tbuckley/cabot-search huggingface dataset:
Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE).
Authors: V Kumar, K Stellrecht, E Sercarz
Journal: The Journal of Experimental Medicine (1996)

T cell receptor (TCR)-recognizing regulatory cells, induced after vaccination with self-reactive T cells or TCR peptides, have been shown to prevent autoimmunity. We have asked whether this regulation is involved in the maintenance of peripheral tolerance to myelin basic protein (MBP) in an autoimmune disease model, experimental autoimmune encephalomyelitis (EAE). Antigen-induced EAE in (SJL x B10.PL)F1 mice is transient in that most animals recover permanently from the disease. Most of the initial encephalitogenic T cells recognize MBP Ac1-9 and predominantly use the TCR V beta 8.2 gene segment. In mice recovering from MBP-induced EAE, regulatory CD4+ T cells (Treg) specific for a single immunodominant TCR peptide B5 (76-101) from framework region 3 of the V beta 8.2 chain, become primed. We have earlier shown that cloned B5-reactive Treg can specifically downregulate responses to Ac1-9 and also protect mice from EAE. These CD4 Treg clones predominantly use the TCR V beta 14 or V beta 3 gene segments. Here we have directly tested whether deletion/blocking of the Treg from the peripheral repertoire affects the spontaneous recovery from EAE. Treatment of F1 mice with appropriate V beta-specific monoclonal antibodies resulted in an increase in the severity and duration of the disease; even relapses were seen in one-third to one-half of the Treg-deleted mice. Interestingly, chronic disease in treated mice appears to be due to the presence of Ac1-9-specific T cells. Thus, once self-tolerance to MBP is broken by immunization with the antigen in strong adjuvant, TCR peptide-specific CD4 Treg cells participate in reestablishing peripheral tolerance. Thus, a failure to generate Treg may be implicated in chronic autoimmune conditions.
Biomechanics of Pressure Ulcer in Body Tissues Interacting with External Forces during Locomotion
Authors: Arthur F.T. Mak, Ming Zhang, Eric W.C. Tam
Journal: Annual Review of Biomedical Engineering (2010)

Forces acting on the body via various external surfaces during locomotion are needed to support the body under gravity, control posture, and overcome inertia. Examples include the forces acting on the body via the seating surfaces during wheelchair propulsion, the forces acting on the plantar foot tissues via the insole during gait, and the forces acting on the residual-limb tissues via the prosthetic socket during various movement activities. Excessive exposure to unwarranted stresses at the body-support interfaces could lead to tissue breakdowns commonly known as pressure ulcers, often presented as deep-tissue injuries around bony prominences or as surface damage on the skin. In this article, we review the literature that describes how the involved tissues respond to epidermal loading, taking into account both experimental and computational findings from in vivo and in vitro studies. In particular, we discuss related literature about internal tissue deformation and stresses, microcirculatory responses, and histological, cellular, and molecular observations.
Impact of Stromal Sensitivity on Radiation Response of Tumors Implanted in SCID Hosts Revisited
Authors: Mónica García-Barros, Tin Htwe Thin, Jerzy Maj, Carlos Cordon-Cardo, Adriana Haimovitz-Friedman, Zvi Fuks, Richard Kolesnick
Journal: Cancer Research (2010)

Severe combined immunodeficient (SCID) mice carry a germ-line mutation in DNA-PK, associated with deficiency in recognition and repair DNA double-strand breaks. Thus, SCID cells and tissues display increased sensitivity to radiation-induced postmitotic (clonogenic) cell death. Nonetheless, the single-radiation doses required for 50% permanent local control (TCD(50)) of tumors implanted in SCID mice are not significantly different from the TCD(50) values of the same tumors in wild-type hosts. Whereas the tumor stroma is derived from the host, the observation that tumors implanted in SCID mice do not exhibit hypersensitivity to radiation might imply that stromal endothelial elements do not contribute substantially to tumor cure by ionizing radiation. Here, we challenge this notion, testing the hypothesis that ASMase-mediated endothelial apoptosis, which results from plasma membrane alterations, not DNA damage, is a crucial element in the cure of tumors in SCID mice by single-dose radiotherapy (SDRT). We show that the endothelium in MCA/129 fibrosarcomas and B16 melanomas exhibits a wild-type apoptotic phenotype in SCID hosts, abrogated in tumors in SCID(asmase-/-) littermates, which also acquire resistance to SDRT. Conversion into a radioresistant tumor phenotype when implanted in SCID(asmase-/-) hosts provides compelling evidence that cell membrane ASMase-mediated microvascular dysfunction, rather than DNA damage-mediated endothelial clonogenic lethality, plays a mandatory role in the complex pathophysiologic mechanism of tumor cure by SDRT, and provides an explanation for the wild-type SDRT responses reported in tumors implanted in SCID mice.
Problems in the Therapeutic Community
Authors: DAVID E. RASKIN
Journal: American Journal of Psychiatry (1971)

The author discusses the following problems encountered in attempting to establish a milieu treatment program for acute psychiatric patients: tyring to set up a ward culture in the midst of frequent admissions and discharges; the patients' inability to handle the principles of democracy and permissiveness; the spreading of problems encountered by one patient group to another patient group; and the blurring of staff roles.
Oncostatin M promotes biphasic tissue factor expression in smooth muscle cells: evidence for Erk-1/2 activation
Authors: Toshiya Nishibe, Graham Parry, Atsushi Ishida, Salim Aziz, Jacqueline Murray, Yatin Patel, Salman Rahman, Kurt Strand, Keiko Saito, Yuji Saito, William P. Hammond, Geoffrey F. Savidge, Nigel Mackman, Errol S. Wijelath
Journal: Blood (2001)

Abstract Tissue factor (TF), a transmembrane glycoprotein, initiates the extrinsic coagulation cascade. TF is known to play a major role in mediating thrombosis and thrombotic episodes associated with the progression of atherosclerosis. Macrophages at inflammatory sites, such as atherosclerotic lesions, release numerous cytokines that are capable of modulating TF expression. This study examined the role of oncostatin M (OSM), a macrophage/ T-lymphocyte–restricted cytokine, in the expression of TF in vascular smooth muscle cells (SMCs). It is reported here that OSM stimulated a biphasic and sustained pattern of TF messenger RNA (mRNA). The effect of OSM on TF mRNA expression was regulated at the transcriptional level as determined by nuclear run-offs and transient transfection of a TF promoter-reporter gene construct. OSM-induced TF expression was regulated primarily by the transcription factor NF-κB. Activation of NF-κB by OSM did not require IκB-α degradation. Inhibition of MEK activity by U0126 prevented OSM-induced TF expression by suppressing NF-κB DNA binding activity as determined by gel-shift analysis. Further, inhibition of Erk-1/2 protein by antisense treatment resulted in suppression of TF mRNA expression, indicating a role for Erk-1/2 in modulating NF-κB DNA binding activity. These studies suggest that the induced expression of TF by OSM is primarily through the activation of NF-κB and that activation of NF-κB is regulated in part by the MEK/Erk-1/2 signal transduction pathway. This study indicates that OSM may play a key role in promoting TF expression in SMCs within atherosclerotic lesions.
COL4A3/COL4A4 Mutations Producing Focal Segmental Glomerulosclerosis and Renal Failure in Thin Basement Membrane Nephropathy
Authors: Konstantinos Voskarides, Loukas Damianou, Vassos Neocleous, Ioanna Zouvani, Stalo Christodoulidou, Valsamakis Hadjiconstantinou, Kyriacos Ioannou, Yiannis Athanasiou, Charalampos Patsias, Efstathios Alexopoulos, Alkis Pierides, Kyriacos Kyriacou, Constantinos Deltas
Journal: Journal of the American Society of Nephrology (2007)

Mutations in the COL4A3/COL4A4 genes of type IV collagen have been found in approximately 40% of cases of thin basement membrane nephropathy, which is characterized by microscopic hematuria and is classically thought to cause proteinuria and chronic renal failure rarely. Here we report our observations of 116 subjects from 13 Cypriot families clinically affected with thin basement membrane nephropathy. These families first came to our attention because they segregated microscopic hematuria, mild proteinuria, and variable degrees of renal impairment, but a dual diagnosis of focal segmental glomerulosclerosis (FSGS) and thin basement membrane nephropathy was made in 20 biopsied cases. Molecular studies identified founder mutations in both COL4A3 and COL4A4 genes in 10 families. None of 82 heterozygous patients had any extrarenal manifestations, supporting the diagnosis of thin basement membrane nephropathy. During follow-up of up to three decades, 31 of these 82 patients (37.8%) developed chronic renal failure and 16 (19.5%) reached end-stage renal disease. Mutations G1334E and G871C were detected in seven and three families, respectively, and were probably introduced by founders. We conclude that these particular COL4A3/COL4A4 mutations either predispose some patients to FSGS and chronic renal failure, or that thin basement membrane nephropathy sometimes coexists with another genetic modifier that is responsible for FSGS and progressive renal failure. The findings presented here do not justify the labelling of thin basement membrane nephropathy as a benign condition with excellent prognosis.
Low Levels of Insulin-Like Growth Factor Type 1 Receptor Expression at Cancer Cell Membrane Predict Liver Metastasis in Dukes’ C Human Colorectal Cancers
Authors: Michio Nakamura, Shin’ichi Miyamoto, Hiroyuki Maeda, Shi-chuan Zhang, Takafumi Sangai, Genichiro Ishii, Takahiro Hasebe, Yasushi Endoh, Norio Saito, Masahiro Asaka, Atsushi Ochiai
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The aim of this study was to evaluate the prognostic significance of insulin-like growth factor type 1 receptor (IGF-1R) expression in Dukes’ C human colorectal cancers (CRCs). Experimental Design: Immunohistochemical staining for IGF-1R was done on formalin-fixed, paraffin-embedded specimens from 161 patients with curatively resected Dukes’ C CRC and at least 5-year follow-up periods. We investigated the association between the levels of IGF-1R expression and the clinicopathologic parameters. To evaluate the accurate prognostic value of IGF-1R expression, we investigated two patterns of recurrence-free survival (RFS) according to the mode of recurrence, the hepatic-RFS (H-RFS), and the nonhepatic-RFS (nH-RFS). The influence of the pattern of IGF-1R immunostaining (membranous or cytoplasmic) on RFS was also estimated. Results: High (diffuse staining) and low (focal staining) levels of IGF-1R expression were found in 45 (28%) and 116 (72%) specimens, respectively. The recurrence rate was significantly higher in the latter group (49 of 116) than the former group (9 of 45; P = 0.01). H-RFS was significantly longer for the former group than the latter group (P = 0.021), whereas no difference was found in nH-RFS between the two groups (P = 0.121). In multivariate analysis, the level of IGF-1R expression was an independent factor for H-RFS (P = 0.015) as were the depth of invasion and lymph vessel invasion (P = 0.006 and 0.022, respectively). Using a combination of the level of IGF-1R expression and these two factors, the prognostic value was further increased. When IGF-1R staining patterns (membranous or cytoplasmic) were compared, membrane staining of IGF-1R possessed prognostic significance. Conclusions: In Dukes’ C CRC, focal membrane expression of IGF-1R in the primary tumor can predict a high risk of recurrence, especially liver metastasis. Understanding the mechanisms involved could lead to new therapeutic approaches for advanced CRC.
Aortic Distensibility Independently Affects Exercise Tolerance in Patients With Dilated Cardiomyopathy
Authors: Stefano Bonapace, Andrea Rossi, Mariantonietta Cicoira, Lorenzo Franceschini, Giorgio Golia, Luisa Zanolla, Paolo Marino, Piero Zardini
Journal: Circulation (2003)

Peak exercise oxygen consumption (VO2) is crucial for the prognostic stratification of patients with congestive heart failure, but its hemodynamic determinants are still not completely understood. Aortic wall elasticity modulates left ventricular function and coronary blood flow. Whether an increased aortic pulse-wave velocity (PWV), a known marker of arterial stiffness, may predict peak VO2 in patients with dilated cardiomyopathy (DCM) has to be clarified.A total of 78 patients with clinical diagnosis of DCM (aged 62+/-11 years; female 29%; mean ejection fraction 34+/-9%) were selected. All patients underwent a complete echocardiographic-Doppler evaluation. Aortic PWV was measured by Doppler ultrasonography immediately before the exercise. A bicycle exercise test with expiratory gas exchange monitoring was performed to determine VO2 . Plasma concentration of the amino-terminal propeptide of type III procollagen (PIIINP), a marker of extracellular matrix turnover, was determined. Mean PWV was 5.7+/-2.2 m/s, and VO2 was 16.5+/-4.5 mL x kg(-1) x min(-1). The hemodynamic variables correlated with VO2 were PWV (r=-0.39, P=0.0007) and stroke volume (r=0.38, P=0.002). In a multivariate analysis, PWV (P=0.04) and stroke volume (P=0.05) were independently correlated with VO2 , accounting for 34% of its variance. PIIINP levels correlated with PWV (r=0.35, P=0.002) and a more restrictive diastolic filling pattern (r=0.40, P=0.02).Increased aortic stiffness measured by PWV is an independent predictor of peak VO2 and could partially explain exercise intolerance in patients with DCM.
Differential expression analysis for sequence count data
Authors: Simon Anders, Wolfgang Huber
Journal: Genome biology (2010)

High-throughput sequencing assays such as RNA-Seq, ChIP-Seq or barcode counting provide quantitative readouts in the form of count data. To infer differential signal in such data correctly and with good statistical power, estimation of data variability throughout the dynamic range and a suitable error model are required. We propose a method based on the negative binomial distribution, with variance and mean linked by local regression and present an implementation, DESeq, as an R/Bioconductor package.
The CONSORT Statement: Revised Recommendations for Improving the Quality of Reports of Parallel-Group Randomized Trials
Authors: David Moher
Journal: JAMA (2001)

To comprehend the results of a randomized controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this article incorporates new evidence and addresses some criticisms of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Comment. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from 4 stages of a trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, according to each intervention group, included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.
Which brain mechanism cannot count beyond four?
Authors: Pieter R. Roelfsema, Victor A. F. Lamme
Journal: Behavioral and Brain Sciences (2001)

Cowan makes an intriguing case for a fundamental limit in the number of chunks that can be stored in short term memory (STM). Chunks are collections of concepts that have strong associations to one another and much weaker associations to other chunks. A translation of this definition for the visual domain would be that a visual chunk is a collection of features that belong to the same perceptual group (see also Mahoney &amp; Ullman 1988). Here, we will first address the neuronal mechanisms that may demarcate visual chunks. Then we critically evaluate to what extent these mechanisms might be responsible for the limit on the number of chunks that can be held in STM. We conclude that the clarity with which the psychophysical data point to the number four is not matched by a similarly clear limit imposed by physiological mechanisms.
Treatment Trends for Prostate Cancer—Reply
Authors: Matthew R. Cooperberg, Peter R. Carroll
Journal: JAMA (2015)

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Off-Pump vs Conventional Coronary Artery Bypass Grafting: Early and 1-Year Graft Patency, Cost, and Quality-of-Life Outcomes
Authors: John D. Puskas, Willis H. Williams, Elizabeth M. Mahoney, Philip R. Huber, Peter C. Block, Peggy G. Duke, James R. Staples, Katherine E. Glas, J. Jeffrey Marshall, Mark E. Leimbach, Susan A. McCall, Rebecca J. Petersen, Dianne E. Bailey, William S. Weintraub, Robert A. Guyton
Journal: JAMA (2004)

attributable to cardiopulmonary bypass, 1-3 US surgeons performed approximately 21% of coronary artery bypass operations off-pump in 2002. 46][7][8][9] Two prospective, randomized studies 10,11 and all but a few 12 retrospective comparisons have reported significantly fewer grafts in OPCAB.Retrospective studies among selected patients showing sig-
Response Letters Regarding Article, “Masking Inferior Infarction by Anterior Myocardial Injury”
Authors: Bodh Das, Changchun Deng
Journal: Circulation (2007)

We thank the authors of the 4 letters to the editor for their interest in our work. 1All of the letters raise the interesting and important issue of lead misplacement, which is indeed suggested when one compares the morphology of the P waves in the limb leads in Figure 2 against Figure 1 and Figure 3 in our article.However, the authors of the letters might not have considered other elements on the ECG tracings that do not support such an interpretation.In extensive anterior myocardial injury, there is concordant ST elevation in lead I and aVL; only in high lateral MI might the ST elevation be limited to lead I and aVL.The concordance is clearly seen in lead I and aVL in Figure 2. If, on the other hand, the left-arm and left-leg leads are interchanged, as suspected, then the aVF in Figure 2 would be really aVL and should, therefore, show significant ST elevation concordant to anterior myocardial injury; and lead II, which would be lead "I," should also show significant ST elevation.Furthermore, leads II, III, and aVF (baseline, Figure 1 and 3) have some slight but persistent ST elevation.On development of an anterior myocardial injury (Figure 2), ST in aVF became flat and somewhat depressed, whereas ST in lead II was still slightly elevated, although markedly decreased compared with ST elevation in lead II of Figure 3.This suggests reciprocal changes in inferior leads as well.Devoid of characteristic P-wave changes, repolarization concordance suggests no lead misplacement.Whether repolarization concordance should prevail over P-wave changes in determining lead misplacement would depend on how absolute the value of P waves is in diagnosing lead misplacement.A very elegant work by Ho and Ho 2 has drawn up an algorithm to detect lead misplacement on the basis of the invariability of counterclockwise loops of normal P waves, with clockwise P loops being a hallmark of lead misplacement.However, Ho and Ho 2 clearly specify the limitations of the algorithm in the presence of interatrial conduction delay and left atrial enlargement.A maximum P duration of 140 ms is seen in aVR, and there is a "chad"-like notching of P waves in leads I 1. Deng C, Das B. Masking inferior infarction by anterior myocardial injury.
Reproducibility of exhaled breath condensate pH in chronic obstructive pulmonary disease
Authors: Z. Borrill, C. Starkey, J. Vestbo, D. Singh
Journal: European Respiratory Journal (2005)

Increasingly, exhaled breath condensate (EBC) is being used to sample airway fluid from the lower respiratory tract. EBC pH may be a biomarker of airway inflammation in chronic obstructive pulmonary disease (COPD). In this study, the reproducibility of EBC pH in COPD was investigated. A total of 36 COPD patients and 12 healthy nonsmoking subjects participated in several investigations: duration of argon deaeration, within-sample variability, effect of freezing, leaving samples at room temperature, nose-peg use, within- (WD) and between-day (BD) variability. Analysis of repeated measurements was performed using the Bland–Altman method with limits of agreement (LOA; mean difference±2 sd ). Wider LOA indicate greater variability. EBC pH became significantly higher with argon deaeration for ≤5 min. Variability during sample analysis was minimal; LOA of within-sample variability, freezing for 3 months and leaving at room temperature for 3 h were −0.29–0.45, −0.37–0.42 and −0.13–0.09, respectively. In contrast, variability due to nose-peg use (LOA −1.46–1.99), WD (LOA −1.50–2.48) and BD variability (LOA −2.52–3.02) were higher in COPD. In healthy nonsmoking subjects, nose-peg use (LOA −0.27–0.23), WD (LOA −0.33–0.40) and BD variability (LOA −0.46–0.44) were more reproducible. In conclusion, the variability of exhaled breath condensate pH in chronic obstructive pulmonary disease patients is mainly due to changes in airway pH over time, which are not seen in healthy nonsmoking subjects. Reasons for these fluctuations in exhaled breath condensate pH are unclear and require further investigation.