) gene confer susceptibility to rheumatoid arthritis (RA) in East Asian people. However, studies in European populations have produced conflicting results. This study explored the association of the <i>PADI4</i> genotype with RA in a large UK Caucasian population. <h3>Methods</h3> The PADI4_94 (rs2240340) single nucleotide polymorphism (SNP) was directly genotyped in a cohort of unrelated UK Caucasian patients with RA (n=3732) and population controls (n=3039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was used to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1859) and controls (n=10 599). A further 56 SNPs spanning the <i>PADI4</i> gene were investigated for association with RA using data from the WTCCC study. <h3>Results</h3> The PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all the cases of RA (n=5591) and controls (n=13 638) gave an overall OR of 1.01 (95% CI 0.96 to 1.05, p=0.72). No association with anti-CCP antibodies and no interaction with either shared epitope or <i>PTPN22</i> was detected. No evidence for association with RA was identified for any of the <i>PADI4</i> SNPs investigated. Meta-analysis of previously published studies and our data confirmed no significant association between the PADI4_94 genotype and RA in people of European descent (OR 1.06, 95% CI 0.99 to 1.13, p=0.12). <h3>Conclusion</h3> In the largest study performed to date, the <i>PADI4</i> genotype was not a significant risk factor for RA in people of European ancestry, in contrast to Asian populations.
Bronchoalveolar lavage cellularity in healthy children.
Authors: J Riedler, J Grigg, C Stone, G Tauro, C F Robertson
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The role of bronchoalveolar lavage (BAL) in children remains to be defined, and to date there has been no standardization of acquisition and processing of the BAL fluid. The aim of the present study was to evaluate a standardized protocol for obtaining, processing, and analyzing BAL fluid and to establish reference values for healthy children. Eighteen children 3 mo to 10 yr of age were lavaged with three 1-ml/kg aliquots of normal saline, using a flexible bronchoscope into the right middle lobe. The first aliquot was processed separately; the second and the third were pooled. There was a higher percentage of neutrophils and epithelial cells in the first aliquot. The number of total cells per milliliter (median, Q1 to Q3) in the first aliquot was 60 (45 to 90) x 10(3)/ml; in the pooled sample it was 155 (75 to 257) x 10(3)/ml. Percentages (median, Q1 to Q3) of different cell types in the pooled sample were: macrophages, 91% (84 to 94); lymphocytes, 7.5% (4.7 to 12.8); neutrophils, 1.7% (0.6 to 3.5); eosinophils, 0.15% (0.0 to 0.3). The ratio of helper/cytotoxic T-cells was 0.58 (0.4 to 1). The results of this study demonstrate that BAL, using a standardized protocol adjusting instilled fluid volume by weight, appears to be appropriate in children and that cellular and protein values from healthy children are, apart from differences in lymphocyte subsets, similar to those found in healthy adults.
Deaths certified as asthma and use of medical services: a national case-control study
Authors: P M Sturdy, B K Butland, H R Anderson, J G Ayres, J M Bland, B D W Harrison, C Peckitt, C R Victor
Journal: Thorax (2005)

<b>Background:</b> Studies have linked asthma death to either increased or decreased use of medical services. <b>Methods:</b> A population based case-control study of asthma deaths in 1994–8 was performed in 22 English, six Scottish, and five Welsh health authorities/boards. All 681 subjects who died were under the age of 65 years with asthma in Part I on the death certificates. After exclusions, 532 hospital controls were matched to 532 cases for age, district, and date of asthma admission/death. Data were extracted blind from primary care records. <b>Results:</b> The median age of the subjects who died was 53 years; 60% of cases and 64% of controls were female. There was little difference in outpatient attendance (55% and 55%), hospital admission for asthma (51% and 54%), and median inpatient days (20 days and 15 days) in the previous 5 years. After mutual adjustment and adjustment for sex, using conditional logistic regression, three variables were independently associated with asthma death: fewer general practice contacts (odds ratio 0.82 (95% confidence interval (CI) 0.74 to 0.91) per 5 contacts) in the previous year, more home visits (1.14 (95% CI 1.08 to 1.21) per visit) in the previous year, and fewer peak expiratory flow recordings (0.83 (95% CI 0.74 to 0.92) per occasion) in the previous 3 months. These associations were similar after adjustment for markers of severity, psychosocial factors, systemic steroids, short acting bronchodilators and antibiotics, although the association with peak flow was weakened and just lost significance. <b>Conclusion:</b> Asthma death is associated with less use of primary care services. Both practice and patient factors may be involved and a better understanding of these may offer possibilities for reducing asthma death.
Physiotherapy intervention in Parkinson's disease: systematic review and meta-analysis
Authors: C. L. Tomlinson, S. Patel, C. Meek, C. P. Herd, C. E. Clarke, R. Stowe, L. Shah, C. Sackley, K. H. O. Deane, K. Wheatley, N. Ives
Journal: BMJ (2012)

To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson's disease.
Increased Nuclear Localization of Transcription Factor Y-Box Binding Protein 1 Accompanied by Up-Regulation of P-glycoprotein in Breast Cancer Pretreated with Paclitaxel
Authors: Tomoyuki Fujita, Ken-ichi Ito, Hiroto Izumi, Morihiko Kimura, Muneaki Sano, Hiroshi Nakagomi, Kazuma Maeno, Yoshihisa Hama, Kiyoshi Shingu, Shin-ichi Tsuchiya, Kimitoshi Kohno, Minoru Fujimori
Journal: Clinical Cancer Research (2005)

The Y-box binding protein 1 (YB-1) regulates expression of P-glycoprotein encoded by the MDR1 gene. There have been no previous studies regarding the involvement of YB-1 in the development of resistance to paclitaxel. The present study was done to examine how paclitaxel affects the localization and expression of YB-1 in breast cancer.We evaluated the expression and localization of YB-1 and P-glycoprotein in breast cancer tissues obtained from 27 patients before and after treatment with paclitaxel. The effect of paclitaxel on localization of cellular YB-1 was examined by using GFP-YB-1. Interaction of YB-1 with the Y-box motif of the MDR1 promoters was studied by electrophoretic mobility shift assay. The effects of paclitaxel on MDR1 promoter activity were examined by luciferase assay.Of 27 breast cancer tissues treated with paclitaxel, nine (33%) showed translocation of YB-1 from the cytoplasm to the nucleus together with increased expression of P-glycoprotein during the course of treatment. Twelve breast cancer tissues (44%) showed neither translocation of YB-1 nor increased expression of P-glycoprotein. Nuclear translocation of YB-1 was correlated significantly with increased expression of P-glycoprotein (P=0.0037). Confocal analysis indicated that paclitaxel induced nuclear translocation of green fluorescent fused YB-1 in MCF7 cells. Furthermore, binding of YB-1 to the Y-box of MDR1 promoter was increased in response to treatment with paclitaxel. In addition, MDR1 promoter activity was significantly up-regulated by paclitaxel in MCF7 cells (P<0.001).The results of the present study suggested that YB-1 may be involved in the development of resistance to paclitaxel in breast cancer.
Endothelial Krüppel-Like Factor 4 Mediates the Protective Effect of Statins against Ischemic AKI
Authors: Tadashi Yoshida, Maho Yamashita, Mieko Iwai, Matsuhiko Hayashi
Journal: Journal of the American Society of Nephrology (2015)

Endothelial cells participate in the pathophysiology of ischemic AKI by increasing the expression of cell adhesion molecules and by recruiting inflammatory cells. We previously showed that endothelial Krüppel-like factor 4 (Klf4) regulates vascular cell adhesion molecule 1 (Vcam1) expression and neointimal formation after carotid injury. In this study, we determined whether endothelial Klf4 is involved in ischemic AKI using endothelial Klf4 conditional knockout (Klf4 cKO) mice generated by breeding Tek-Cre mice and Klf4 floxed mice. Klf4 cKO mice were phenotypically normal before surgery. However, after renal ischemia-reperfusion injury, Klf4 cKO mice exhibited elevated serum levels of urea nitrogen and creatinine and aggravated renal histology compared with those of Klf4 floxed controls. Moreover, Klf4 cKO mice exhibited enhanced accumulation of neutrophils and lymphocytes and elevated expression of cell adhesion molecules, including Vcam1 and Icam1, in injured kidneys. Notably, statins ameliorated renal ischemia-reperfusion injury in control mice but not in Klf4 cKO mice. Mechanistic analyses in cultured endothelial cells revealed that statins increased KLF4 expression and that KLF4 mediated the suppressive effect of statins on TNF-α-induced VCAM1 expression by reducing NF-κB binding to the VCAM1 promoter. These results provide evidence that endothelial Klf4 is renoprotective and mediates statin-induced protection against ischemic AKI by regulating the expression of cell adhesion molecules and concomitant recruitment of inflammatory cells.
Migration inhibitory factor up-regulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 via Src, PI3 kinase, and NFκB
Authors: M. Asif Amin, Christian S. Haas, Kui Zhu, Pamela J. Mansfield, Michael J. Kim, Nicholas P. Lackowski, Alisa E. Koch
Journal: Blood (2005)
A Genome Scan for ESRD in Black Families Enriched for Nondiabetic Nephropathy
Authors: Barry I. Freedman, Carl D. Langefeld, Stephen S. Rich, Christopher J. Valis, Miche[Combining Grave Accent]le M. Sale, Adrienne H. Williams, W. Mark Brown, Stephanie R. Beck, Pamela J. Hicks, Donald W. Bowden
Journal: Journal of the American Society of Nephrology (2004)

Nephropathy is a complex disorder, with predisposition influenced by the interplay of both genetic and environmental factors. As part of an effort to map genes that predispose to ESRD, a genome scan was performed in 264 black pedigrees that contained 296 ESRD-affected sibling pairs using multipoint nonparametric linkage analysis methods. The cause of ESRD in index cases was consistent with hypertension-associated ESRD. Nonparametric linkage (NPL) regression provided modest evidence of linkage to 9p21.3 near D9S1121 (logarithm of odds [LOD] = 2.03), 1q25.1 near D1S1589 (LOD = 1.62), and 13q33.3 near D13S796 (LOD = 1.02). Adjusting for the evidence of linkage at the other loci through the NPL regression analysis provided evidence for linkage to 1q25.1, 6p23, and 9p21.3. The NPL regression and ordered subset analyses suggest that the evidence for linkage significantly increased with early onset of ESRD (2q32.1 LOD = 3.89, 13q13.1 LOD = 3.90), increased BMI (8p22 LOD = 3.37, 13q33.3 LOD = 5.20, 18p11.3 LOD = 2.38), early onset of hypertension (14q21.1 LOD = 3.19, 20q13.2 LOD = 2.32), and late onset of hypertension (4q13.1 LOD = 3.44, 5p15.33 LOD = 2.82). Multipoint single-locus linkage analysis provided modest evidence of linkage to nondiabetic ESRD on 9p21.3, 1q25.1 (in the region of the podocin gene), and 13q33.3. NPL regression and ordered subset analyses also identified loci on 13q13.1 and 13q33.3 as contributing to early-onset ESRD and ESRD in the presence of increased BMI, respectively. These regions should receive priority in the search for loci that contribute susceptibility to nondiabetic nephropathy.
A Concurrent Flow Model for Extraction during Transcapillary Passage
Authors: JAMES B. BASSINGTHWAIGHTE
Journal: Circulation Research (1974)

A model for capillary-tissue exchange in a uniformly perfused organ with uniform capillary transit times and no diffusional capillary interactions was designed to permit the exploration of the influences of various parameters on the interpretation of indicator-dilution curves obtained at the venous outflow following the simultaneous injection of tracers into the arterial inflow. These parameters include tissue geometric factors, longitudinal diffusion and volumes of distribution of tracers in blood and tissue, hematocrit, volumes of nonexchanging vessels and the sampling system, capillary permeability, P . capillary surface area, S , and flow of blood- or solute-containing fluid, F' s . An assumption of instantaneous radial diffusion in the extravascular region is appropriate when intercapillary distances are small, as they are in the heart, or permeabilities are low, as they are for lipophobic solutes. Numerical solutions were obtained for dispersed input functions similar to normal intravascular dye-dilution curves. Axial extravascular diffusion showed a negligible influence at low permeabilities. The "instantaneous extraction" of a permeating solute can provide an estimate of PS/F' s , the ratio of the capillary permeability-surface area product to the flow, when PS/F' s lies between approximately 0.05 and 3.0; the limits of the range depend on the extravascular volume of distribution and the influences of intravascular dispersion. The most accurate estimates were obtained when experiments were designed so that PS/F' s was between 0.2 and 1.0 or peak extractions were between 0.1 and 0.6.
CD7 in acute myeloid leukemia: correlation with loss of wild-type CEBPA, consequence of epigenetic regulation
Authors: Sonja Röhrs, Michaela Scherr, Julia Romani, Margarete Zaborski, Hans G Drexler, Hilmar Quentmeier
Journal: Journal of Hematology & Oncology (2010)

CD7 is a negative prognostic marker in myeloid malignancies. In acute myeloid leukemia (AML), an inverse correlation exists between expression of wild-type CEBPA and CD7. Aim of this study was to find out whether C/EBPalpha is a negative regulator of CD7 and which other regulatory mechanisms might be involved.As already described for primary AML cells, the majority of AML cell lines tested were either C/EBPalpha+/CD7- or C/EBPalpha-/CD7+. However, the existence of isolated CD7+ cell lines expressing wild-type C/EBPalpha challenges the notion that C/EBPalpha acts as a unique repressor of CD7. Furthermore, ectopic expression of CEBPA did not reduce CD7 in CD7+ cells and knock-down of C/EBPalpha failed to induce CD7 in CD7- cells. In contrast, the DNA demethylating agent Aza-2'deoxycytidine triggered CD7 expression in CD7- AML and in T-cell lines suggesting epigenetic regulation of CD7. Bisulfite sequencing data confirmed that CpGs in the CD7 exon1 region are methylated in CD7- cell lines, and unmethylated in CD7+ cell lines.We confirmed an inverse correlation between the expression of wild-type CEBPA and of CD7 in AML cells. Our results contradict the hypothesis that C/EBPalpha acts as repressor for CD7, and instead show that epigenetic mechanisms are responsible for CD7 regulation, in AML cells as well as in T-cells, the typical CD7 expressing cell type.
Desferrioxamine attenuates minor lung injury following surgical acute liver failure
Authors: G. G. Kostopanagiotou, K. A. Kalimeris, N. P. Arkadopoulos, A. Pafiti, D. Panagopoulos, V. Smyrniotis, D. Vlahakos, C. Routsi, M. E. Lekka, G. Nakos
Journal: European Respiratory Journal (2008)

Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study was to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF. 14 adult female domestic pigs were subjected to surgical devascularisation of the liver and were randomised to a study group (DFX group, n = 7), which received post-operative intravenous infusion of DFX (14.5 mg·kg −1 ·h −1 for the first 6 h post-operatively and 2.4 mg·kg −1 ·h −1 until completion of 24 h), and a control group (n = 7). Post-operative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis. DFX resulted in reduced BALF protein levels and tissue phospholipase (PL)A 2 activity. Plasma malondialdehyde and BALF nitrate and nitrite concentrations were lower, while catalase activity in the lung was higher after DFX treatment. PLA 2 , platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocyte necrosis and total lung injury in the DFX-treated animals. DFX reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA 2 and the attenuation of pneumonocyte necrosis could represent beneficial mechanisms by which DFX improves alveolar–capillary membrane permeability and prevents alveolar space collapse.
Intergenerational transfers and the cost of allomothering in traditional societies
Authors: Karen L. Kramer
Journal: Behavioral and Brain Sciences (2010)

Abstract The question of why helpers help is debated in the cooperative breeding literature. Recent reevaluations of inclusive fitness theory have important implications for traditional populations in which the provisioning of young occurs in the context of intergenerational transfers. These transfers link older and younger generations in an economic relationship that both minimizes the demand for help and the cost of helping.
Molecular and Cellular Aspects of Calcific Aortic Valve Disease
Authors: Dwight A. Towler
Journal: Circulation Research (2013)

Calcific aortic valve disease (CAVD) increasingly afflicts our aging population. One third of our elderly have echocardiographic or radiological evidence of calcific aortic valve sclerosis, an early and subclinical form of CAVD. Age, sex, tobacco use, hypercholesterolemia, hypertension, and type II diabetes mellitus all contribute to the risk of disease that has worldwide distribution. On progression to its most severe form, calcific aortic stenosis, CAVD becomes debilitating and devastating, and 2% of individuals &gt;60 years are affected by calcific aortic stenosis to the extent that surgical intervention is required. No effective pharmacotherapies exist for treating those at risk for clinical progression. It is becoming increasingly apparent that a diverse spectrum of cellular and molecular mechanisms converge to regulate valvular calcium load; this is evidenced not only in histopathologic heterogeneity of CAVD, but also from the multiplicity of cell types that can participate in valve biomineralization. In this review, we highlight our current understanding of CAVD disease biology, emphasizing molecular and cellular aspects of its regulation. We end by pointing to important biological and clinical questions that must be answered to enable sophisticated disease staging and the development of new strategies to treat CAVD medically.
Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil With Bevacizumab in Patients With Metastatic Gastroesophageal Adenocarcinoma
Authors: Manish A. Shah, Minaxi Jhawer, David H. Ilson, Robert A. Lefkowitz, Edric Robinson, Marinela Capanu, David P. Kelsen
Journal: Journal of Clinical Oncology (2010)

To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies.Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m², fluorouracil 400 mg/m², leucovorin 400 mg/m² on day 1, fluorouracil 1,000 mg/m²/d × 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m² on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates.In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%).mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively.