tbuckley/cabot-search huggingface dataset:
Quantitative Assessment of Angiographic Restenosis After Sirolimus-Eluting Stent Implantation in Native Coronary Arteries
Authors: Jeffrey J. Popma, Martin B. Leon, Jeffrey W. Moses, David R. Holmes, Nicholas Cox, Michelle Fitzpatrick, John Douglas, Charles Lambert, Michael Mooney, Steven Yakubov, Richard E. Kuntz
Journal: Circulation (2004)

Background— Sirolimus-eluting stents (SESs) reduce angiographic restenosis in patients with focal, native coronary artery stenoses. This study evaluated the usefulness of SESs in complex native-vessel lesions at high risk for restenosis. Methods and Results— Angiographic follow-up at 240 days was obtained in 701 patients with long (15- to 25-mm) lesions in small-diameter (2.5- to 3.5-mm) native vessels who were randomly assigned to treatment with SESs or bare-metal stents (BMSs) in the SIRIUS trial. Quantitative angiographic measurements of minimal lumen diameter and percent diameter stenosis were obtained within the treated segment, within the stent, and within its 5-mm proximal and distal edges. Patients treated with SESs had lower rates of binary (&gt;50% diameter stenosis) angiographic restenosis within the segment (8.9% versus 36.3% with the BMS; P &lt;0.001) and within the stent (3.2% versus 35.4% with the BMS; P &lt;0.001). SESs were associated with significantly less late lumen loss within the treated segment, within the stent, and within its 5-mm proximal and distal edges (all P &lt;0.001). The reduction of restenosis with the SES was consistent in patients at risk for restenosis, including those with small vessels, long lesions, and diabetes mellitus. The frequency of late aneurysms was similar in the 2 groups. Conclusions— Compared with BMSs, SESs reduced angiographic late lumen loss within the stent and its adjacent 5-mm margins in patients with complex native-vessel lesions.
Stimulation of mature unprimed CD8+ T cells by semiprofessional antigen-presenting cells in vivo.
Authors: H Kosaka, C D Surh, J Sprent
Journal: The Journal of Experimental Medicine (1992)

To test whether unprimed CD8+ cells can recognize class I alloantigens presented selectively on non-bone marrow (BM)-derived cells, unprimed parental strain CD8+ cells were transferred to long-term parent--&amp;gt;F1 BM chimeras prepared with supralethal irradiation. Host class I expression in the chimeras was undetectable on BM-derived cells and, in spleen, was limited to low-level staining of vascular endothelium and moderate staining of follicular dendritic cells (a population of nonhemopoietic cells in germinal centers). Despite this restricted expression of antigen, acute blood-to-lymph recirculation of parental strain T cells through the chimeras led to selective trapping of 95% of CD8+ cells reactive to normal F1 spleen antigen presenting cells (APC) in vitro. Subsequently, a small proportion of the trapped cells entered cell division and gave rise to effector cells expressing strong host-specific CTL activity. The activation of host-specific CD8+ cells was also prominent in double-irradiated chimeras, and cell separation studies showed that the effector cells were generated from resting precursor cells rather than from memory-phenotype cells. It is suggested that the non-BM-derived cells in the chimeras acted as semiprofessional APC. These cells were nonimmunogenic for most host-reactive CD8+ cells but were capable of stimulating a small subset of high-affinity T cells. The possible relevance of the data to the prolonged immunogenicity of vascularized allografts in humans is discussed.
The incidence of respiratory symptoms and sensitisation in baker apprentices
Authors: T. Skjold, R. Dahl, B. Juhl, T. Sigsgaard
Journal: European Respiratory Journal (2008)

The aim of the current study was to describe the incidence of respiratory symptoms and allergic sensitisation and the sequence of events leading to respiratory symptoms among Danish baker apprentices (BA). A total of 114 BA were surveyed over a 20-month period. Questionnaires were completed along with spirometric analysis and skin-prick tests to common and work-related allergens. Bronchial hyperresponsiveness (BHR) was determined at baseline and at the end of the follow-up period. The incidences of work-related rhinitis and asthma-like symptoms were 22.1 and 10.0 cases.100 person-yrs(-1), respectively. At 20 months the cumulative incidence proportion was 40.2 and 20.5% for rhinitis and asthma-like symptoms, respectively. The cumulative incidence of occupational sensitisation was 6.1%. An increased risk of asthma-like symptoms was found in both atopic subjects and in females. In the BA with new onset respiratory symptoms, an increase in BHR from baseline was observed. Forced expiratory volume in one second and forced vital capacity did not change during the follow-up period. No relationship was observed between new sensitisation and new symptoms. In conclusion rhinitis- and asthma-like symptoms were found to develop commonly in Danish baker apprentices. The mechanism by which symptoms arose was perceived to reflect the development of an inflammation rather than the production of a specific immunoglobulin E pathway, as sensitisation to occupational allergens was rarely observed. Hence, respiratory symptoms and allergy may develop through separate pathways.
Comparative Roles of Microvascular and Nerve Function in Foot Ulceration in Type 2 Diabetes
Authors: Singhan T.M. Krishnan, Neil R. Baker, Anne L. Carrington, Gerry Rayman
Journal: Diabetes Care (2004)

OBJECTIVE—To determine the relative roles of different modalities of sensory nerve function (large and small fiber) and the role of microvascular dysfunction in foot ulceration in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—A total of 20 control subjects and 18 type 2 diabetic subjects with foot ulceration and 20 without were studied. None of the subjects had clinical features of peripheral vascular disease. The Computer-Aided Sensory Evaluator IV (CASE IV) was used to determine vibration detection threshold (VDT), cold detection threshold (CDT), warm detection threshold (WDT), and heat pain onset threshold (HPO). Vibration perception threshold (VPT) was also assessed by a neurothesiometer. Microvascular function (maximum hyperemia to skin heating to 44°C) was assessed using laser Doppler flowmetry (mean maximum hyperemia using laser Doppler flowmeter [LDFmax]), laser Doppler imaging (mean maximum hyperemia using laser Doppler imager [LDImax]), and skin oxygenation with transcutaneous oxygen tension (TcpO2). RESULTS—VPT, VDT, CDT, and HPO were all significantly higher in individuals with ulceration than in those without (VPT and VDT: P &amp;lt; 0.0001) (CDT and HPO: P = 0.01). LDFmax, LDImax, and TcpO2 were significantly lower in the two diabetic groups than in the control subjects, but there was no difference between individuals with and without ulceration. Univariate logistic regression analysis revealed similar odds ratios for foot ulceration for VDT, CDT, HPO, and VPT (OR 1.97 [95% CI 1.30–2.98], 1.58 [1.20–2.08], 2.30 [1.21–4.37], and 1.24 [1.08–1.42], respectively). None of the microvascular parameters yielded significant odds ratios for ulceration. CONCLUSIONS—This study found that there was no additional value in measuring small-fiber function with the CASE IV over measuring vibration by either CASE IV or the inexpensive neurothesiometer in discriminating between individuals with and without ulceration. Furthermore, none of the tests of microvascular function including the TcpO2 were able to discriminate between individuals with and without ulceration, suggesting that such tests may not be of benefit in identifying subjects at greater risk of foot ulceration.
Sustained Inhibition of Angiotensin I–Converting Enzyme (ACE) Expression and Long-Term Antihypertensive Action by Virally Mediated Delivery of ACE Antisense cDNA
Authors: Hongwei Wang, Michael J. Katovich, Craig H. Gelband, Phyllis Y. Reaves, M. Ian Phillips, Mohan K. Raizada
Journal: Circulation Research (1999)

Abstract —Angiotensin I–converting enzyme (ACE) inhibitors have been proven to be highly effective and are for the most part the drugs of choice in the treatment and control of hypertension, congestive heart failure, and left ventricular dysfunction. Despite this, questions regarding side effects and compliance with this traditional pharmacological strategy remain. In view of these observations, coupled with recent advances in gene-transfer technology, our objective in this study was to determine whether the expression of ACE could be controlled on a permanent basis at a genetic level. We argued that the introduction of ACE antisense to inhibit the enzyme would be a prerequisite in considering the antisense gene therapy for the control of hypertension and other related pathological states. Retroviral vectors (LNSV) containing ACE sense (LNSV-ACE-S) and ACE antisense (LNSV-ACE-AS) sequences were constructed and were used in rat pulmonary artery endothelial cells (RPAECs) to determine the feasibility of this approach. Infection of rat RPAECs with LNSV-ACE-S and LNSV-ACE-AS resulted in a robust expression of transcripts corresponding to ACE-S and ACE-AS, respectively, for the duration of these experiments, ie, 8 consecutive passages. The expression of ACE-AS but not of ACE-S was associated with a permanent decrease of ≈70% to 75% in ACE expression and a 50% increase in the B max for the AT 1 s. Although angiotensin II caused a concentration-dependent stimulation of intracellular Ca 2+ levels in both ACE-S– and ACE-AS–expressing cells, the stimulation was significantly higher in ACE-AS–expressing RPAECs. In vivo experiments demonstrated a prolonged expression of ACE-AS transcripts in cardiovascularly relevant tissues of rats. This was associated with a long-term reduction in blood pressure by ≈15 mm Hg, exclusively in the spontaneously hypertensive rat. These observations demonstrate that delivery of ACE-AS by retroviral vector results in a permanent inhibition of ACE and a long-term reduction in high blood pressure in the spontaneously hypertensive rat.
Intrarenal Injection of Bone Marrow-Derived Angiogenic Cells Reduces Endothelial Injury and Mesangial Cell Activation in Experimental Glomerulonephritis
Authors: Hideki Uchimura, Takeshi Marumo, Osamu Takase, Hiroshi Kawachi, Fujio Shimizu, Matsuhiko Hayashi, Takao Saruta, Keiichi Hishikawa, Toshiro Fujita
Journal: Journal of the American Society of Nephrology (2005)

Loss of glomerular endothelial cells has been suggested to contribute to the progression of glomerular injury. Although therapeutic angiogenesis induced by administration of bone marrow-derived endothelial progenitor cells has been observed in disease models of endothelial injury, the effects on renal disease have not been clarified. Whether administration of culture-modified bone marrow mononuclear cells would mitigate the glomerular endothelial injury in anti-Thy1.1 nephritis was investigated. After cultivation under conditions that promote endothelial progenitor cell growth, bone marrow mononuclear cells were labeled with CM-DiI, a fluorescence marker, and injected into the left renal artery of Lewis rats with anti-Thy1.1 glomerulonephritis. The decrease in glomerular endothelial cells was significantly attenuated in the left kidney, as compared with the right, in nephritic rats that received the cell infusion. Glomerular injury score, the area positive for mesangial alpha-smooth muscle actin, and infiltration of macrophages were significantly decreased in the left kidney. CM-DiI-positive cells were distributed in glomeruli of the left kidney but not in those of the right kidney. Among CM-DiI-labeled cells incorporated into glomeruli, 16.5 +/- 1.2% of cells were stained with an endothelial marker, rat endothelial cell antigen-1. Culture-modified mononuclear cells secreted 281.2 +/- 85.0 pg of vascular endothelial growth factor per 10(5) cells per day. In conclusion, intra-arterial administration of culture-modified bone marrow mononuclear cells reduced endothelial injury and mesangial activation in anti-Thy1.1 glomerulonephritis. Incorporation into the glomerular endothelial lining and production of angiogenic factor(s) are likely to contribute to the protective effects of culture-modified mononuclear cells against glomerular injury.
Cardiovascular and metabolic risks in psoriasis and psoriatic arthritis: pragmatic clinical management based on available evidence: Table 1
Authors: Hanna Johnsson, Iain B McInnes, Naveed Sattar
Journal: Annals of the Rheumatic Diseases (2012)

Several studies suggest that patients with psoriasis and, in particular, psoriatic arthritis (PsA) are at increased risk of cardiovascular disease. These patients are also more likely to be obese and to have diabetes and fatty liver disease. This article discusses the association between psoriasis and PsA and cardiometabolic disorders, emphasising the need for better consideration of simple lifestyle interventions. It also highlights areas for future research and proposes a simple and pragmatic test portfolio to screen for cardiovascular risk and metabolic disorders in patients at higher risk.
Cd40–Cd40 Ligand Interactions in Vivo Regulate Migration of Antigen-Bearing Dendritic Cells from the Skin to Draining Lymph Nodes
Authors: Angus M. Moodycliffe, Vijay Shreedhar, Stephen E. Ullrich, Jeffrey Walterscheid, Corazon Bucana, Margaret L. Kripke, Leopoldo Flores-Romo
Journal: The Journal of Experimental Medicine (1999)

Whereas CD40-CD40 ligand interactions are important for various dendritic cell (DC) functions in vitro, their in vivo relevance is unknown. We analyzed the DC status of CD40 ligand -/- mice using a contact hypersensitivity (CHS) model system that enables multiple functions of DCs to be assessed in vivo. Immunohistochemistry of skin sections revealed no differences in terms of numbers and morphology of dendritic epidermal Langerhans cells (LCs) in unsensitized CD40 ligand -/- mice as compared with wild-type C57BL/6 mice. However, after contact sensitization of CD40 ligand -/- mice, LCs failed to migrate out of the skin and substantially fewer DCs accumulated in draining lymph nodes (DLNs). Furthermore, very few antigen-bearing DCs could be detected in the paracortical region of lymph nodes draining sensitized skin. This defect in DC migration after hapten sensitization was associated with defective CHS responses and decreased cutaneous tumor necrosis factor (TNF)-alpha production and was corrected by injecting recombinant TNF-alpha or an agonistic anti-CD40 monoclonal antibody. Thus, CD40-CD40 ligand interactions in vivo regulate the migration of antigen-bearing DCs from the skin to DLNs via TNF-alpha production and play a vital role in the initiation of acquired T cell-mediated immunity.
Patient-Derived First Generation Xenografts of Non–Small Cell Lung Cancers: Promising Tools for Predicting Drug Responses for Personalized Chemotherapy
Authors: Xin Dong, Jun Guan, John C. English, Julia Flint, John Yee, Kenneth Evans, Nevin Murray, Calum MacAulay, Raymond T. Ng, Peter W. Gout, Wan L. Lam, Janessa Laskin, Victor Ling, Stephen Lam, Yuzhuo Wang
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Current chemotherapeutic regimens have only modest benefit for non–small cell lung cancer (NSCLC) patients. Cumulative toxicities/drug resistance limit chemotherapy given after the first-line regimen. For personalized chemotherapy, clinically relevant NSCLC models are needed for quickly predicting the most effective regimens for therapy with curative intent. In this study, first generation subrenal capsule xenografts of primary NSCLCs were examined for (a) determining responses to conventional chemotherapeutic regimens and (b) selecting regimens most effective for individual patients. Experimental Design: Pieces (1×3×3 mm3) of 32 nontreated, completely resected patients' NSCLCs were grafted under renal capsules of nonobese diabetic/severe combined immunodeficient mice and treated with (A) cisplatin+vinorelbine, (B) cisplatin+docetaxel, (C) cisplatin+gemcitabine, and positive responses (treated tumor area ≤50% of control, P &amp;lt; 0.05) were determined. Clinical outcomes of treated patients were acquired. Results: Xenografts from all NSCLCs were established (engraftment rate, 90%) with the retention of major biological characteristics of the original cancers. The entire process of drug assessment took 8 weeks. Response rates to regimens A, B, and C were 28% (9 of 32), 42% (8 of 19), and 44% (7 of 16), respectively. Certain cancers that were resistant to a particular regimen were sensitive to others. The majority of responsive tumors contained foci of nonresponding cancer cells, indicative of tumor heterogeneity and potential drug resistance. Xenografts from six of seven patients who developed recurrence/metastasis were nonresponsive. Conclusions: Models based on first generation NSCLC subrenal capsule xenografts have been developed, which are suitable for quick assessment (6-8 weeks) of the chemosensitivity of patients' cancers and selection of the most effective regimens. They hold promise for application in personalized chemotherapy of NSCLC patients. Clin Cancer Res; 16(5); 1442–51
Statins Promote Potent Systemic Antioxidant Effects Through Specific Inflammatory Pathways
Authors: Mehdi H. Shishehbor, Marie-Luise Brennan, Ronnier J. Aviles, Xiaoming Fu, Marc S. Penn, Dennis L. Sprecher, Stanley L. Hazen
Journal: Circulation (2003)

Background— The pleiotropic actions of hydroxymethylglutaryl CoA reductase inhibitors (statins) include antiinflammatory and antioxidant actions. We recently reported that statins induce reductions in plasma protein levels of nitrotyrosine (NO 2 Tyr), a modification generated by nitric oxide–derived oxidants. Whether alternative oxidative pathways are suppressed in vivo after statin administration has not yet been reported. Methods and Results— As an extension of our prior study, hypercholesterolemic subjects with no known coronary artery disease were evaluated at baseline and after 12 weeks of atorvastatin therapy (10 mg/d). Plasma levels of protein-bound chlorotyrosine, NO 2 Tyr, dityrosine, and orthotyrosine, specific molecular fingerprints for distinct oxidative pathways upregulated in atheroma, were determined by mass spectrometry. In parallel, alterations in lipoproteins and C-reactive protein were determined. Statin therapy caused significant reductions in chlorotyrosine, NO 2 Tyr, and dityrosine (30%, 25%, and 32%, respectively; P &lt;0.02 each) that were similar in magnitude to reductions in total cholesterol and apolipoprotein B-100 (25% and 29%, P &lt;0.001 each). Nonsignificant decreases in orthotyrosine and C-reactive protein levels were observed (9% and 11%, respectively; P &gt;0.10 each). Statin-induced reductions in oxidation markers were independent of decreases in lipids and lipoproteins. Conclusions— Statins promote potent systemic antioxidant effects through suppression of distinct oxidation pathways. The major pathways inhibited include formation of myeloperoxidase-derived and nitric oxide–derived oxidants, species implicated in atherogenesis. The present results suggest potential mechanisms that may contribute to the beneficial actions of statins. They also have important implications for monitoring the antiinflammatory and antioxidant actions of these agents.
MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study
Authors: Charles Peterfy, Paul Emery, Paul P Tak, Mikkel Østergaard, Julie DiCarlo, Kati Otsa, Federico Navarro Sarabia, Karel Pavelka, Marie-Agnes Bagnard, Lykke Hinsch Gylvin, Corrado Bernasconi, Annarita Gabriele
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. <h3>Methods</h3> Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52. The primary end point was the change in MRI erosion score from baseline at week 24. <h3>Results</h3> Patients treated with rituximab demonstrated significantly less progression in the mean MRI erosion score compared with those treated with placebo at weeks 24 (0.47, 0.18 and 1.60, respectively, p=0.003 and p=0.001 for the two rituximab doses vs placebo) and 52 (−0.30, 0.11 and 3.02, respectively; p&lt;0.001 and p&lt;0.001). Cartilage loss at 52 weeks was significantly reduced in the rituximab group compared with the placebo group. Other secondary end points of synovitis and osteitis improved significantly with rituximab compared with placebo as early as 12 weeks and improved further at weeks 24 and 52. <h3>Conclusions</h3> This study demonstrated that rituximab significantly reduced erosion and cartilage loss at week 24 and week 52 in MTX-inadequate responder patients with active RA, suggesting that MRI is a valuable tool for assessing inflammatory and structural damage in patients with established RA receiving rituximab. <h3>Trial registration number</h3> NCT00578305
The impact of acute kidney injury in cirrhosis: does definition matter?: Table 1
Authors: Alexander L Gerbes
Journal: Gut (2013)

The impact of acute kidney injury in cirrhosis: does definition matter?In their important study, Tsien et al 1 demonstrated for the first time that minor increases of serum creatinine have major clinical impact in outpatients with cirrhosis, ascites and normal serum creatinine.Patients with acute kidney injury (AKI) had a slow constant increase of serum creatinine over time and, interestingly, a reduced survival probability.These data support the concept that not only hepatorenal syndrome, but also minor changes of normal serum creatinine may have clinical importance. 2 3 However, no predictors of reversal of AKI could be identified.Possibly, more sensitive markers of reduced glomerular filtration rate, such as cystatin C 4 or NGAL, 5 may be suitable predictors.Another aspect of AKI remains to be elucidated: AKI stage 1 is defined by an increase of serum creatinine of at least 50% or 0.3 mg/dl over serum baseline.These changes, however, may denote different changes of creatinine, as illustrated in table 1, and consequently, even more marked differences of creatinine clearance.Patients with a serum creatinine >0.6 mg/dl do exhibit a more marked increase of creatinine when AKI is defined by a 50% rise.For instance, with a baseline creatinine of 1.0 mg/dl AKI may be reached when creatinine rises to 1.3 mg/dl or to 1.5 mg/dl depending on the definition used.Thus, it may be worthwhile to analyse the data of Wong et al with the hypothesis, that AKI defined by a 50% increase discriminates even more clearly between survivors and non-survivors, and may be a predictor of non-reversal of AKI.
Determinants of protein function revealed by combinatorial entropy optimization
Authors: Boris Reva, Yevgeniy Antipin, Chris Sander
Journal: Genome biology (2007)

We use a new algorithm (combinatorial entropy optimization [CEO]) to identify specificity residues and functional subfamilies in sets of proteins related by evolution. Specificity residues are conserved within a subfamily but differ between subfamilies, and they typically encode functional diversity. We obtain good agreement between predicted specificity residues and experimentally known functional residues in protein interfaces. Such predicted functional determinants are useful for interpreting the functional consequences of mutations in natural evolution and disease.