tbuckley/cabot-search huggingface dataset:
Oxidative stress and airway inflammation in severe exacerbations of COPD
Authors: E M Drost
Journal: Thorax (2005)

A study was undertaken to assess both oxidative stress and inflammation in the lungs of patients with chronic obstructive pulmonary disease (COPD) during severe and very severe exacerbations compared with those with stable COPD, healthy smokers, and non-smokers. Two sites within the lungs were compared: the large airways (in sputum) and the peripheral airways (by bronchoalveolar lavage (BAL)).BAL fluid cell numbers and levels of tumour necrosis factor (TNFalpha) and interleukin (IL)-8 were measured as markers of airway inflammation and glutathione (GSH) levels as a marker of antioxidant status. Nuclear translocation of the pro-inflammatory transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) were also measured by electromobility shift assay in BAL fluid leucocytes and lung biopsy samples.Influx of inflammatory cells into the peripheral airways during exacerbations of COPD was confirmed. Increased IL-8 levels were detected in BAL fluid from patients with stable COPD compared with non-smokers and healthy smokers, with no further increase during exacerbations. In contrast, IL-8 levels in the large airways increased during exacerbations. GSH levels were increased in the BAL fluid of smokers (444%) and patients with stable COPD (235%) compared with non-smokers and were reduced during exacerbations (severe 89.2%; very severe 52.3% compared with stable COPD). NF-kappaB DNA binding in BAL leucocytes was decreased in healthy smokers compared with non-smokers (41.3%, n = 9, p<0.001) but did not differ in COPD patients, whereas AP-1 DNA binding was significantly decreased during exacerbations of COPD.There is evidence of increased oxidative stress in the airways of patients with COPD that is increased further in severe and very severe exacerbations of the disease. This is associated with increased neutrophil influx and IL-8 levels during exacerbations.
Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial
Authors: Iain B McInnes, Arthur Kavanaugh, Alice B Gottlieb, Lluís Puig, Proton Rahman, Christopher Ritchlin, Carrie Brodmerkel, Shu Li, Yuhua Wang, Alan M Mendelsohn, Mittie K Doyle
Journal: The Lancet (2013)
Molecular Pathways: Hypoxia Response in Immune Cells Fighting or Promoting Cancer
Authors: Asis Palazón, Julián Aragonés, Aizea Morales-Kastresana, Manuel Ortiz de Landázuri, Ignacio Melero
Journal: Clinical Cancer Research (2011)

Both malignant and stromal components in tumors are influenced by the physiologic conditions of the microenvironment. Hypoxia is a prominent feature of solid tumors as a result of defective vascularization and intense metabolic activity. The gene-expression control mechanisms that adapt tissues to hypoxia are exploited by tumors to promote angiogenesis and vasculogenesis. The functions of infiltrating immune cells (macrophages and lymphocytes) and other stromal components are also influenced by a limited O(2) supply. Hypoxia-inducible factors (HIF) are the main molecular transcriptional mediators in the hypoxia response. The degradation and activity of HIF-1α and HIF-2α are tightly controlled by the fine-tuned action of oxygen-sensing prolyl and asparaginyl hydroxylase enzymes. Recent evidence indicates that hypoxia can modulate the differentiation and function of T lymphocytes and myeloid cells, skewing their cytokine-production profiles and modifying the expression of costimulatory receptors. This conceivably includes tumor-infiltrating lymphocytes. Hypoxia not only directly affects tumor-infiltrating leukocytes but also exerts effects on tumor cells and vascular cells that indirectly cause selective chemokine-mediated recruitment of suppressive and proangiogenic T-cell subsets. This review focuses on changes induced by hypoxia in immune cells infiltrating solid malignancies. Such changes may either promote or fight cancer, and thus are important for immunotherapy.
The Assessment in Spondyloarthritis International Society (ASAS) classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general: the spondyloarthritis concept in progress
Authors: H. Zeidler, B. Amor
Journal: Annals of the Rheumatic Diseases (2010)

The unifying concept initially termed seronegative spondarthritides , which first lumped together an interrelated yet heterogeneous group of disorders, was a pivotal step forward in the modern classification of rheumatic conditions.1 However, classification of rheumatic diseases has evolved over the years following progress in knowledge of the clinical features, genetic predisposition, pathophysiology and aetiology of the various disorders. In this issue, Rudwaleit and colleagues2 present new Assessment in Spondyloarthritis International Society (ASAS) classification criteria for peripheral spondyloarthritis (SpA) ( see article on page 15 ). We will discuss the implication of this new set of classification criteria in view of the history and present state of the concept and terminology of SpA, the controversy of lumping and splitting, and the potential for the future use of the new criteria in research and clinical practice. Additionally, we put into perspective the recent elucidation of the frequency of chlamydial infections in undifferentiated SpA (uSpA) and the potential for their cure with combination antibiotic treatment, which might have implications for future classification of SpAs.

The first classification criteria for ankylosing spondylitis (AS) were proposed in 1963 at the European Congress of Rheumatology in Rome based on the clinical experience of European rheumatologists, who viewed AS a disease entity separate from rheumatoid arthritis (RA), in contrast to US rheumatologists, who described rheumatoid spondylitis as a variant of RA.3 As the seminal event in the early 1970s, however, Moll et al 1 formulated the unified concept of seronegative polyarthritis, which they termed seronegative spondarthritides under consideration, the prefix ‘spond-’emphasising the strong association between each member of the group and AS. The diseases initially included were AS, psoriatic disease, Reiter's syndrome, the arthropathies of ulcerative colitis and Crohn's disease, Whipple's disease and Behcet syndrome with the suggested common characteristics: absence of rheumatoid factors, absence of …
Phase I Study of Vorinostat in Combination with Temozolomide in Patients with High-Grade Gliomas: North American Brain Tumor Consortium Study 04-03
Authors: Eudocia Q. Lee, Vinay K. Puduvalli, Joel M. Reid, John G. Kuhn, Kathleen R. Lamborn, Timothy F. Cloughesy, Susan M. Chang, Jan Drappatz, W. K. Alfred Yung, Mark R. Gilbert, H. Ian Robins, Frank S. Lieberman, Andrew B. Lassman, Renee M. McGovern, Jihong Xu, Serena Desideri, Xiabu Ye, Matthew M. Ames, Igor Espinoza-Delgado, Michael D. Prados, Patrick Y. Wen
Journal: Clinical Cancer Research (2012)

A phase I, dose-finding study of vorinostat in combination with temozolomide (TMZ) was conducted to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with high-grade glioma (HGG).This phase I, dose-finding, investigational study was conducted in two parts. Part 1 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days every 28 days. Part 2 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days of the first cycle and 200 mg/m(2)/day for 5 days of the subsequent 28-day cycles.In part 1, the MTD of vorinostat administered on days 1 to 7 and 15 to 21 of every 28-day cycle, in combination with TMZ, was 500 mg daily. Dose-limiting toxicities (DLT) included grade 3 anorexia, grade 3 ALT, and grade 5 hemorrhage in the setting of grade 4 thrombocytopenia. In part 2, the MTD of vorinostat on days 1 to 7 and 15 to 21 of every 28-day cycle, combined with TMZ, was 400 mg daily. No DLTs were encountered, but vorinostat dosing could not be escalated further due to thrombocytopenia. The most common serious adverse events were fatigue, lymphopenia, thrombocytopenia, and thromboembolic events. There were no apparent pharmacokinetic interactions between vorinostat and TMZ. Vorinostat treatment resulted in hyperacetylation of histones H3 and H4 in peripheral mononuclear cells.Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway.
Plasma Concentration of C-Reactive Protein and the Calculated Framingham Coronary Heart Disease Risk Score
Authors: Michelle A. Albert, Robert J. Glynn, Paul M Ridker
Journal: Circulation (2003)

Although C-reactive protein (CRP) predicts vascular risk, few data are available evaluating the relation between CRP and the Framingham Coronary Heart Disease Risk Score (FCRS).CRP levels were compared with calculated 10-year FCRS in a cross-sectional survey of 1666 individuals free of cardiovascular disease. Among men and women not using hormone replacement therapy (HRT), CRP levels were significantly related to 10-year Framingham Coronary Heart Disease Risk categories [total cholesterol (TC) score for men and women: r=0.29 and r=0.22, respectively; LDL cholesterol score for men and women: r=0.29 and r=0.22, respectively, all probability values <0.01]. However, CRP levels correlated minimally with individual components of the FCRS, which included age (r(men)=0.17, r(women)=-0.003), TC (r(men)=-0.02, r(women)=-0.006), HDL-C (r(men)=0.13), LDL-C (r(men)=-0.0002, r(women)=0.012), blood pressure (rmen=0.18, r(women)=0.22), diabetes (r(men)=0.10, r(women)=0.07), and smoking (r(men)=0.16, r(women)=0.14) status. For women taking HRT, no significant relation was observed between CRP and the FCRS, although the power to detect effects in this subgroup is limited.Our data demonstrate that CRP levels significantly correlate with calculated 10-year Framingham Coronary Heart Disease Risk in men and women not taking HRT but correlate minimally with most individual components of the FCRS. These data provide additional support for continued evaluation of CRP as a potential adjunct in the global prediction of cardiovascular risk.
Murine Natural Antitumor Antibodies. III. Interferon Treatment of a Natural Killer-Resistant Lymphoma: Augmentation of Natural Antibody Reactivity and Susceptibility to In Vivo Natural Resistance&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: V E Miller, B Pohajdak, A H Greenberg
Journal: JNCI Journal of the National Cancer Institute (1983)

Treatment of a natural killer cell-resistant (NKR) DBA/2 lymphoma with L-cell interferon (IFN) enhanced its reactivity to serum natural antibody in vitro in cytolysis and absorption studies and increased the in vivo acquisition of natural and antitumor antibody in the peritoneal cavity. The IFN effects were both time- and dose-dependent. In vitro IFN-treated, [131I]5-iodo-2′-deoxyuridine-labeled tumor cells, when injected ip into normal syngeneic mice, were more rapidly eliminated than were untreated control cells. IFN treatment of the NKR tumor decreased “cold-target” inhibition of NK lysis and did not alter binding or lysis by macrophages. These findings indicated that the enhancement of natural resistance to the IFN-treated tumor did not involve NK cells or macrophages and suggested that IFN may enhance host antitumor resistance by increasing tumor reactivity to antibody.
Relationship of the constituents of bile to biliary peritonitis in the rat.
Authors: E M Walker, H Ellis
Journal: Gut (1978)

The local action of bile salts has been associated with a wide variety of gastrointestinal diseases. This paper describes an animal model to determine which of the major solid components of bile are responsible for peritoneal destruction in biliary peritonitis. In the rat, bile salts within the peritoneal cavity cause peritonitis but cholesterol and lecithin are without deleterious effect.
Ammonium Handling by Superficial and Juxtamedullary Nephrons in the Rat
Authors: John Buerkert, Daniel Martin, David Trigg
Journal: Journal of Clinical Investigation (1982)

Papillary and surface micropuncture was used to assess the effects of a chronic metabolic acidosis on the renal tubular handling of ammonium by surface nephrons, juxtamedullary nephrons, and the terminal segment of collecting duct. Rats chronically fed ammonium chloride had an expected decline in arterial pH and bicarbonate concentration associated with a doubling in the amount of ammonium excreted and a decline in urine pH. The glomerular filtration rate and absolute delivery of water and sodium to micropuncture sites of surface and deep nephrons was not measurably altered. Ammonium delivery to the end of the proximal tubule increased from 853±102% to 1,197±142% (SE) of the filtered load of ammonium after the induction of metabolic acidosis. This increase was due to a rise in tubular fluid ammonium content from 2.31±0.23 to 4.06±0.28 mM/liter. After the induction of acidosis, absolute and fractional delivery of ammonium ion to the end of the distal tubule was less than to the end of the accessible portion of the proximal tubule. These findings indicate that ammonium is lost in the intervening segment.
Skin care in the aging female: myths and truths
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2012)

I recently had the opportunity to visit a very relaxing and beautiful day spa during the middle-of-the-day break from the sessions at a Keystone meeting. I was having a very tranquil and restorative day, when I went in for my final treatment - a facial. The very chipper and cheerful esthetician began examining my skin and applying various creams, when I then heard her say something that nearly ruined my experience: she claimed that the topical treatment she was about to apply would, in her words, "cleanse my liver."
The Promise of Combining Inhibition of PI3K and PARP as Cancer Therapy
Authors: Farah L. Rehman, Christopher J. Lord, Alan Ashworth
Journal: Cancer Discovery (2012)

Abstract Analyses of in vitro and patient-derived in vivo models of breast cancer reveal that a combination of inhibitors of the enzymes PARP and phosphoinositide 3-kinase (PI3K) is a potentially effective treatment regimen for breast cancer tumors with elevated activity of the PI3K pathway. Cancer Discov; 2(11); 982–4. ©2012 AACR. Commentary on Ibrahim et al., p. 1036. Commentary on Juvekar et al., p. 1048.
THE ABIOTIC ACTION OF ULTRA-VIOLET LIGHT
Authors: H. S. Newcomer
Journal: The Journal of Experimental Medicine (1917)

Typhoid bacilli are about one two-hundredth as sensitive to ultraviolet light of wave-lengths 2100 to 2800 Angström units as is the photographic plate. This sensitivity then falls off, decreasing rapidly to almost zero sensitivity at about 2970, the beginning of the sun's spectrum.
Discrimination of Human Lung Neoplasm from Normal Lung by Two Target Genes
Authors: Hans-Stefan Hofmann, Gesine Hansen, Stefan Burdach, Babett Bartling, Rolf-Edgar Silber, Andreas Simm
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Simple tools for discrimination of lung tissues can be useful in a fast machine-aided diagnosis, for example, by tumor-specific microarrays. We demonstrate that an easy ratio technique, based on the expression levels of only two genes differentially expressed in lung tumor and normal lung samples, allows discrimination of normal and neoplastic lung with a sensitivity of 100% and specificity of 90.5%. DNA microarray analysis of 99 lung tumor samples and 15 normal lung tissues revealed that receptor for advanced glycation end products (RAGE) mRNA is reduced fourfold (p = 7.8 x 10(-11)) and cyclin-B2 mRNA is upregulated twofold (p = 5.9 x 10(-18)) in lung carcinoma compared with normal lung. The microarray-calculated expression ratio of RAGE to cyclin-B2 was used in polymerase chain reaction analysis of 84 independent blinded samples to discriminate tumor and corresponding normal lung tissues. In 94.7% of the samples this quotient correctly distinguished non-small cell lung cancer from normal lung tissue, suggesting the RAGE/cyclin-B2 quotient as a potential means for diagnosis of lung cancer.
Factors influencing the decline in lung density in a Danish lung cancer screening cohort
Authors: Saher B. Shaker, Asger Dirksen, Pechin Lo, Lene T. Skovgaard, Marleen de Bruijne, Jesper H. Pedersen
Journal: European Respiratory Journal (2012)

Lung cancer screening trials provide an opportunity to study the natural history of emphysema by using computed tomography (CT) lung density as a surrogate parameter. In the Danish Lung Cancer Screening Trial, 2,052 participants were included. At screening rounds, smoking habits were recorded and spirometry was performed. CT lung density was measured as the volume-adjusted 15th percentile density (PD15). A mixed effects model was used with former smoking males with &lt;30 pack-yrs and without airflow obstruction (AFO) at entry as a reference group. At study entry, 893 (44%) participants had AFO. For the reference group, PD15 was 72.6 g·L −1 with an annual decline of -0.33 g·L −1 . Female sex and current smoking increased PD15 at baseline, 17.3 g·L −1 (p&lt;0.001) and 10 g·L −1 (p&lt;0.001), respectively; and both increased the annual decline in PD15 (female: -0.3 g·L −1 ; current smoking: -0.4 g·L −1 ). The presence and severity of AFO was a strong predictor of low PD15 at baseline (Global Initiative for Chronic Obstructive Lung Disease (GOLD) I: -1.4 g·L −1 ; GOLD II: -6.3 g·L −1 ; GOLD III: -17 g·L −1 ) and of increased annual decline in PD15 (GOLD I: -0.2 g·L −1 ; GOLD II: -0.5 g·L −1 ; GOLD III: -0.5 g·L −1 ). Female sex, active smoking and the presence of AFO are associated with accelerated decline in lung density.
Extent and Consequences of Antibody Formation Against Adalimumab in Patients With Psoriasis
Authors: Stef P. Menting, Paula P. M. van Lümig, Anna-Christa Q. de Vries, Juul M. P. A. van den Reek, Desiree van der Kleij, Elke M. G. J. de Jong, Phyllis I. Spuls, Lidian L. A. Lecluse
Journal: JAMA Dermatology (2013)

In a previously reported cohort of 29 patients with plaque-type psoriasis followed up for 24 weeks, clinically relevant antidrug antibody (ADA) to adalimumab was frequently found. Long-term data were lacking. We now present the extension of this study: 80 patients followed up for 1 year.To assess the extent of ADA and its clinical consequences after 24 weeks of adalimumab treatment for psoriasis in a cohort of 80 patients.A multicenter cohort study, performed in the outpatient dermatology clinic of 2 academic hospitals, included 80 sequential patients receiving adalimumab therapy for plaque-type psoriasis and had a follow-up of 1 year. Outcome assessors were not aware of the presence of antibodies to adalimumab or the adalimumab serum concentration when assessing patients' Psoriasis Area and Severity Index (PASI), and personnel analyzing serum samples were blinded to patients' PASI.For 80 patients treated with adalimumab for psoriasis, disease severity (PASI) was assessed, blood samples were collected, and adalimumab and ADA concentrations was determined at baseline and at weeks 12, 24, and 52.Patient PASI and adalimumab and ADA concentrations.Antidrug antibody formed in 49% of patients, before week 24 in 90% of them. Adalimumab and ADA concentrations, clinical response and ADA concentration, and adalimumab concentration and clinical response had correlations of -0.872, -0.606, and 0.519, respectively. The adalimumab dose interval was shortened because of lack of efficacy in 15 patients, 7 with and 8 without ADA; improvement in responder status occurred in 1 of 7 and 4 of 8, respectively.Patients with no ADA formation in the first 24 weeks of treatment have little chance of it in the following 24 weeks. The presence of ADA is strongly correlated with adalimumab concentration and greatly influences clinical response. If ADA is present, dose interval shortening is less useful.
Radioimmunotherapy for Colorectal Cancer
Authors: Monica M. Bertagnolli
Journal: Clinical Cancer Research (2005)

Monoclonal antibodies, selected for their ability to recognize and bind tumor-specific antigens, are a promising vehicle for systemic antitumor therapy. Radioimmunotherapy utilizes radioisotopes conjugated to monoclonal antibodies to deliver tumoricidal radiation doses. In the >20 years since
Prevalence and Correlates of Depression in Individuals With and Without Type 1 Diabetes
Authors: Nicole Gendelman, Janet K. Snell-Bergeon, Kim McFann, Gregory Kinney, R. Paul Wadwa, Franziska Bishop, Marian Rewers, David M. Maahs
Journal: Diabetes Care (2009)

OBJECTIVE Depression is associated with poor glycemic control and complications in people with type 1 diabetes. We assessed the prevalence of depression and antidepressant medication use among adults with and without type 1 diabetes and the association between depression and diabetes complications. RESEARCH DESIGN AND METHODS In 2006–2008, the Coronary Artery Calcification in Type 1 Diabetes Study applied the Beck Depression Inventory II (BDI-II) to 458 participants with type 1 diabetes (47% male, aged 44 ± 9 years, type 1 diabetes duration 29 ± 9 years) and 546 participants without diabetes (nondiabetic group) (51% male, aged 47 ± 9 years). Use of antidepressant medication was self-reported. Depression was defined as a BDI-II score &amp;gt;14 and/or use of antidepressant medication. Occurrence of diabetes complications (retinopathy, blindness, neuropathy, diabetes-related amputation, and kidney or pancreas transplantation) was self-reported. RESULTS Mean BDI-II score, adjusted for age and sex, was significantly higher in participants with type 1 diabetes than in nondiabetic participants (least-squares mean ± SE: 7.4 ± 0.3 vs. 5.0 ± 0.3; P &amp;lt; 0.0001). Type 1 diabetic participants reported using more antidepressant medications (20.7 vs. 12.1%, P = 0.0003). More type 1 diabetic than nondiabetic participants were classified as depressed by BDI-II cut score (17.5 vs. 5.7%, P &amp;lt; 0.0001) or by either BDI-II cut score or antidepressant use (32.1 vs. 16.0%, P &amp;lt; 0.0001). Participants reporting diabetes complications (n = 209) had higher mean BDI-II scores than those without complications (10.7 ± 9.3 vs. 6.4 ± 6.3, P &amp;lt; 0.0001). CONCLUSIONS Compared with nondiabetic participants, adults with type 1 diabetes report more symptoms of depression and more antidepressant medication usage. Depression is highly prevalent in type 1 diabetes and requires further study on assessment and treatment.