tbuckley/cabot-search huggingface dataset:
Lanreotide Reduces Serum Free and Total Insulin-Like Growth Factor-I After Angioplasty
Authors: Jan Frystyk, Christian Skjærbæk, Niels Alexander, Håkan Emanuelsson, Harry Suryapranata, Horst Beyer, Marie Foegh, Hans Ørskov
Journal: Circulation (1996)

Background Several experiments point to a participating role of insulin-like growth factor-I (IGF-I) in the vascular events leading to restenosis after percutaneous transluminal coronary angioplasty (PTCA). Methods and Results We measured fasting serum total (extractable) IGF-I in 553 patients in a controlled clinical trial. Half of the patients received continuous subcutaneous infusion of the somatostatin analogue lanreotide from the day before (baseline) and for 4 days after PTCA. We also measured ultrafiltrated serum free IGF-I and IGF-II, total IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-3, and insulin in a subgroup of 18 placebo-treated and 20 lanreotide-treated patients. Total IGF-I had decreased by 7% ( P &lt;.0001) 1 day after initiation of lanreotide infusion and stayed reduced, whereas no early changes occurred in placebo-treated patients. The same pattern was observed in the subgroup. Free IGF-I decreased significantly from baseline by 22% to 27% ( P &lt;.05) in lanreotide-treated patients and increased insignificantly by 10% to 30% ( P =.054) in placebo-treated patients. IGFBP-1 increased ( P &lt;.05) in both groups postoperatively, but levels in lanreotide-treated patients exceeded ( P &lt;.05) those of placebo-treated patients. Lanreotide treatment resulted in minor reductions ( P &lt;.05) in free and total IGF-II and IGFBP-3, whereas insulin was unaltered. Conclusions Lanreotide administration acutely decreases circulating total and free IGF-I, the latter relatively more, and increases IGFBP-1. These alterations in the IGF system may participate in the improvement of the long-term outcome after PTCA noted with lanreotide treatment.
Targeting Cancer-Derived Adenosine:New Therapeutic Approaches
Authors: Arabella Young, Deepak Mittal, John Stagg, Mark J. Smyth
Journal: Cancer Discovery (2014)

CD73 generation of immunosuppressive adenosine within the hypoxic tumor microenvironment causes dysregulation of immune cell infiltrates, resulting in tumor progression, metastases, and poor disease outcomes. Therapies targeted toward the adenosinergic pathway, such as antibodies targeting CD73 and CD39, have proven efficacy in mouse tumor models; however, humanized versions are only in preliminary development. In contrast, A(2A) adenosine receptor antagonists have progressed to late-stage clinical trials in Parkinson disease, yet evidence of their role in oncology is limited. This review will compare the merits and challenges of these therapeutic approaches, identifying tumor indications and combinations that may be fruitful as they progress to the clinic.High concentrations of immunosuppressive adenosine have been reported in cancers, and adenosine is implicated in the growth of tumors. This brief review delineates the current treatment strategies and tumor subtypes that will benefit from targeting adenosinergic pathways, alone or in combination with contemporary approaches to cancer treatment.
Development of immunoglobulin λ-chain–positive B cells, but not editing of immunoglobulin κ-chain, depends on NF-κB signals
Authors: Emmanuel Derudder, Emily J Cadera, J Christoph Vahl, Jing Wang, Casey J Fox, Shan Zha, Geert van Loo, Manolis Pasparakis, Mark S Schlissel, Marc Schmidt-Supprian, Klaus Rajewsky
Journal: Nature Immunology (2009)
Performance Characteristics and Results of A Large–Scale Screening Program for Viral Hepatitis and Risk Factors Associated With Exposure to Viral Hepatitis B and C: Results of the National Hepatitis Screening Survey
Authors: S Kaur, L Rybicki, B R Bacon, J L Gollan, V K Rustgi, W D Carey
Journal: Hepatology (1996)

Chronic viral hepatitis frequently goes undetected until cirrhosis develops. Although the effect of interferon on the natural history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in asymptomatic persons is unknown, treatment may modify the course of the infection, producing cures in some. In September 1992, screening for HBV and HCV was offered in 40 centers throughout the United States. Demographic features, potential risk factors, and symptoms were studied. Blood samples were obtained for the determination of serum alanine aminotransferase levels and for markers of HBV and HCV infection. Thirteen thousand nine hundred ninety seven subjects were screened. The prevalence of infection with HBV or HCV was 24.8% (HBV 17.8%; HCV 7.0%; and both 2.8%). Hepatitis B and C disease was present in 0.7% and 4.4% of the population, respectively. Risk factors for HBV and HCV infection were similar in: blood transfusions, hemodialysis, IV drug use, and sex with an IV drug user. For HBV infection, sex with multiple partners, increasing age, and birth in South East Asia or Africa were additional risk factors. The cost to find a case of HCV infection is less than the costs for finding many other treatable diseases. Screening for HBV, though more costly, is reasonably efficient, and simultaneous screening for HBV and HCV provides greater efficiency. It is practical to consider screening for HBV and HCV in the United States, particularly if any risk factor is present. Improved treatment strategies will make screening even more cost effective.
Quantum Dots as Cellular Probes
Authors: A. Paul Alivisatos, Weiwei Gu, Carolyn Larabell
Journal: Annual Review of Biomedical Engineering (2005)

▪ Abstract Robust and bright light emitters, semiconductor nanocrystals [quantum dots (QDs)] have been adopted as a new class of fluorescent labels. Six years after the first experiments of their uses in biological applications, there have been dramatic improvements in understanding surface chemistry, biocompatibility, and targeting specificity. Many studies have shown the great potential of using quantum dots as new probes in vitro and in vivo. This review summarizes the recent advances of quantum dot usage at the cellular level, including immunolabeling, cell tracking, in situ hybridization, FRET, in vivo imaging, and other related technologies. Limitations and potential future uses of quantum dot probes are also discussed.
Colour M‐mode velocity propagation: a glance at intra‐ventricular pressure gradients and early diastolic ventricular performance
Authors: Bart W.L. De Boeck, Jae K. Oh, Pieter M. Vandervoort, Jan A. Vierendeels, Ronald P.L.M. van der Aa, Maarten‐Jan M. Cramer
Journal: European Journal of Heart Failure (2005)
Activation of WD Repeat and High-Mobility Group Box DNA Binding Protein 1 in Pulmonary and Esophageal Carcinogenesis
Authors: Nagato Sato, Junkichi Koinuma, Masahiro Fujita, Masao Hosokawa, Tomoo Ito, Eiju Tsuchiya, Satoshi Kondo, Yusuke Nakamura, Yataro Daigo
Journal: Clinical Cancer Research (2009)

We attempted to identify novel biomarkers and therapeutic targets for lung and esophageal cancers.We screened for genes that were overexpressed in a large proportion of lung and esophageal carcinomas using a cDNA microarray representing 27,648 genes or expressed sequence tags. A gene encoding WDHD1, a WD repeat and high-mobility group box DNA binding protein 1, was selected as a candidate. Tumor tissue microarray containing 267 archival non-small cell lung cancers and 283 esophageal squamous cell carcinomas (ESCC) was used to investigate the clinicopathologic significance of WDHD1 expression. The role of WDHD1 in cancer cell growth and/or survival was examined by small interfering RNA experiments and cell growth assays. The mechanism of WDHD1 activation through its phosphorylation in cancer cells was examined by immunoprecipitation and kinase assays.Positive WDHD1 immunostaining was associated with a poor prognosis for patients with non-small cell lung cancer (P = 0.0403) as well as ESCC (P = 0.0426). Multivariate analysis indicated it to be an independent prognostic factor for ESCC (P = 0.0104). Suppression of WDHD1 expression with small interfering RNAs effectively suppressed lung and esophageal cancer cell growth. In addition, induction of the exogenous expression of WDHD1 promoted the growth of mammalian cells. AKT1 kinase seemed to phosphorylate and stabilize the WDHD1 protein in cancer cells.WDHD1 expression is likely to play an important role in lung and esophageal carcinogenesis as a cell cycle regulator and a downstream molecule in the phosphoinositide 3-kinase/AKT pathway, and that WDHD1 is a candidate biomarker and a promising therapeutic target for cancer.
Predictors of luminal narrowing by neointima after angioplasty in atherosclerotic rabbits
Authors: S Gertz
Journal: Cardiovascular Research (1997)

The present study was designed to identify the predictors of cross-sectional area narrowing by neointima (%CSAN-N) after balloon angioplasty (BA) in the cholesterol fed rabbit model.Angiographic, histomorphometric, and immunohistochemical data were analyzed from 91 femoral arteries of New Zealand white rabbits. Focal atherosclerosis was induced by air desiccation of the endothelium followed by a 2% cholesterol diet for 28 days. The rabbits received heparin (150 U/kg) at the time of BA (2.5 mm; three, 60-second, 10-atm inflations). Arteries were perfusion-fixed and excised 7 (n = 16), 14 (n = 11), 21 (n = 9), or 28 (n = 20) days after BA. Non-angioplastied arteries were de-endothelialized (cholesterol-fed [n = 12] or normal diet [n = 8]), non-injured but cholesterol-fed (n = 7), or normal (n = 8).Univariate regression across all groups showed that the absolute area of the lumen by histomorphometry (LA) correlated significantly with the area bounded by the external elastic lamina (EEL) (vessel size), but no correlation was found with the absolute area of neointima or media, the percentage disruption of the internal elastic lamina (IEL), or the percentage of neointima and media occupied by foam cells. However, %CSAN-N correlated significantly with the area bounded by the EEL, significantly with the absolute neointimal area, and negatively with the absolute LA (p < 0.0001). Significant correlations were also found between %CSAN-N and the % IEL disrupted, the area of neointima and media occupied by RAM-11 + foam cells, and the loss of alpha-actin positivity in the media (p < 0.0001).These studies show that neointimal formation contributes significantly to luminal narrowing 1 month after angioplasty in this model, that the degree of vascular injury and the extent of foam cell accumulation in the neointima and media are significant independent predictors of neointimal formation, and that the area of the neointima, and the percent narrowing by neointima, are important predictors of remodeling itself (EEL area). These predictors were not identifiable when the analysis was focused on the determinants of absolute luminal area alone.
Neurotoxic Effects of Alcohol in Adolescence
Authors: Joanna Jacobus, Susan F. Tapert
Journal: Annual Review of Clinical Psychology (2012)

This review examines neuroimaging and neurocognitive findings on alcohol-related toxicity in adolescents. Teens who meet criteria for alcohol use disorders, as well as those who engage in subdiagnostic binge drinking behaviors, often show poorer neurocognitive performance, alterations in gray and white matter brain structure, and discrepant functional brain activation patterns when compared to nonusing and demographically matched controls. Abnormalities are also observed in teens with a family history of alcoholism, and such differences in neuromaturation may leave youths at increased risk for the development of an alcohol use disorder or increased substance use severity. More prospective investigations are needed, and future work should focus on disentangling preexisting differences from dose-dependent effects of alcohol on neurodevelopment. Intervention strategies that utilize neuroimaging findings (e.g., identified weaknesses in particular neural substrates and behavioral correlates) may be helpful in both prevention and intervention campaigns for teens both pre- and postinitiation of alcohol use.
A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs
Authors: E H Choy
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> In rheumatoid arthritis (RA), intramuscular (IM) pulsed depomedrone expedites an immediate response to disease modifying antirheumatic drugs (DMARDs). Although IM depomedrone is also widely used to treat disease flares in patients treated with DMARDs, its effect on radiological progression has not been assessed. <b>Objective:</b> To evaluate the benefits of 120 mg IM depomedrone versus placebo in patients with established RA whose disease was inadequately controlled by existing DMARDs. <b>Methods:</b> In a 2 year prospective randomised controlled trial patients were assessed using the ILAR/WHO core dataset, disease activity score (DAS28), <i>x</i> ray examination of hands and feet scored by Larsen's method, and bone densitometry. <b>Results:</b> 291 patients with RA were screened, 166 were eligible, and 91 consented and were randomised. Disease activity improved more rapidly in the steroid treated patients than with placebo, but after 6 months no difference remained. A small but significant reduction in erosive damage in the steroid group compared with placebo was also found. More adverse reactions occurred in the steroid treated group than in the placebo patients (55 <i>v</i> 42), especially those reactions traditionally related to steroids (16 <i>v</i> 2), including vertebral fracture, diabetes, and myocardial infarction. Hip bone density fell significantly in steroid treated but not placebo patients. <b>Conclusions:</b> IM depomedrone improved disease activity in the short term and produced a small reduction in bone erosion at the cost of a significant increase in adverse events. Despite the initial benefit of IM depomedrone, when patients respond suboptimally to a DMARD they should not be given long term additional steroids but should be treated with alternative or additional DMARDs.
Production of an inhibitor of rat mesangial cell growth by the glomerulus and its alteration in puromycin nephrosis.
Authors: G C Groggel, M L Hughes
Journal: Journal of the American Society of Nephrology (1993)

Mesangial cell proliferation is found in many forms of progressive renal disease. This proliferation may be due to dysregulation of mesangial cell growth. The studies presented here test the hypothesis that the normal glomerulus produces a regulator of mesangial cell growth. Conditioned media (CM) from primary glomerular cultures were able to inhibit rat mesangial cell growth in a dose- and time-dependent fashion, from 30.0 +/- 3.8 to 86.6 +/- 3.9% growth inhibition. The growth inhibitor in glomerular CM appears to have a molecular weight of less than 3,000. Glomerular CM caused significantly more growth inhibition than did 3T3 fibroblast CM, 77.9 +/- 2.8% growth inhibition by 10% glomerular CM versus 21.2 +/- 5.4% by 10% 3T3 CM (P < 0.001). The growth inhibition was completely reversible. Glomerular CM had no effect on the growth of 3T3 fibroblasts. Treatment of the glomerular CM with either trypsin or neutral protease had no effect on its growth inhibitory activity. Glomerular CM obtained from rats with puromycin aminonucleoside nephrosis caused significantly less growth inhibition than did control glomerular CM; at a concentration of 10% CM, control glomerular CM had 65.1 +/- 1.9% growth inhibition and puromycin had 45.4 +/- 2.1% (P < 0.001). Thus, the rat glomerulus produces a small, nonprotein inhibitor of rat mesangial cell growth and the activity of this inhibitor is reduced in puromycin nephrosis. Impairment of mesangial cell growth regulation may be important in the pathogenesis of progressive renal disease.
Self-antigen–presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs
Authors: Alberto Pugliese, Douglas Brown, David Garza, Djanira Murchison, Markus Zeller, Maria Redondo, Juan Diez, George S. Eisenbarth, Dhavalkumar D. Patel, Camillo Ricordi
Journal: Journal of Clinical Investigation (2001)

Recent reports indicate that genes with tissue-restricted expression, including those encoding the type 1 diabetes autoantigens insulin, glutamic acid decarboxylase (GAD), and the tyrosine-phosphatase-like protein IA-2 (or ICA512), are transcribed in the thymus. The reported modulation of diabetes susceptibility by genetically determined differences in thymic insulin levels and studies in transgenic mice provide correlative and functional evidence that thymic expression of peripheral proteins is crucial for immunological self-tolerance. However, there are no specific data about the existence, tissue distribution, phenotype, and function of those cells that express insulin and other self-antigens in the human thymus. We find that the human thymus harbors specialized cells synthesizing (pro)insulin, GAD, and IA-2, mainly localized in the medulla, and we demonstrate such cells also in peripheral lymphoid organs (spleen and lymph nodes). Phenotypic analysis qualifies these cells as antigen-presenting cells (APCs), including both dendritic cells and macrophages. These cells often appear surrounded by apoptotic lymphocytes, both in thymus and spleen, and may therefore be involved in the deletion of autoreactive lymphocytes. Our findings demonstrate the existence of, and define the tissue distribution and phenotype of, a novel subset of APCs expressing self-antigens in human lymphoid organs that appear to be involved in the regulation of self-tolerance throughout life.
Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study
Authors: H. Grasemann, C. Grasemann, F. Kurtz, G. Tietze-Schillings, U. Vester, F. Ratjen
Journal: European Respiratory Journal (2005)

Exhaled nitric oxide (eNO) is decreased in cystic fibrosis (CF). The effect of oral L -arginine, the precursor of enzymatic nitric oxide (NO) formation, on airway NO in patients with CF was studied. In a pilot study, oral L -arginine was given in a single dose of 200 mg·kg −1 body weight to eight healthy controls and eight CF patients. Subsequently, the same L -arginine dose was given to 10 patients with CF (five females) t.i.d. for 6 weeks in a randomised double-blind placebo-controlled crossover study. A single dose of oral L -arginine resulted in a 5.5-fold increase of L -arginine in plasma and a 1.3-fold increase of L -arginine in sputum after 2 h. Maximum eNO, within 3 h of L -arginine intake, increased significantly in both CF patients (5.4±2.1 ppb versus 8.3±3.5 ppb) and controls (18.0±8.1 ppb versus 26.4±12.3 ppb). Supplementation of L -arginine for 6 weeks resulted in a sustained increase in eNO compared to placebo (9.7±5.7 ppb versus 6.3±3.1 ppb). An effect of L -arginine supplementation on forced expiratory volume in one second was not observed. These data indicate that airway nitric oxide formation in cystic fibrosis patients can be augmented with oral L -arginine supplementation.
Octreotide treatment of idiopathic pulmonary fibrosis: a proof-of-concept study
Authors: B. Crestani, J. Chapron, B. Wallaert, E. Bergot, P. Delaval, D. Israel-Biet, J. Lacronique, I. Monnet, M. Reynaud-Gaubert, A. Tazi, R. Lebtahi, M-P. Debray, M. Brauner, M. Dehoux, Q. Dornic, M. Aubier, F. Mentré, X. Duval
Journal: European Respiratory Journal (2012)

<h3>Abstract</h3> This paper compares the contact-repulsion movement of mutant and wild-type macrophages using a novel interaction detection mechanism. The migrating macrophages are observed in <i>Drosophila</i> embryos. The study is carried out by a framework called macrosight, which analyses the movement and interaction of migrating macrophages. The framework incorporates a segmentation and tracking algorithm into analysing motion characteristics of cells after contact. In this particular study, the interactions between cells is characterised in the case of control embryos and Shot3 <i>mutants</i>, where the cells have been altered to suppress a specific protein, looking to understand what drives the movement. Statistical significance between control and mutant cells was found when comparing the direction of motion after contact in specific conditions. Such discoveries provide insights for future developments in combining biological experiments to computational analysis. Cell Segmentation, Cell Tracking, Macrophages, Cell Shape, Contact Analysis
Development of Autoantibody Signatures as Novel Diagnostic Biomarkers of Non–Small Cell Lung Cancer
Authors: Lingling Wu, Wenjun Chang, Jinfeng Zhao, Yongwei Yu, Xiaojie Tan, Tong Su, Lijun Zhao, Shengdong Huang, Shiyuan Liu, Guangwen Cao
Journal: Clinical Cancer Research (2010)

To select autoantibody signatures as noninvasive biomarkers of non-small cell lung cancer (NSCLC).A phage cDNA expression library was constructed with fresh samples from 30 lung cancer patients and biopanned using serum pools of 10 NSCLC patients and 10 healthy controls. A six-phage peptide detector was discovered by two-step immunoscreenings and was validated in an independent set of 90 NSCLC patients and 90 matched healthy controls, 30 NSCLC patients with chemotherapy, and 12 chronic obstructive pulmonary disease (COPD) patients. The expression of a peptide target was validated by using immunohistochemistry. Factors affecting NSCLC-related death were evaluated by Cox regression analysis.Six phage peptide clones showing higher seroreactivity than others in 30 NSCLC patients were selected for diagnostic validation. The six-phage peptide detector was able to discriminate between NSCLC patients and healthy controls with a sensitivity and specificity of >92%, and had similar validity for indicating NSCLC at early stage. The seroreactivity of the six phage peptides was significantly higher in the NSCLC patients than in those with chemotherapy and the COPD patients, respectively. Of the six phage peptides, one encoded a peptide showing 100% homology to olfactomedin 1. Expression of olfactomedin 1 protein was significantly higher in lung adenocarcinoma than in lung cancer of other histologic types and normal lung tissues. The autoantibody signature was not associated with the prognosis of the NSCLC patients.The six-phage peptide detector stands out as promising diagnostic biomarkers for NSCLC, unlikely for NSCLC relapse after chemotherapy. Olfactomedin 1 may be a novel target of lung adenocarcinoma.