tbuckley/cabot-search huggingface dataset:
Inhaled Nitric Oxide Effects on Lung Structure and Function in Chronically Ventilated Preterm Lambs
Authors: Richard D. Bland, Kurt H. Albertine, David P. Carlton, Amy J. MacRitchie
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Inhaled nitric oxide (iNO) can reverse neonatal pulmonary hypertension and bronchoconstriction and reduce proliferation of cultured arterial and airway smooth muscle cells.To see if continuous iNO from birth might reduce pulmonary vascular and respiratory tract resistance (PVR, RE) and attenuate growth of arterial and airway smooth muscle in preterm lambs with chronic lung disease.Eight premature lambs received mechanical ventilation for 3 weeks, four with and four without iNO (5-15 ppm). Four term lambs, mechanically ventilated without iNO for 3 weeks, served as additional control animals.PVR and RE were measured weekly. After 3 weeks, lung tissue was processed for quantitative image analysis of smooth muscle abundance around small arteries (SMart) and terminal bronchioles (SMtb). Radial alveolar counts were done to assess alveolar number. Endothelial NO synthase (eNOS) protein in arteries and airways was measured by immunoblot analysis.At study's end, PVR was similar in iNO-treated and untreated preterm lambs; PVR was less in iNO-treated preterm lambs compared with term control animals. RE in iNO-treated lambs was less than 40% of RE measured in preterm control animals. SMart was similar in iNO-treated and both groups of control lambs; SMtb in lambs given iNO was significantly less (approximately 50%) than in preterm control animals. Radial alveolar counts of iNO-treated lambs were more than twice that of preterm control animals. eNOS was similar in arteries and airways of iNO-treated preterm lambs compared with control term lambs.iNO preserves structure and function of airway smooth muscle and enhances alveolar development in preterm lambs with chronic lung disease.
Anergy in Peripheral Memory Cd4+ T Cells Induced by Low Avidity Engagement of T Cell Receptor
Authors: Saied Mirshahidi, Ching-Tai Huang, Scheherazade Sadegh-Nasseri
Journal: The Journal of Experimental Medicine (2001)

Induction of tolerance in self-reactive memory T cells is an important process in the prevention of autoimmune responses against peripheral self-antigens in autoimmune diseases. Although naive T cells can readily be tolerized, memory T cells are less susceptible to tolerance induction. Recently, we demonstrated that low avidity engagement of T cell receptor (TCR) by low densities of agonist peptides induced anergy in T cell clones. Since memory T cells are more responsive to lower antigenic stimulation, we hypothesized that a low avidity TCR engagement may induce tolerance in memory T cells. We have explored two antigenic systems in two transgenic mouse models, and have tracked specific T cells that are primed and show memory phenotype. We demonstrate that memory CD4+ T cells can be rendered anergic by presentation of low densities of agonist peptide–major histocompatibility complex complexes in vivo. We rule out other commonly accepted mechanisms for induction of T cell tolerance in vivo, such as deletion, ignorance, or immunosuppression. Anergy is the most likely mechanism because addition of interleukin 2–reversed anergy in specific T cells. Moreover, cytotoxic T lymphocyte antigen (CTLA)-4 plays a critical role in the induction of anergy because we observed that there was increased surface expression of CTLA-4 on anergized T cells, and that injection of anti–CTLA-4 blocking antibody restored anergy in vivo.
A clinical study assessing the tolerability and biological effects of infliximab, a TNF-α inhibitor, in patients with advanced cancer
Authors: E.R. Brown, K.A. Charles, S.A. Hoare, R.L. Rye, D.I. Jodrell, R.E. Aird, R. Vora, U. Prabhakar, M. Nakada, R.E. Corringham, M. DeWitte, C. Sturgeon, D. Propper, F.R. Balkwill, J.F. Smyth
Journal: Annals of Oncology (2008)
New strategies and emerging technologies for massively parallel sequencing: applications in medical research
Authors: Elaine R Mardis
Journal: Genome Medicine (2009)

A variety of techniques that specifically target human gene sequences for differential capture from a genomic sample, coupled with next-generation, massively parallel DNA sequencing instruments, is rapidly supplanting the combination of polymerase chain reaction and capillary sequencing to discover coding variants in medically relevant samples. These studies are most appropriate for the sample numbers necessary to identify both common and rare single nucleotide variants, as well as small insertion or deletion events, which may cause complex inherited diseases. The same massively parallel sequencers are simultaneously being used for whole-genome resequencing and comprehensive, genome-wide variant discovery in studies of somatic diseases such as cancer. Viral and microbial researchers are using next-generation sequences to identify unknown etiologic agents in human diseases, to study the viral and microbial species that occupy surfaces of the human body, and to inform the clinical management of chronic infectious diseases such as human immunodeficiency virus (HIV). Taken together, these approaches are dramatically accelerating the pace of human disease research and are already impacting patient care.
Early and Sustained Survival Benefit Associated With Statin Therapy at the Time of Percutaneous Coronary Intervention
Authors: Albert W. Chan, Deepak L. Bhatt, Derek P. Chew, Martin J. Quinn, David J. Moliterno, Eric J. Topol, Stephen G. Ellis
Journal: Circulation (2002)

Background — Long-term administration of statin therapy has been shown to reduce major coronary events and cardiac mortality within randomized clinical trials. In addition to lowering lipids, statins favorably affect platelet adhesion, thrombosis, endothelial function, inflammation, and plaque stability, which may potentially improve outcome after percutaneous coronary intervention (PCI). Therefore, we hypothesized that statin therapy has an early beneficial effect among patients undergoing PCI. Methods and Results — Each year from 1993 to 1999, we prospectively collected data among the first 1000 patients undergoing PCI. Patients who presented with acute or recent myocardial infarction or cardiogenic shock were excluded from the analysis. Baseline, procedural, and 6-month data of statin-treated and non–statin-treated patients were compared. Propensity score and multivariate survival analysis were used to adjust for heterogeneity between the two groups. Of 5052 patients who completed follow-up, 26.5% were treated with statin at the time of the procedure. Statin therapy was associated with a mortality reduction at 30 days (0.8% versus 1.5%; hazard ratio, 0.53; P =0.048) and at 6 months (2.4% versus 3.6%; hazard ratio, 0.67; P =0.046). After adjusting for the propensity to receive statin therapy before the procedure and other confounders, statin therapy remained an independent predictor for survival at 6 months after coronary intervention (hazard ratio, 0.65; 95% CI, 0.42 to 0.99; P =0.045). Conclusions — In this large study cohort, statin therapy among PCI patients seems to be associated with a significant mortality advantage at early and intermediate-term follow-up.
Serial MR diffusion to predict treatment response in high-grade pediatric brain tumors: a comparison of regional and voxel-based diffusion change metrics
Authors: D. Rodriguez Gutierrez, M. Manita, T. Jaspan, R. A. Dineen, R. G. Grundy, D. P. Auer
Journal: Neuro-Oncology (2013)

Assessment of treatment response by measuring tumor size is known to be a late and potentially confounded response index. Serial diffusion MRI has shown potential for allowing earlier and possibly more reliable response assessment in adult patients, with limited experience in clinical settings and in pediatric brain cancer. We present a retrospective study of clinical MRI data in children with high-grade brain tumors to assess and compare the values of several diffusion change metrics to predict treatment response. Eighteen patients (age range, 1.9–20.6 years) with high-grade brain tumors and serial diffusion MRI (pre- and posttreatment interval range, 1–16 weeks posttreatment) were identified after obtaining parental consent. The following diffusion change metrics were compared with the clinical response status assessed at 6 months: (1) regional change in absolute and normalized apparent diffusivity coefficient (ADC), (2) voxel-based fractional volume of increased (fiADC) and decreased ADC (fdADC), and (3) a new metric based on the slope of the first principal component of functional diffusion maps (fDM). Responders (n = 12) differed significantly from nonresponders (n = 6) in all 3 diffusional change metrics demonstrating higher regional ADC increase, larger fiADC, and steeper slopes (P < .05). The slope method allowed the best response prediction (P < .01, η2 = 0.78) with a classification accuracy of 83% for a slope of 58° using receiver operating characteristic (ROC) analysis. We demonstrate that diffusion change metrics are suitable response predictors for high-grade pediatric tumors, even in the presence of variable clinical diffusion imaging protocols.
P34 Characterising T cell sub-populations in pulmonary hypertension
Authors: A. Shepherd, K. Hopkinson, D. Kiely, C. Elliot, R. Condliffe, D. Crossman, A. Pockley, A. Lawrie
Journal: Thorax (2010)

<h3>Introduction</h3> Pulmonary arterial hypertension (PAH) is characterised by an increase in pulmonary vascular resistance which leads to right ventricular failure and death. Given that PAH is associated with HIV (in which CD4<sup>+</sup> lymphocytes are depleted), and that athymic rats demonstrate heightened pulmonary vascular remodelling in the SUGEN model, suggests that inflammation plays an important role in disease pathogenesis. T cells might therefore dampen rather than accentuate PAH. <h3>Hypothesis9</h3> Reduced CD4<sup>+</sup> T cell numbers and/or an increase in the prevalence, activation and function of naturally-occurring immunoregulatory T (Treg) cells are a “second hit” in the pathogenesis of PAH′. <h3>Methodology</h3> The T cell subset composition (CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup>) and prevalence of Treg cells (CD4<sup>+</sup>CD25<sup>bright</sup>, CD4<sup>+</sup>CD25<sup>bright</sup>CD127<sup>dim</sup>, CD4<sup>+</sup>CD25<sup>bright</sup>CD127<sup>dim</sup>Foxp3<sup>+</sup>, CD4<sup>+</sup>CD25<sup>bright</sup>Foxp3<sup>+</sup>) in the peripheral blood of patients with suspected PAH attending the Pulmonary Vascular Disease Unit and corresponding controls (healthy, no PAH at right heart catheterisation with and without SSc) were determined using multi-parameter flow cytometry. The activation status (CD69 expression) of T cell subsets was also determined. <h3>Findings</h3> Peripheral blood CD3<sup>+</sup> T cells show heightened activation in patients with PAH compared to controls. The proportion of circulating CD4<sup>+</sup> T cells is reduced in patients with Idiopathic PAH (IPAH), and CD4<sup>+</sup>T cells are less activated in patients with limited and diffuse PAH associated with systemic sclerosis (PAH-SSc). The proportion of circulating CD8<sup>+</sup> T cells is higher in patients with diffuse PAH-SSc, and CD8<sup>+</sup> T cells are more activated in patients with IPAH than in their controls. The proportion of CD4<sup>+</sup>CD25<sup>high</sup>FoxP3<sup>+</sup> Treg cells is decreased in patients with limited SSc-PAH compared to controls, and compared with controls, these cells are less activated in IPAH and limited SSc-PAH. <h3>Conclusions</h3> These data indicate that circulating T cell subset profiles are altered in patients with PAH and a changing T cell subpopulation profile might therefore be a potential biomarker of disease or provide insight into future therapeutic targets. Studies to determine the influence of disease progression on T cell subpopulations, the functional properties of Treg cells in patients with PAH and the interaction ofthese cells with pulmonary artery endothelial cells in vitro are currently underway.
Acute Stress Disorder Revisited
Authors: Etzel Cardeña, Eve Carlson
Journal: Annual Review of Clinical Psychology (2011)

Acute stress disorder (ASD) was introduced into the Diagnostic and Statistical Manual (DSM) taxonomy in 1994 to address the lack of a specific diagnosis for acute pathological reactions to trauma and the role that dissociative phenomena play both in the short- and long-term reactions to trauma. In this review, we discuss the history and goals of the diagnosis and compare it with the diagnoses of acute stress reaction, combat stress reaction, and posttraumatic stress disorder (PTSD). We also evaluate the research on the validity and limitations of ASD as a diagnosis, the relationship between peritraumatic dissociation and other symptomatology, the extent to which PTSD is predicted by previous ASD or peritraumatic dissociation, and other important issues such as impairment and risk factors related to ASD. We conclude with our recommendations for changes in DSM-5 criteria and the development of more sophisticated research that considers ASD as but one of two or possibly three common acute posttraumatic syndromes.
Upconversion Nanoparticles for Photodynamic Therapy and Other Cancer Therapeutics
Authors: Chao Wang, Liang Cheng, Zhuang Liu
Journal: Theranostics (2013)

Photodynamic therapy (PDT) is a non-invasive treatment modality for a variety of diseases including cancer.PDT based on upconversion nanoparticles (UCNPs) has received much attention in recent years.Under near-infrared (NIR) light excitation, UCNPs are able to emit high-energy visible light, which can activate surrounding photosensitizer (PS) molecules to produce singlet oxygen and kill cancer cells.Owing to the high tissue penetration ability of NIR light, NIR-excited UCNPs can be used to activate PS molecules in much deeper tissues compared to traditional PDT induced by visible or ultraviolet (UV) light.In addition to the application of UCNPs as an energy donor in PDT, via similar mechanisms, they could also be used for the NIR light-triggered drug release or activation of 'caged' imaging or therapeutic molecules.In this review, we will summarize the latest progresses regarding the applications of UCNPs for photodynamic therapy, NIR triggered drug and gene delivery, as well as several other UCNP-based cancer therapeutic approaches.The future prospects and challenges in this emerging field will be also discussed.
The application of markers (HSP70 GPC3 and GS) in liver biopsies is useful for detection of hepatocellular carcinoma
Authors: Luca Di Tommaso, Annarita Destro, Jae Yeon Seok, Emanuela Balladore, Luigi Terracciano, Angelo Sangiovanni, Massimo Iavarone, Massimo Colombo, Ja June Jang, Eunsil Yu, So Young Jin, Emanuela Morenghi, Young Nyun Park, Massimo Roncalli
Journal: Journal of Hepatology (2008)
(5) Widespread atypical lichen amyloidosus, primary biliary cirrhosis and scleroderma
Authors: Martin M. Black
Journal: British Journal of Dermatology (1974)

Journal Article (5) Widespread atypical lichen amyloidosus, primary biliary cirrhosis and scleroderma Get access Martin M. Black Martin M. Black St John's Hospital for Diseases of the Skin, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue s10, 1 July 1974, Pages 42–45, https://doi.org/10.1111/j.1365-2133.1974.tb12508.x Published: 01 July 1974
β-Blocker Therapy in Heart Failure
Authors: JoAnne Micale Foody, Michael H Farrell, Harlan M Krumholz
Journal: JAMA (2002)

Care of patients with heart failure has been revolutionized throughout the past decade. A paradigm shift in the strategy for treating heart failure caused by systolic dysfunction is in progress. Despite the initial perception about beta-blockers' safety, they are now the most extensively studied class of agents in the treatment of heart failure and have emerged as an important intervention to improve the clinical outcomes of heart failure patients.To provide scientific rationale for the use of beta-blockers for patients with heart failure.All English-language articles of large, randomized controlled clinical trials assessing the mortality benefits of beta-blockers in patients with heart failure were identified to provide the scientific rationale for the use of beta-blockers in heart failure. Basic science studies were reviewed to provide an overview of the potential physiologic role of beta-blockers in heart failure. Finally, clinical guidelines for the treatment of patients with heart failure were assessed to determine current recommendations for the use of these agents.Randomized controlled clinical trials of beta-blockers that included more than 300 subjects and assessed mortality as a primary end point.Of the 4 beta-blockers tested in large randomized controlled clinical trials of patients with heart failure, 3 are available in the United States, bisoprolol, carvedilol, and metoprolol; 2 of these, carvedilol and metoprolol, have Food and Drug Administration indications for the treatment of heart failure. Compared with placebo treatment, beta-blocker use is associated with a consistent 30% reduction in mortality and a 40% reduction in hospitalizations in patients with class II and III heart failure.Tested in more than 10,000 patients, beta-blockers reduce morbidity and mortality in class II through IV heart failure. Along with angiotensin-converting enzyme inhibitors, digoxin, and diuretics, beta-blockers have strengthened the armamentarium to improve clinical outcomes of heart failure patients. The science supporting beta-blockers must be translated into practice safely and rationally if the agents are to achieve their full potential.
Cutaneous Manifestations of Internal Malignancy
Authors: Bruce H Thiers, Rachel E Sahn, Jeffrey P Callen
Journal: CA A Cancer Journal for Clinicians (2009)

The skin often mirrors changes in the organism it envelops. Many neoplastic diseases that affect internal organs display cutaneous manifestations, which may be the presenting signs and symptoms of the underlying malignancy. These may reflect direct involvement of the skin by the tumor (ie, tumor metastasis) or indirect involvement, in which changes in the skin occur in the absence of malignant cells. This review focuses on the latter conditions, which are often referred to as paraneoplastic dermatoses. Included in the discussion are the cutaneous manifestations of inherited syndromes that are associated with an increased risk of internal malignancy, cutaneous changes in patients with hormone-secreting tumors, and the wide spectrum of proliferative and inflammatory dermatoses that have been associated with internal cancer.
BLM Helicase Complements Disrupted Type II Telomere Lengthening in Telomerase-Negative <i>sgs1</i> Yeast
Authors: Kate Lillard-Wetherell, Kelly A. Combs, Joanna Groden
Journal: Cancer Research (2005)

Abstract Recombination-mediated pathways for telomere lengthening may be utilized in the absence of telomerase activity. The RecQ-like helicases, BLM and Sgs1, are implicated in recombination-mediated telomere lengthening in human cells and budding yeast, respectively. Here, we show that BLM expression rescues disrupted telomere lengthening in telomerase-negative sgs1 yeast. BLM helicase activity is required for this complementation, indicating BLM and Sgs1 resolve the same telomeric structures. These data support a conserved function for BLM and Sgs1 in recombination-mediated telomere lengthening.
5-Methylcytosine hydroxylation-mediated LINE-1 hypomethylation: a novel mechanism of proto-oncogenes activation in colorectal cancer?
Authors: Abbes Belkhiri, Wael El-Rifai
Journal: Gut (2013)

The human genome comprises the most predominant long interspersed nuclear element-1 (LINE-1) sequences, which are non-long-terminal repeat retrotransposons. The majority of LINE-1 repeats are inactivated through truncation, inversion and mutation.1 Importantly, DNA methylation attenuates the transcriptional activation, amplification and recombination of LINE-1 sequences, thereby maintaining genome stability.2 Indeed, global DNA hypomethylation has been associated with increased genomic instability and tumourigenesis, suggesting a more important role for hypomethylation in human cancers than the hypermethylation-induced downregulation of some tumour suppressor genes.3–5 LINE-1 hypomethylation has been shown to associate with the clinicogenetic features of multiple myeloma6 and chronic myeloid leukaemia,7 poor prognosis in non-small cell lung cancer,8 and with more aggressive progression of colorectal cancer (CRC).9

The full-length LINE-1 sequence (6 Kb) includes a sense promoter regulating transcription of two open reading frames and an antisense promoter (ASP) in the 5′-untranslated region, which contains a CpG island—usually hypermethylated in normal cells—regulating transcription of adjacent genes in the opposite direction.10–12 The ASP has been reported to function as an alternative transcription start site for several proto-oncogenes, …
Association of IL-1β (-511 C>T) and IL1RN 86-bp VNTR polymorphism suspectibility with chronic obstrutive pulomary disease between male and female patients in northern Indian population
Authors: Rajni Kant Shukla, Surya Kant, Sandeep Bhattacharya, Balraj Mittal
Journal: European Respiratory Journal (2011)

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic obstruction of expiratory flow affecting peripheral airways, associated with chronic bronchitis (mucus hypersecretion) and emphysema (destruction of airway parenchyma), together with fibrosis, tissue damage and inflammation of the small airways. Interleukin 1 (IL-1) and other cytokines play a central role in chronic inflammatory diseases. our hypothesis is IL-1β (-511C>T) and IL-1RN 86-bp VNTR polymorphism may be associated with COPD susceptibility.

Methodology: A case–control study was performed in 412 subjects (204 COPD patients and 208 healthy controls) to analyze the association of polymorphisms IL-1β (-511C>T) and IL-1RN 86-bp VNTR of genes in susceptibility to COPD in northern Indian population. All subjects were genotyped through polymerase chain reaction and Restriction fragment length polymorphism.

Results: The frequencies of IL-1β (-511C>T) and IL-1RN (variable number tandem repeat) genotypes, alleles, and haplotypes did not differ significantly between patients and controls. However, In IL1 RN allele 1/2 and 2/2 were significant associated with the female COPD patients, with odds ratio [OR] = 2.60; 95% confidence interval [CI] = 1.24-5.44; p=0.011; OR=5.60; 95% CI = 0.95-32.96; p=0.057).

Conclusion: Both the polymorphism IL-1β (-511C>T) and IL1RN showed sex-specific association with COPD in north India.