tbuckley/cabot-search huggingface dataset:
Effect of immunoglobulin light chains from hemodialysis and continuous ambulatory peritoneal dialysis patients on polymorphonuclear leukocyte functions.
Authors: G Cohen, M Haag-Weber, B Mai, R Deicher, W H Hörl
Journal: Journal of the American Society of Nephrology (1995)

Circulating plasma factors accumulating in the serum of uremic patients have the potential to inhibit essential functions of polymorphonuclear leukocytes (PMNL). As a consequence, these factors can contribute to the increased risk for bacterial infections generally found in uremic patients. Free immunoglobulin light chains that are present in the serum of healthy adults at low levels appear in the serum of uremic patients at significantly higher levels. Therefore, kappa and lambda light chains in their monomeric and dimeric forms were isolated from hemodialysis and continuous ambulatory peritoneal dialysis patients and their potential to inhibit essential PMNL functions in in vitro assays was tested. It was found that all isolates tested were able to inhibit deoxyglucose uptake, a measure for the state of activation of PMNL, as well as chemotaxis. In contrast, free immunoglobulin light chains had no influence on the phagocytotic functions of PMNL. It was concluded that free immunoglobulin light chains are able to act as uremic toxins by interfering with essential PMNL functions and that their serum levels and fate during the treatment of uremic patients should be taken into consideration.
High-Dose Therapy and Autologous Stem-Cell Transplantation in Angioimmunoblastic Lymphoma: Complete Remission at Transplantation Is the Major Determinant of Outcome—Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Charalampia Kyriakou, Carmen Canals, Anthony Goldstone, Dolores Caballero, Bernd Metzner, Guido Kobbe, Hans-Jochem Kolb, Joachim Kienast, Peter Reimer, Jurgen Finke, Gunnar Oberg, Ann Hunter, Niklas Theorin, Anna Sureda, Norbert Schmitz
Journal: Journal of Clinical Oncology (2007)

Patients with angioimmunoblastic T-cell lymphoma (AITL) have poor prognoses with current conventional chemotherapy. The aim of this study was to evaluate the effect of high-dose therapy (HDT) followed by autologous stem-cell transplantation (ASCT) on patients with AITL.We report a retrospective, multicenter study of 146 patients with AITL who received ASCT. The source of the stem cells was peripheral blood in 143 patients. The conditioning regimen varied, and 74% of the patients received carmustine and 1,3-bis(2-chloroethyl)-1-nitrosourea; etoposide; ara-C; and melphalan chemotherapy.After a median follow-up of 31 months (range, 3 to 174 months), 95 patients (65%) remained alive, and 51 patients (35%) died. Forty-two patients died as a result of disease progression, and nine died as a result of regimen-related toxicity. The cumulative incidence of nonrelapse mortality was 5% and 7% at 12 and 24 months, respectively. The actuarial overall survival (OS) was 67% at 24 months and 59% at 48 months. The cumulative incidence of relapse was estimated at 40% and 51% at 24 and 48 months, respectively. Disease status at transplantation was the major factor that impacted outcome. Patients who received a transplant during first complete remission (CR) had significantly superior progression-free survival and OS. The estimated PFS rates for patients who received their transplants in CR were 70% and 56% at 24 and 48 months, respectively; 42% and 30% for patients with chemotherapy-sensitive disease at those time points, respectively; and 23% at both time points for patients with chemotherapy-refractory disease.This study shows that HDT and ASCT offers the possibility of long-term disease-free survival to patients with AITL. Early transplantation is necessary to achieve optimal results.
Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout mice
Authors: C. J. Wruck, A. Fragoulis, A. Gurzynski, L.-O. Brandenburg, Y. W. Kan, K. Chan, J. Hassenpflug, S. Freitag-Wolf, D. Varoga, S. Lippross, T. Pufe
Journal: Annals of the Rheumatic Diseases (2010)

<h3>OBJECTIVE</h3> To evaluate the use of cardiac troponin I (cTnI), creatine kinase-MB<sub>mass</sub> (CK-MB<sub>mass</sub>), myosin light chain 1 (MLC 1), and myoglobin in identifying "high risk" patients with chest pain who will experience serious cardiac events (SCEs) in hospital. <h3>DESIGN</h3> Prospective study. <h3>SETTING</h3> University affiliated medical centre in Philadelphia, USA. <h3>PATIENTS</h3> 208 patients with chest pain, at &gt; 7% risk of acute myocardial infarction (MI), but without new ST segment elevation on their presenting ECG. <h3>INTERVENTIONS</h3> cTnI, CK-MB<sub>mass</sub>, MLC 1, and myoglobin concentrations were obtained on admission (0 hour) and at 4, 8, 16, and 24 hours. <h3>MAIN OUTCOME MEASURES</h3> The sensitivity, specificity, positive and negative predictive value, and pre- and post-test probabilities of patients suffering an SCE in hospital were determined. SCEs included cardiac death, acute MI, cardiac arrest, life threatening cardiac arrhythmia, cardiogenic shock, and urgent coronary revascularisation. <h3>RESULTS</h3> Admission concentrations of all markers were poor predictors of SCEs in hospital but improved substantially at subsequent timepoints. cTnI and CK-MB<sub>mass</sub> were consistently the most useful prognostic indicators. If both were negative at 0, 4, and 8 hours, then 99% (95% confidence interval 96% to 100%) of patients remained free from SCEs. The only SCEs not thus predicted were revascularisation procedures and associated complications. Additional tests after 8 hours, or the inclusion of additional markers, did not improve predictive accuracy further. <h3>CONCLUSIONS</h3> Patients with high risk clinical features on admission who have negative cTnI and CK-MB<sub>mass</sub> concentrations at 0, 4, and 8 hours later have a favourable in-hospital prognosis and could be considered for early triage out of coronary care units.
A New Group of Tyrosine Recombinase-Encoding Retrotransposons
Authors: Timothy J. D. Goodwin, Russell T. M. Poulter
Journal: Molecular Biology and Evolution (2004)

A wide variety of novel tyrosine recombinase (YR)-encoding retrotransposons were identified using data emerging from the various eukaryotic genome sequencing projects. Although many of these elements are clearly members of the previously described DIRS group of YR retrotransposons, a substantial number, including elements from a variety of fungi and animals, belong to a distinct and previously unrecognized group. We refer to these latter elements as the Ngaro group after a representative from zebrafish. Like the members of the DIRS group, Ngaro elements encode proteins bearing reverse transcriptase (RT) and ribonuclease H (RH) domains similar to those of long terminal repeat (LTR) retrotransposons. Phylogenetic analyses based on alignments of RT/RH and YR domains, however, indicate that Ngaro and DIRS are anciently diverged groups. Differences in coding capacity also support the distinction between the two groups. For instance, we found that DIRS elements all encode a protein domain which is similar in sequence to the DNA methyltransferases of certain bacteriophages, whereas this domain is absent from all Ngaro elements. Together, the Ngaro and DIRS groups of YR retrotransposons contain elements with an astonishing diversity in structures, with variations in the nature of the associated repeat sequences and in the arrangement and complement of coding regions. In addition they contain elements with some surprising features, such as spliceosomal introns and long overlapping open reading frames.
Airways changes related to air pollution exposure in wheezing children
Authors: P.C. Martins, J. Valente, A.L. Papoila, I. Caires, J. Araújo-Martins, P. Mata, M. Lopes, S. Torres, J. Rosado-Pinto, C. Borrego, I. Annesi-Maesano, N. Neuparth
Journal: European Respiratory Journal (2011)

In this study, we aimed to evaluate the relationship between individual total exposure to air pollution and airway changes in a group of 51 wheezing children. Respiratory status was assessed four times (January 2006, June 2006, January 2007 and June 2007) during a 1-week period through a standardised questionnaire, spirometry, exhaled nitric oxide fraction and pH in exhaled breath condensate (EBC). Concentrations of particles with a 50% cut-off aerodynamic diameter of 10 µm (PM 10 ), O 3 , NO 2 and volatile organic compounds were estimated through direct measurements with an ad hoc device or air pollution modelling in the children's schools and at their homes in the same 4 weeks of the study. For each child, total exposure to the different air pollutants was estimated as a function of pollutant concentrations and daily activity patterns. Increasing total exposure to PM 10 , NO 2 , benzene, toluene and ethylbenzene was significantly associated with a decrease of forced expiratory volume in 1 s (FEV 1 ) and with an increase of change in FEV 1 . Increasing exposure to NO 2 and benzene was also related to a significant decrease of FEV 1 /forced vital capacity. Increasing exposure to PM 10 , NO 2 , benzene and ethylbenzene was associated with acidity of EBC. This study suggests an association in wheezing children between airway changes and total exposure to air pollutants, as estimated by taking into account the concentration in the various microenvironments attended by the children.
Kallikrein 5 induces atopic dermatitis–like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome
Authors: Anaïs Briot, Céline Deraison, Matthieu Lacroix, Chrystelle Bonnart, Aurélie Robin, Céline Besson, Pierre Dubus, Alain Hovnanian
Journal: The Journal of Experimental Medicine (2009)

Netherton syndrome (NS) is a severe genetic skin disease with constant atopic manifestations that is caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, which encodes the protease inhibitor lymphoepithelial Kazal-type–related inhibitor (LEKTI). Lack of LEKTI causes stratum corneum detachment secondary to epidermal proteases hyperactivity. This skin barrier defect favors allergen absorption and is generally regarded as the underlying cause for atopy in NS. We show for the first time that the pro-Th2 cytokine thymic stromal lymphopoietin (TSLP), the thymus and activation-regulated chemokine, and the macrophage-derived chemokine are overexpressed in LEKTI-deficient epidermis. This is part of an original biological cascade in which unregulated kallikrein (KLK) 5 directly activates proteinase-activated receptor 2 and induces nuclear factor κB–mediated overexpression of TSLP, intercellular adhesion molecule 1, tumor necrosis factor α, and IL8. This proinflammatory and proallergic pathway is independent of the primary epithelial failure and is activated under basal conditions in NS keratinocytes. This cell-autonomous process is already established in the epidermis of Spink5−/− embryos, and the resulting proinflammatory microenvironment leads to eosinophilic and mast cell infiltration in a skin graft model in nude mice. Collectively, these data establish that uncontrolled KLK5 activity in NS epidermis can trigger atopic dermatitis (AD)–like lesions, independently of the environment and the adaptive immune system. They illustrate the crucial role of protease signaling in skin inflammation and point to new therapeutic targets for NS as well as candidate genes for AD and atopy.
A randomized phase II study comparing capecitabine alone with capecitabine and oral cyclophosphamide in patients with advanced breast cancer-cyclox II
Authors: V.J. Harvey, K.J. Sharples, R.J. Isaacs, M.B. Jameson, G.M. Jeffery, B.R. McLaren, S. Pollard, G.A. Riley, A.B. Simpson, V.A. Hinder, J.N. Scott, M.V. Dzhelali, M.P. Findlay
Journal: Annals of Oncology (2013)
Presence of a distinct extracellular matrix-degrading metalloproteinase activity in renal tubules.
Authors: P D Walker, G P Kaushal, S V Shah
Journal: Journal of the American Society of Nephrology (1994)

Renal tubular homogenates incubated with [3H]laminin (2 micrograms, 10(5) cpm) at 37 degrees C resulted in time- and protein-dependent laminin degradation (e.g., at 24 h, control = 6,533 +/- 771; experimental = 27,610 +/- 1,023 cpm +/- SE; N = 20). Gel chromatography confirmed that laminin (800 to 900 kd) was degraded to 20- to 50-kd fragments. Laminin degradation was not significantly decreased by serine or cysteine protease inhibitors. In contrast, metal chelators produced marked inhibition (EDTA, 93 +/- 3%; 1,10-phenanthroline, 99 +/- 1%) indicating that, at neutral pH, metalloproteinases were responsible for the laminin degradation. Laminin-degrading activity in renal tubules was not inhibited by the tissue inhibitor of metalloproteinase and was present in an active form. This activity was also present in high concentrations in the renal cortex and medulla but was only minimal in the liver. Further studies of the renal cortex revealed a similar metalloproteinase activity against type IV collagen (11,075 +/- 305; N = 6) and gelatin (41,026 +/- 1,373; N = 6), and this activity was membrane associated (97 +/- 1%; N = 4). Taken together, the characteristics of this renal metalloproteinase indicate that it is distinct from classic matrix-degrading metalloproteinases. The release of this distinct metalloproteinase from damaged renal tubular epithelial cells during injury may result in the production of fragments of laminin or other extracellular matrix components with biologic effects relevant to renal regeneration.
Femorotibial and patellar cartilage loss in patients prior to total knee arthroplasty, heterogeneity, and correlation with alignment of the knee
Authors: R. Von Eisenhart-Rothe, H. Graichen, M. Hudelmaier, T. Vogl, Leena Sharma, Felix Eckstein
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To analyse tibial, femoral, and patellar cartilage loss in patients prior to total knee arthroplasty (TKA), and its correlation with alignment of the knee. <b>Methods:</b> 26 patients (aged 58 to 86 years) with a clinical indication for TKA were investigated. Quantitative end points of cartilage morphology (T scores for cartilage volume normalised to total subchondral bone area) were determined from coronal and axial magnetic resonance image data, using proprietary software. The static alignment of the knee was determined from standing full limb radiographs. <b>Results:</b> The magnitude of cartilage loss (T score of normalised cartilage volume) was highly variable within the knee, correlation coefficients ranging from <i>r</i> = 0.17 to 0.51 between cartilage plates. The correlation of cartilage loss with static alignment of the knee (as a continuous variable) was <i>r</i> = −0.52 (p&lt;0.05) for the medial tibia, −0.38 (not significant) for the medial femur, +0.76 (p&lt;0.001) for the lateral tibia, +0.31 (not significant) for the lateral femur, and −0.09 for the patella. When analysing alignment independent of direction (valgus or varus), the correlation for the patella increased to <i>r</i> = 0.30, but remained non-significant. <b>Conclusions:</b> Cartilage loss was highly variable among patients and among cartilage plates before knee arthroplasty. Its correlation with alignment was stronger for the tibia than for the femur. There was some evidence for an association of alignment and patellar cartilage loss. These findings stimulate further research on the mechanism and cause–effect relation of alignment and knee osteoarthritis using quantitative magnetic resonance imaging technology.
Chronic NSAID use and long-term decline of renal function in a prospective rheumatoid arthritis cohort study
Authors: Burkhard Möller, Menno Pruijm, Sabine Adler, Almut Scherer, Peter M Villiger, Axel Finckh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Non-steroidal anti-inflammatory drugs (NSAIDs) may cause kidney damage. This study assessed the impact of prolonged NSAID exposure on renal function in a large rheumatoid arthritis (RA) patient cohort. <h3>Methods</h3> Renal function was prospectively followed between 1996 and 2007 in 4101 RA patients with multilevel mixed models for longitudinal data over a mean period of 3.2 years. Among the 2739 'NSAID users' were 1290 patients treated with cyclooxygenase type 2 selective NSAIDs, while 1362 subjects were 'NSAID naive'. Primary outcome was the estimated glomerular filtration rate according to the Cockroft–Gault formula (eGFR<sub>CG</sub>), and secondary the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formula equations and serum creatinine concentrations. In sensitivity analyses, NSAID dosing effects were compared for patients with NSAID registration in ≤/&gt;50%, ≤/&gt;80% or ≤/&gt;90% of assessments. <h3>Findings</h3> In patients with baseline eGFR<sub>CG</sub> &gt;30 mL/min, eGFR<sub>CG</sub> evolved without significant differences over time between 'NSAID users' (mean change in eGFR<sub>CG</sub> −0.87 mL/min/year, 95% CI −1.15 to −0.59) and 'NSAID naive' (−0.67 mL/min/year, 95% CI −1.26 to −0.09, p=0.63). In a multivariate Cox regression analysis adjusted for significant confounders age, sex, body mass index, arterial hypertension, heart disease and for other insignificant factors, NSAIDs were an independent predictor for accelerated renal function decline only in patients with advanced baseline renal impairment (eGFR<sub>CG</sub> &lt;30 mL/min). Analyses with secondary outcomes and sensitivity analyses confirmed these results. <h3>Conclusions</h3> NSAIDs had no negative impact on renal function estimates but in patients with advanced renal impairment.
Global Coevolution of Human MicroRNAs and Their Target Genes
Authors: Shahar Barbash, Sagiv Shifman, Hermona Soreq
Journal: Molecular Biology and Evolution (2014)

MicroRNAs (miRNAs) have presumably contributed to the emergence of the novel expression patterns, higher brain functions, and skills underlying human evolution. However, it is incompletely understood how new miRNAs have evolved in the human lineage because their initial emergence predictably entailed deleterious consequences due to their powerful multitarget effects. Here, we report genetic variation and conservation parameters for miRNAs and their predicted targets in the genomes of 1,092 humans and 58 additional organisms. We show that miRNAs were evolutionarily more conserved than their predicted binding sites, which were inversely subject to the accumulation of single-nucleotide variations over short evolutionary timescales. Moreover, the predictably "younger" human-specific miRNAs presented lower genetic variation than other miRNAs; their targets displayed higher genetic variation compared with other miRNA targets in diverse human populations; and neuronal miRNAs showed yet lower levels of genetic variation and were found to target more protein-coding genes than nonneuronal miRNAs. Furthermore, enrichment analysis indicated that targets of human-specific miRNAs primarily perform neuronal functions. Specifically, the genomic regions harboring the vertebrate-conserved neuronal miRNA-132 presented considerably higher conservation scores than those of its target genes throughout evolution, whereas both the recently evolved human miRNA-941 and its acquired targets showed relatively low conservation. Our findings demonstrate inversely correlated genetic variation around miRNAs and their targets, consistent with theories of coevolution of these elements and the predicted role attributed to miRNAs in recent human evolution.
The Causes of Unavoidable Haemorrhage during Miscarriage or Labour when the Placenta is Praevia
Authors: J. M. Duncan
Journal: BMJ (1873)

The needles previously employed by most operators seem to have been larger than it is at all necessary to use, whilst some of them, such as Weiss's modification of Dr. Duncan's needle, are unquestionably very much too large.Recognising the desirability of reducing to a minimum
STRATEGIES FOR ATTENUATING PROTEIN-CATABOLIC RESPONSES IN THE CRITICALLY ILL
Authors: Thomas R. Ziegler, M.D, Christopher Gatzen, FRCS, Douglas W. Wilmore, M.D
Journal: Annual Review of Medicine (1994)

▪ Abstract Specialized enteral and parenteral nutrition are now a standard components of care in critically ill patients. This adjunctive therapy corrects and prevents nutrient deficiencies, attenuates the loss of body protein, and improves clinical outcomes in malnourished patients. Several novel strategies designed to improve the metabolic and clinical effects of specialized nutrition are under vigorous clinical investigation. These new approaches include increased emphasis on enteral feeding to maintain intestinal absorptive, immune, and barrier function; administration of conditionally essential amino acids (glutamine, arginine); use of specialized lipid products and antiox idants; and administration of growth factors such as human growth hormone. Randomized, controlled clinical trials will define the clinical and metabolic efficacy and cost-effectiveness of these therapies in specialized nutrition support.
Substituted Purine Analogues Define a Novel Structural Class of Catalytic Topoisomerase II Inhibitors
Authors: Lars H. Jensen, Annemette V. Thougaard, Morten Grauslund, Birgitte Søkilde, Elisabeth V. Carstensen, Henrik K. Dvinge, Dominic A. Scudiero, Peter B. Jensen, Robert H. Shoemaker, Maxwell Sehested
Journal: Cancer Research (2005)

By screening 1,990 compounds from the National Cancer Institute diversity set library against human topoisomerase IIalpha, we identified a novel catalytic topoisomerase II inhibitor NSC35866, a S6-substituted analogue of thioguanine. In addition to inhibiting the DNA strand passage reaction of human topoisomerase IIalpha, NSC35866 also inhibited its ATPase reaction. NSC35866 primarily inhibited DNA-stimulated ATPase activity, whereas DNA-independent ATPase activity was less sensitive to inhibition. We compared the mode of topoisomerase II ATPase inhibition induced by NSC35866 with that of 12 other substituted purine analogues of different chemical classes. The ability of thiopurines with free SH functionalities to inhibit topoisomerase II ATPase activity was completely abolished by DTT, suggesting that these thiopurines inhibit topoisomerase II ATPase activity by covalently modifying free cysteine residues. In contrast, NSC35866 as well as two O6-substituted guanine analogues, O6-benzylguanine and NU2058, could inhibit topoisomerase II ATPase activity in the presence of DTT, indicating that they have a different mechanism of inhibition. NSC35866 did not increase the level of topoisomerase II covalent cleavable complexes with DNA, indicating that it is a catalytic inhibitor and not a poison. NSC35866 was also capable of inducing a salt-stable complex of topoisomerase II on closed circular DNA. In accordance with these biochemical data, NSC35866 could antagonize etoposide-induced cytotoxicity and DNA breaks in human and murine cancer cells, confirming that NSC35866 also functions as a catalytic topoisomerase II inhibitor in cells.