tbuckley/cabot-search huggingface dataset:
Longitudinal membrane function in functionally anuric patients treated with APD: Data from EAPOS on the effects of glucose and icodextrin prescription
Authors: Simon J. Davies, Edwina A. Brown, Niels E. Frandsen, Anabela S. Rodrigues, Ana Rodriguez-Carmona, Andreas Vychytil, Evelyne Macnamara, Agneta Ekstrand, Anders Tranaeus, Jose C. Divino Filho
Journal: Kidney International (2005)
<i>TP53</i> Mutations in Low-Risk Myelodysplastic Syndromes With del(5q) Predict Disease Progression
Authors: Martin Jädersten, Leonie Saft, Alexander Smith, Austin Kulasekararaj, Sabine Pomplun, Gudrun Göhring, Anette Hedlund, Robert Hast, Brigitte Schlegelberger, Anna Porwit, Eva Hellström-Lindberg, Ghulam J. Mufti
Journal: Journal of Clinical Oncology (2011)

To determine the frequency of TP53 mutations and the level of p53 protein expression by immunohistochemistry (IHC) in low-risk myelodysplastic syndromes (MDS) with del(5q) and to assess their impact on disease progression.Pre- and postprogression bone marrow (BM) samples from 55 consecutive patients with International Prognostic Scoring System low risk (n = 32) or intermediate-1 risk (n = 23) were studied by next-generation sequencing of TP53. IHC for p53 was performed on 148 sequential BM samples.TP53 mutations with a median clone size of 11% (range, 1% to 54%) were detected in 10 patients (18%) already at an early phase of the disease. Mutations were equally common in low-risk and intermediate-1-risk patients and were associated with evolution to acute myeloid leukemia (5 of 10 v 7 of 45; P = .045). Nine of 10 patients carrying mutations showed more than 2% BM progenitors with strong p53 staining. The probability of a complete cytogenetic response to lenalidomide was lower in mutated patients (0 of 7 v 12 of 24; P = .024).By using sensitive deep-sequencing technology, we demonstrated that TP53 mutated populations may occur at an early disease stage in almost a fifth of low-risk MDS patients with del(5q). Importantly, mutations were present years before disease progression and were associated with an increased risk of leukemic evolution. TP53 mutations could not be predicted by common clinical features but were associated with p53 overexpression. Our findings indicate a previously unrecognized heterogeneity of the disease which may significantly affect clinical decision making.
Molecular Approaches to Urea Transporters
Authors: Jeff M. Sands
Journal: Journal of the American Society of Nephrology (2002)

Urea plays a critical role in the urine-concentrating mechanism in the inner medulla. Physiologic data provided evidence that urea transport in red blood cells and kidney inner medulla was mediated by specific urea transporter proteins. Molecular approaches during the past decade resulted in the cloning of two gene families for facilitated urea transporters, UT-A and UT-B, encoding several urea transporter cDNA isoforms in humans, rodents, and several nonmammalian species. Polyclonal antibodies have been generated to the cloned urea transporter proteins, and the use of these antibodies in integrative animal studies has resulted in several novel findings, including: (1) the surprising finding that UT-A1 protein abundance and urea transport are increased in the inner medulla during conditions in which urine concentrating ability is reduced; (2) vasopressin increases UT-A1 phosphorylation in rat inner medullary collecting duct; (3) UT-A protein abundance is upregulated in uremia in both liver and heart; and (4) UT-B is expressed in many nonrenal tissues and endothelial cells. This review will summarize the knowledge gained from using molecular approaches to perform integrative studies into urea transporter protein regulation, both in normal animals and in animal models of human diseases, including studies of uremic rats in which urea transporter protein is upregulated in liver and heart.
Bloody diarrhoea in a 54-year-old Arab patient
Authors: H Seidl, T Helmberger, T Schmidt, W Heitland, W Schepp
Journal: Gut (2009)

A 54-year-old Arab patient was referred to our hospital with a 3 week history of bloody diarrhoea, bloating and left-sided abdominal pain, refractory to a 2 week course of ciprofloxacine and metronidazole. The medical history was unremarkable with respect to gastroenterointestinal or thromboembolic diseases. The patient mentioned a daily intake, for the …
Misfolded proteinase K–resistant hyperphosphorylated α-synuclein in aged transgenic mice with locomotor deterioration and in human α-synucleinopathies
Authors: Manuela Neumann, Philipp J. Kahle, Benoit I. Giasson, Laurence Ozmen, Edilio Borroni, Will Spooren, Veronika Müller, Sabine Odoy, Hideo Fujiwara, Masato Hasegawa, Takeshi Iwatsubo, John Q. Trojanowski, Hans A. Kretzschmar, Christian Haass
Journal: Journal of Clinical Investigation (2002)

The pathological modifications of α-synuclein (αS) in Parkinson disease and related diseases are poorly understood. We have detected misfolded αS in situ based on the proteinase K resistance (PK resistance) of αS fibrils, and using specific antibodies against S129-phosphorylated αS as well as oxidized αS. Unexpectedly massive neuritic pathology was found in affected human brain regions, in addition to classical αS pathology. PK resistance and abnormal phosphorylation of αS developed with increasing age in (Thy1)-h[A30P] αS transgenic mice, concomitant with formation of argyrophilic, thioflavin S-positive, and electron-dense inclusions that were occasionally ubiquitinated. αS pathology in the transgenic mice was predominantly in the brainstem and spinal cord. Astrogliosis was found in these heavily affected tissues. Homozygous mice showed the same pathology approximately one year earlier. The transgenic mice showed a progressive deterioration of locomotor function.
Detection of Chromosomal Alterations in the Circulation of Cancer Patients with Whole-Genome Sequencing
Authors: Rebecca J. Leary, Mark Sausen, Isaac Kinde, Nickolas Papadopoulos, John D. Carpten, David Craig, Joyce O’Shaughnessy, Kenneth W. Kinzler, Giovanni Parmigiani, Bert Vogelstein, Luis A. Diaz, Victor E. Velculescu
Journal: Science Translational Medicine (2012)

Clinical management of cancer patients could be improved through the development of noninvasive approaches for the detection of incipient, residual, and recurrent tumors. We describe an approach to directly identify tumor-derived chromosomal alterations through analysis of circulating cell-free DNA from cancer patients. Whole-genome analyses of DNA from the plasma of 10 colorectal and breast cancer patients and 10 healthy individuals with massively parallel sequencing identified, in all patients, structural alterations that were not present in plasma DNA from healthy subjects. Detected alterations comprised chromosomal copy number changes and rearrangements, including amplification of cancer driver genes such as ERBB2 and CDK6. The level of circulating tumor DNA in the cancer patients ranged from 1.4 to 47.9%. The sensitivity and specificity of this approach are dependent on the amount of sequence data obtained and are derived from the fact that most cancers harbor multiple chromosomal alterations, each of which is unlikely to be present in normal cells. Given that chromosomal abnormalities are present in nearly all human cancers, this approach represents a useful method for the noninvasive detection of human tumors that is not dependent on the availability of tumor biopsies.
Should we give long-term macrolide therapy for COPD?
Authors: Philip A J Crosbie, Mark Woodhead
Journal: Thorax (2013)

We would like to take this opportunity to respond to the invitation from the editors of Thorax to engage in a debate over the current place of macrolide therapy in patients with chronic obstructive pulmonary disease (COPD). We believe that the optimism imparted by Albert et al 1 may hide harmful effects that outweigh the currently perceived benefits. In this placebo-controlled, parallel group (but not double-blind) randomised trial, one-quarter of screened patients were excluded from study entry. The main reason for exclusion was the presence of ‘cardiac issues’ related to the known potential of macrolides …
MEF2 Activates a Genetic Program Promoting Chamber Dilation and Contractile Dysfunction in Calcineurin-Induced Heart Failure
Authors: Ralph J. van Oort, Eva van Rooij, Meriem Bourajjaj, Joost Schimmel, Maurits A. Jansen, Roel van der Nagel, Pieter A. Doevendans, Michael D. Schneider, Cees J.A. van Echteld, Leon J. De Windt
Journal: Circulation (2006)

Hypertrophic growth, a risk factor for mortality in heart disease, is driven by reprogramming of cardiac gene expression. Although the transcription factor myocyte enhancer factor-2 (MEF2) is a common end point for several hypertrophic pathways, its precise cardiac gene targets and function in cardiac remodeling remain to be elucidated.We report the existence of synergistic interactions between the nuclear factor of activated T cells and MEF2 transcription factors triggered by calcineurin signaling. To circumvent the embryonic lethality and mitochondrial deficiency associated with germ-line null mutations for MEF2C and MEF2A respectively, we used conditional transgenesis to express a dominant-negative form of MEF2 in the murine postnatal heart and combined this with magnetic resonance imaging to assess MEF2 transcriptional function in Ca2+/calcineurin-induced cardiac remodeling. Surprisingly, end-diastolic and end-systolic ventricular dimensions and contractility were normalized in the presence of severely hypertrophied left ventricular walls on MEF2 inhibition in calcineurin transgenic mice. In line, we generated lines of transgenic mice expressing MEF2A in the heart, which displayed primarily chamber dilation. Microarray profiling indicated that MEF2 promotes a gene profile functioning primarily to or at the nucleus, cytoskeletal and microtubular networks, and mitochondria.These findings assign a novel function to MEF2 transcription factors in the postnatal heart, where they activate a genetic program that minimally affects cardiac growth yet promotes chamber dilation, mechanical dysfunction, and dilated cardiomyopathy.
Nonrandom Distribution of Aberrant Promoter Methylation of Cancer-Related Genes in Sporadic Breast Tumors
Authors: Paola Parrella, Maria Luana Poeta, Antonietta Pia Gallo, Maria Prencipe, Marina Scintu, Adolfo Apicella, Raffaele Rossiello, Giuseppina Liguoro, Davide Seripa, Carolina Gravina, Carla Rabitti, Monica Rinaldi, Theresa Nicol, Stefania Tommasi, Angelo Paradiso, Francesco Schittulli, Vittorio Altomare, Vito Michele Fazio
Journal: Clinical Cancer Research (2004)

Abstract Purpose: In an effort to additionally determine the global patterns of CpG island hypermethylation in sporadic breast cancer, we searched for aberrant promoter methylation at 10 gene loci in 54 primary breast cancer and 10 breast benign lesions. Experimental Design: Genomic DNA sodium bisulfate converted from benign and malignant tissues was used as template in methyl-specific PCR for BRCA1, p16, ESR1, GSTP1, TRβ1, RARβ2, HIC1, APC, CCND2, and CDH1 genes. Results: The majority of the breast cancer (85%) showed aberrant methylation in at least 1 of the loci tested with half of them displaying 3 or more methylated genes. The highest frequency of aberrant promoter methylation was found for HIC1 (48%) followed by ESR1 (46%), and CDH1 (39%). Similar methylation frequencies were detected for breast benign lesions with the exception of the CDH1 gene (P = 0.02). The analysis of methylation distribution indicates a statistically significant association between methylation of the ESR1 promoter, and methylation at CDH1, TRβ1, GSTP1, and CCND2 loci (P &amp;lt; 0.03). Methylated status of the BRCA1 promoter was inversely correlated with methylation at the RARβ2 locus (P &amp;lt; 0.03). Conclusions: Our results suggest a nonrandom distribution for promoter hypermethylation in sporadic breast cancer, with tumor subsets characterized by aberrant methylation of specific cancer-related genes. These breast cancer subgroups may represent separate biological entities with potential differences in sensitivity to therapy, occurrence of metastasis, and overall prognosis.
Building Bridges Between Populations and Samples in Epidemiological Studies
Authors: W. Kalsbeek, G. Heiss
Journal: Annual Review of Public Health (2000)

▪ Abstract The increased use of rigorous population-sampling methods and the analysis of data from those samples in cross-sectional surveys, case-control studies, longitudinal-cohort investigations, and other epidemiological research efforts have raised important statistical issues for health analysts. We describe the origin, implications, and some plausible resolutions for several of these issues. Some of the main issues we consider include (a) establishing whom the sample represents; (b) using sample weights; (c) understanding the role of other important features, such as the use of sampling stratification and the selection of clustered groups of population members; and (d) finding ways to analyze study data with key sampling features in mind. Ultimately, resolution of all of these issues requires that analysts clearly define a reference population and then understand the role of design features in relating sample results to that population.
Meditation: a modulator of the immune response to physical stress? A brief report.
Authors: E E Solberg, R Halvorsen, J Sundgot-Borgen, F Ingjer, A Holen
Journal: British Journal of Sports Medicine (1995)

OBJECTIVE: To test the hypothesis that stress reducing techniques such as meditation alter immune responses after strenous physical stress. METHODS: The hypothesis was tested by studying six meditating and six non-meditating male runners in a concurrent, controlled design. After a period of six months with meditation for the experimental group, blood samples were taken immediately before and after a maximum oxygen uptake test (VO2max). RESULTS: The increase in CD8+ T cells after VO2max was significantly less in the meditation group than in the control group (P = 0.04). The amount of CD2+ cells doubled after VO2max, mainly because of a rise in the CD8+ fraction. CONCLUSIONS: Meditation may modify the suppressive influence of strenous physical stress on the immune system.
Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity of recirculating lymphocytes for high-endothelial venules.
Authors: H B Stamper, J J Woodruff
Journal: The Journal of Experimental Medicine (1976)

An in vitro model is described for studying the interaction between lymphocytes and high-endothelial venules (HEV) of lymph nodes. Rat or mouse lymphocytes which were layered over fixed sections of syngeneic lymph nodes adhered selectively to the endothelium of HEV but did not bind to other vascular endothelia. Evidence is presented that adherence to HEV in vitro is a property of recirculating lymphocytes and not a characteristic of cells which are unable to home into lymph nodes in vivo.
Rhythm Control versus Rate Control for Atrial Fibrillation and Heart Failure
Authors: Denis Roy, Mario Talajic, Stanley Nattel, D. George Wyse, Paul Dorian, Kerry L. Lee, Martial G. Bourassa, J. Malcolm O. Arnold, Alfred E. Buxton, A. John Camm, Stuart J. Connolly, Marc Dubuc, Anique Ducharme, Peter G. Guerra, Stefan H. Hohnloser, Jean Lambert, Jean-Yves Le Heuzey, Gilles O'Hara, Ole Dyg Pedersen, Jean-Lucien Rouleau, Bramah N. Singh, Lynne Warner Stevenson, William G. Stevenson, Bernard Thibault, Albert L. Waldo
Journal: New England Journal of Medicine (2008)

It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure. This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome. However, the benefits and risks of this approach have not been adequately studied.We conducted a multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with a left ventricular ejection fraction of 35% or less, symptoms of congestive heart failure, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes.A total of 1376 patients were enrolled (682 in the rhythm-control group and 694 in the rate-control group) and were followed for a mean of 37 months. Of these patients, 182 (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 (25%) in the rate-control group (hazard ratio in the rhythm-control group, 1.06; 95% confidence interval, 0.86 to 1.30; P=0.59 by the log-rank test). Secondary outcomes were similar in the two groups, including death from any cause (32% in the rhythm-control group and 33% in the rate-control group), stroke (3% and 4%, respectively), worsening heart failure (28% and 31%), and the composite of death from cardiovascular causes, stroke, or worsening heart failure (43% and 46%). There were also no significant differences favoring either strategy in any predefined subgroup.In patients with atrial fibrillation and congestive heart failure, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy. (ClinicalTrials.gov number, NCT00597077.)
Hepatic nitric oxide production following acute endotoxemia in rats is mediated by increased inducible nitric oxide synthase gene expression
Authors: Debra L. Laskin, Marina Rodriguez Del Valle, Diane E. Heck, Shaw-Min Hwang, S. Tsuyoshi Ohnishi, Stephen K. Durham, Nancy L. Goller, Jeffrey D. Laskin
Journal: Hepatology (1995)

In the present studies, we analyzed the effects of acute endotoxemia on hepatocyte nitric oxide production and functional activity. Treatment of rats with 5 mg/kg of lipopolysaccharide (LPS), which induces acute endotoxemia, caused an increase in nitric oxide production in the liver, as measured by electron paramagnetic spin trapping, which was evident within 6 hours. This was associated with expression of inducible nitric oxide synthase (iNOS) messenger (m) RNA in hepatocytes and in sinusoidal cells throughout the liver lobule. Acute endotoxemia also caused alterations in hepatic structure, including hypertrophy, vacuolization, and chromosomal emargination, however these changes were not apparent for 24 to 48 hours. Hepatocytes isolated from endotoxemic rats released increased amounts of nitric oxide, measured by nitrite production, in response to interferon gamma (gamma-IFN) alone or in combination with LPS, tumor necrosis factor alpha, macrophage-colony stimulating factor, granulocyte/macrophage-colony stimulating factor, or hepatocyte growth factor. These results show that hepatocytes are sensitized by acute endotoxemia to respond to inflammatory mediators and growth factors. Increased nitrite production by hepatocytes was due to increased expression of iNOS mRNA and protein and was correlated with the time following induction of acute endotoxemia. Thus, cells isolated 48 hours after induction of acute endotoxemia released significantly more nitrite than cells recovered after 6 hours, a response that was not due to alterations in hepatocyte viability. Hepatocytes isolated from endotoxemic rats also exhibited a marked increase in proliferative capacity when compared with cells from control rats. Nitric oxide production by hepatocytes in vitro was associated with inhibition of cell growth and protein synthesis, which was reversed by the nitric oxide synthase inhibitor, NG-monomethyl-l-arginine (L-NMMA). Agarose gel electrophoresis showed extensive cytoplasmic DNA fragmentation in hepatocytes treated with LPS and gamma-IFN, a characteristic of apoptosis, which was also reversed by L-NMMA. These results, together with our findings that treatment of rats with an inhibitor of nitric oxide synthase partially reversed the structural alterations in the liver associated with acute endotoxemia suggest that nitric oxide may contribute to the pathophysiologic response to this bacterially derived toxin.
Third-hand tobacco smoke exposure and respiratory complaints in children: A cross-sectional study
Authors: Sasha Hutchinson, John Penders, Jean Muris, Constant van Schayck, Edward Dompeling, Ilse Mesters
Journal: European Respiratory Journal (2013)

Background   Much is known about the respiratory health effects of second-hand smoke (SHS) exposure in children, but not of third-hand smoke (THS) exposure. We evaluated the relationship between SHS and THS exposure and respiratory complaints in children aged 0-13 years living in South-Limburg, the Netherlands.    Methods   A sample of 10.000 families with a child aged 0-13 years were asked to complete a questionnaire (91 items) for their youngest child, including questions about the age and gender of the child, family characteristics, respiratory health of the child and parental smoking behaviour. Data were analysed with multiple logistic regression.    Results   19% (n=1899) responded. Current SHS exposure in children was reported in 20.5% of the children. 5% of the children without current SHS exposure were exposed to THS. Furthermore, SHS exposure was not associated with an increased risk for respiratory complaints in children. THS exposure was associated with respiratory tract infections in the past 12 months (OR adjusted : 2.13; 95%CI: 1.04-4.36;  p =0.04) and recent wheezing (OR adjusted : 2.61; 95%CI: 1.19-5.71;  p =0.02) in children.    Conclusions   Unlike previous studies, SHS exposure was not significantly associated with increased risk of respiratory complaints in children, most likely due to the study limitations: cross-sectional design, response rate, selection bias and parental underreporting of their smoking behaviour. Despite these limitations, THS exposure was significantly associated with increased risk for respiratory complaints in children. This adds to the limited knowledge about the health effects of THS exposure in children and suggests that more research on this topic is needed.