tbuckley/cabot-search huggingface dataset:
Increased expression of MMP-2, MMP-9 (type IV collagenases/gelatinases), and MT1-MMP in canine X-linked Alport syndrome (XLAS)
Authors: Velidi H Rao, George E Lees, Clifford E Kashtan, Ryochi Nemori, Rakesh K Singh, Daniel T Meehan, Kathyrn Rodgers, Brian R Berridge, Gautam Bhattacharya, Dominic Cosgrove
Journal: Kidney International (2003)
Molecular Targeting and Treatment of EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibody L8A4
Authors: Weilian Yang, Rolf F. Barth, Gong Wu, Shinji Kawabata, Thomas J. Sferra, Achintya K. Bandyopadhyaya, Werner Tjarks, Amy K. Ferketich, Melvin L. Moeschberger, Peter J. Binns, Kent J. Riley, Jeffrey A. Coderre, Michael J. Ciesielski, Robert A. Fenstermaker, Carol J. Wikstrand
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The purpose of the present study was to evaluate a boronated EGFRvIII-specific monoclonal antibody, L8A4, for boron neutron capture therapy (BNCT) of the receptor-positive rat glioma, F98npEGFRvIII. Experimental Design: A heavily boronated polyamido amine (PAMAM) dendrimer (BD) was chemically linked to L8A4 by two heterobifunctional reagents, N-succinimidyl 3-(2-pyridyldithio)propionate and N-(k-maleimidoundecanoic acid)hydrazide. For in vivo studies, F98 wild-type receptor-negative or EGFRvIII human gene-transfected receptor-positive F98npEGFRvIII glioma cells were implanted i.c. into the brains of Fischer rats. Biodistribution studies were initiated 14 days later. Animals received [125I]BD-L8A4 by either convection enhanced delivery (CED) or direct i.t. injection and were euthanized 6, 12, 24, or 48 hours later. Results: At 6 hours, equivalent amounts of the bioconjugate were detected in receptor-positive and receptor-negative tumors, but by 24 hours the amounts retained by receptor-positive gliomas were 60.1% following CED and 43.7% following i.t. injection compared with 14.6% ID/g by receptor-negative tumors. Boron concentrations in normal brain, blood, liver, kidneys, and spleen all were at nondetectable levels (&amp;lt;0.5 μg/g) at the corresponding times. Based on these favorable biodistribution data, BNCT studies were initiated at the Massachusetts Institute of Technology Research Reactor-II. Rats received BD-L8A4 (∼40 μg 10B/∼750 μg protein) by CED either alone or in combination with i.v. boronophenylalanine (BPA; 500 mg/kg). BNCT was carried out 24 hours after administration of the bioconjugate and 2.5 hours after i.v. injection of BPA for those animals that received both agents. Rats that received BD-L8A4 by CED in combination with i.v. BPA had a mean ± SE survival time of 85.5 ± 15.5 days with 20% long-term survivors (&amp;gt;6 months) and those that received BD-L8A4 alone had a mean ± SE survival time of 70.4 ± 11.1 days with 10% long-term survivors compared with 40.1 ± 2.2 days for i.v. BPA and 30.3 ± 1.6 and 26.3 ± 1.1 days for irradiated and untreated controls, respectively. Conclusions: These data convincingly show the therapeutic efficacy of molecular targeting of EGFRvIII using either boronated monoclonal antibody L8A4 alone or in combination with BPA and should provide a platform for the future development of combinations of high and low molecular weight delivery agents for BNCT of brain tumors.
Imaging of amyloid β in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism
Authors: Christopher C Rowe, Uwe Ackerman, William Browne, Rachel Mulligan, Kerryn L Pike, Graeme O'Keefe, Henry Tochon-Danguy, Gordon Chan, Salvatore U Berlangieri, Gareth Jones, Kerryn L Dickinson-Rowe, Hank P Kung, Wei Zhang, Mei Ping Kung, Daniel Skovronsky, Thomas Dyrks, Gerhard Holl, Sabine Krause, Matthias Friebe, Lutz Lehman, Stefanie Lindemann, Ludger M Dinkelborg, Colin L Masters, Victor L Villemagne
Journal: The Lancet Neurology (2008)
Nucleotide Variation at the yellow Gene Region is not Reduced in Drosophila subobscura: A Study in Relation to Chromosomal Polymorphism
Authors: A Munté, M Aguadé, C Segarra
Journal: Molecular Biology and Evolution (2000)

In contrast to Drosophila melanogaster and Drosophila simulans, the yellow (y) gene region of Drosophila subobscura is not located in a region with a strong reduction in recombination. In addition, this gene maps very close to the breakpoints of different inversions that segregate as polymorphic in natural populations of D. subobscura. Therefore, levels of variation at the y gene region in this species relative to those found in D. melanogaster and D. simulans may be affected not only by the change in the recombinational environment, but also by the presence of inversion polymorphism. To further investigate these aspects, an approximately 5.4-kb region of the A (=X) chromosome including the y gene was sequenced in 25 lines of D. subobscura and in the closely related species Drosophila madeirensis and Drosophila guanche. The D. subobscura lines studied differed in their A-chromosomal arrangements, Ast, A2, and A1. Unlike in D. melanogaster and D. simulans, levels of variation at the y gene region of D. subobscura are not reduced relative to those found at other genomic regions in the same species (rp49, Acp70A, and Acph-1). This result supports the effect of the change in the recombinational environment of a particular gene on the level of neutral variation. In addition, nucleotide variation is affected by chromosomal polymorphism. A strong genetic differentiation is detected between the A1 arrangement and either Ast or A2, but not between Ast and A2. This result is consistent with the location of the y gene relative to the breakpoints of inversions A1 and A2. In addition, the pattern of nucleotide polymorphism in Ast+A2 and A1 seems to point out that variation at the y gene region within these chromosomal classes is in the phase transient to equilibrium. The estimated ages of these arrangements assuming a star genealogy indicate that their origin cannot predate the D. madeirensis split. Therefore, the present results are consistent with a chromosomal phylogeny where Am1, which is an arrangement present in D. madeirensis but absent in current populations of D. subobscura, would be the ancestral arrangement.
Cancer Genetics and the Cardiotoxicity of the Therapeutics
Authors: Hind Lal, Kyle L. Kolaja, Thomas Force
Journal: Journal of the American College of Cardiology (2013)

Cancer genomics has focused on the discovery of mutations and chromosomal structural rearrangements that either increase susceptibility to cancer or support the cancer phenotype. Protein kinases are the most frequently mutated genes in the cancer genome, making them attractive therapeutic targets for drug design. However, the use of some of the kinase inhibitors (KIs) has been associated with toxicities to the heart and vasculature, including acute coronary syndromes and heart failure. Herein we discuss the genetic basis of cancer, focusing on mutations in the kinase genome (kinome) that lead to tumorigenesis. This will allow an understanding of the real and potential power of modern cancer therapeutics. The underlying mechanisms that drive the cardiotoxicity of the KIs are also examined. The preclinical models for predicting cardiotoxicity, including induced pluripotent stem cells and zebrafish, are reviewed, with the hope of eventually being able to identify problematic agents before their use in patients. Finally, the use of biomarkers in the clinic is discussed, and newer strategies (i.e., metabolomics and enhanced imaging strategies) that may allow earlier and more accurate detection of cardiotoxicity are reviewed.
Tumor Necrosis Factor-α Upregulates Angiotensin II Type 1 Receptors on Cardiac Fibroblasts
Authors: Devorah Gurantz, Randy T. Cowling, Francisco J. Villarreal, Barry H. Greenberg
Journal: Circulation Research (1999)

Abstract —Angiotensin II (Ang II) plays an important role in post–myocardial infarction (MI) remodeling. Most Ang II effects related to remodeling involve activation of the type 1 receptor (AT 1 ). Although the AT 1 receptor is upregulated on cardiac fibroblasts post-MI, little is known about the mechanisms involved in the process. Consequently, we tested whether growth factors known to be present in the remodeling heart increased AT 1 mRNA levels. Using quantitative competitive reverse transcription–polymerase chain reaction, we found that norepinephrine, endothelin, atrial natriuretic peptide, and bradykinin had no significant effect on AT 1 mRNA levels. Ang II, transforming growth factor-β 1 , and basic fibroblast growth factor reduced AT 1 mRNA levels ( P &lt;0.02). Tumor necrosis factor-α (TNF-α), however, produced a marked increase in AT 1 mRNA. After 24 hours of TNF-α incubation, AT 1 mRNA increased by 5-fold above control levels ( P &lt;0.01). The EC 50 for the TNF-α effect was 4.6 ng/mL (0.2 nmol/L). Interleukin (IL)-1β caused a 2.4-fold increase, whereas IL-2 and IL-6 had no significant effect. Studies of TNF-α enhancement of AT 1 mRNA levels demonstrate that the increase was not due to a change in transcript stability. TNF-α treatment for 48 hours also resulted in a 3-fold increase in AT 1 surface receptor and a 2-fold increase in Ang II–induced production of inositol phosphates. The present findings provide evidence for TNF-α regulation of AT 1 receptor density on cardiac fibroblasts. Because TNF-α concentration and AT 1 receptor density increase in the myocardium after MI, these results raise the possibility that TNF-α modulates post-MI remodeling by enhancing Ang II effects on cardiac fibroblasts.
New MRC guidance on evaluating complex interventions
Authors: R. Anderson
Journal: BMJ (2008)

Neuroendocrine tumours (NETs) of the urinary tract are rare, and the urinary bladder is the the most common primary site. Primary ureteric NET is rarer with under 80 cases reported in the literature thus far. Most of these tumours are of the high-grade small cell neuroendocrine carcinoma subtype, which has a worse prognosis. Neoadjuvant chemotherapy has a proven role in the management of NET of the bladder as it downstages the tumour, which may add to significant recurrence-free survival and overall survival. We report the successful management of a patient with locally advanced small cell neuroendocrine carcinoma of the ureter, who had a pathological complete response after neoadjuvant chemotherapy with etoposide and cisplatin. He subsequently received adjuvant chemotherapy followed by radiation and is recurrence-free at a follow-up of 1 year.
Molecular imaging using contrast-enhanced ultrasound: evaluation of angiogenesis and cell therapy
Authors: H. Leong-Poi
Journal: Cardiovascular Research (2009)

The field of regenerative medicine and its applications for cardiovascular diseases continues to grow rapidly, fuelled by the increasing numbers of symptomatic patients who are not candidates for conventional revascularization procedures and remain refractory to maximal medical therapy. Therapeutic angiogenesis, initially in the form of the administration of growth factor protein or gene therapy and, more recently, in the form of adult progenitor cell therapy, has emerged as a promising new method of treatment for patients with ischaemic heart disease and peripheral arterial disease. There is a growing interest in non-invasive imaging techniques to evaluate the response to angiogenic gene-and cell-based therapies. Contrast-enhanced ultrasound (CEU) techniques using site-specific microbubbles have recently been developed for the molecular imaging of the vascular phenotype that characterizes angiogenesis. These methods have now been modified to allow the imaging of progenitor cell engraftment into neovessels. These molecular imaging techniques using contrast ultrasound and targeted microbubbles have the potential to further characterize the angiogenic response, aid in the optimization of gene- and cell-based strategies of therapeutic neovascularization, and ultimately serve to monitor the therapeutic effects in patients enrolled in clinical trials of regenerative therapies. This review will focus specifically on CEU molecular imaging techniques for the evaluation of angiogenesis and cell therapies in cardiovascular diseases, including: (i) an overview of the techniques and results of pre-clinical studies; (ii) a comparison of CEU molecular imaging techniques with other available molecular imaging modalities; and (iii) a discussion of the future role of CEU molecular imaging in the field of regenerative medicine.
CELLULAR IMMUNOABSORBENTS IN TRANSPLANTATION IMMUNITY
Authors: Gideon Berke, Raphael H. Levey
Journal: The Journal of Experimental Medicine (1972)

Mouse lymphoid cells, sensitized against tumor allografts, can be deprived of the immunoreactive cells by in vitro absorption with specific fibroblast monolayers. Populations of lymphocytes so depleted are less effective in retarding tumor growth in vivo and in lysing tumor cells in vitro. Moreover, the adsorbed immunoreactive cells can be recovered specifically and are subsequently efficient in inhibiting tumor growth in vivo and in killing tumor cells in vitro. Further evidence is presented for the suggestion that the destruction of target cells in vitro by sensitized lymphoid cells is truly representative of the mode of destruction of grafted cells in vivo.
Response to Letter Regarding Article, “Paclitaxel-Coated Balloon Catheter Versus Paclitaxel-Coated Stent for the Treatment of Coronary In-Stent Restenosis”
Authors: Bruno Scheller, Bodo Cremers, Martin Unverdorben, Ralf Degenhardt, Christian Vallbracht, Hubertus Heuer, Christian Hengstenberg, Christian Maikowski, Gerald S. Werner, Diethmar Antoni, Franz X. Kleber, Wolfgang Bocksch, Matthias Leschke, Hanns Ackermann, Michael Boxberger, Ulrich Speck
Journal: Circulation (2010)
Relation between HIV-1 syncytium inhibition antibodies and clinical outcome in children
Authors: T.J. Brenner, K.E. Dahl, G. Miller, W.A. Andiman, W.A. Andiman, B. Olson, G. Miller, W.A. Andiman, G. Miller
Journal: The Lancet (1991)

Syncytium formation, a feature of HIV-1-induced cytopathology, allows the virus to propagate through cell-to-cell spread. An assay has been developed to measure antibodies (syncytium inhibition, SI) that inhibit this process. Two cell lines were used: the indicator cells, which are not HIV-1 infected, bear CD4 receptors on their surface; the fusogenic HIV-1 infected cells, which do not release virus but are responsible for initiating syncytium formation, are free of CD4 receptors. Co-cultivation of about 105 of each of these cells induces the emergence of 70-100 multinucleated giant cells within 48 h. Sera from 34 children born to HIV-1-infected mothers were tested by western blot (WB) and SI assay. SI antibodies were detected in the blood of 15 (65%) of 23 WB-positive children and in none of 11 WB-negative children. There were striking differences in prevalence and titre of SI antibodies in children with lymphocytic interstitial pneumonitis (LIP) compared with those with opportunistic infections (01). All 8 children with LIP had SI antibodies ranging in titre from 40 to > 320. By contrast, only 2 of 7 with 01 had SI antibodies, in both of whom the SI titre was 20 (p<0·05). No sera from children who had seroreverted contained SI antibodies. The findings point to the need to identify the specific HIV-I peptides or epitopes responsible for syncytium formation since SI antibodies correlate with clinical outcome in children.
Identification of a potential physiological precursor of aberrant cells in refractory coeliac disease type II
Authors: Frederike Schmitz, Jennifer M L Tjon, Yuching Lai, Allan Thompson, Yvonne Kooy-Winkelaar, Richard J L F Lemmers, Hein W Verspaget, M Luisa Mearin, Frank J Staal, Marco W Schreurs, Tom Cupedo, Anton W Langerak, Chris J Mulder, Jeroen van Bergen, Frits Koning
Journal: Gut (2012)

<h3>Objective</h3> Refractory coeliac disease type II (RCDII) is a severe complication of coeliac disease (CD) characterised by aberrant intraepithelial lymphocytes (IELs) of unknown origin that display an atypical CD3<sup>−</sup>CD7<sup>+</sup>icCD3<sup>+</sup> phenotype. In approximately 40% of patients with RCDII these lymphocytes develop into an invasive lymphoma. In the current study we aimed to identify the physiological counterpart of these cells. <h3>Design</h3> RCDII cell lines were compared with T-cell receptor positive (TCR<sup>+</sup>) IEL (T-IEL) lines by microarray analysis, real-time quantitative PCR and flow cytometry. This information was used to identify cells with an RCDII-associated phenotype in duodenal biopsies from non-refractory individuals by multicolour flow cytometry. <h3>Results</h3> RCDII lines were transcriptionally distinct from T-IEL lines and expressed higher levels of multiple natural killer (NK) cell receptors. In addition to the CD3<sup>−</sup>CD7<sup>+</sup>icCD3<sup>+</sup> phenotype, the RCDII lines were distinguishable from other lymphocyte subsets by the absence of CD56, CD127 and CD34. Cells matching this surface lineage-negative (Lin<sup>−</sup>) CD7<sup>+</sup>CD127<sup>−</sup>CD34<sup>−</sup> phenotype expressed a functional interleukin-15 (IL-15) receptor and constituted a significant proportion of IELs in duodenal specimens of patients without CD, particularly children, and were also found in the thymus. In patients without CD, the Lin<sup>−</sup>CD7<sup>+</sup>CD127<sup>−</sup>CD34<sup>−</sup> subset was one of four subsets within the CD3<sup>−</sup>CD7<sup>+</sup>icCD3<sup>+</sup> population that could be distinguished on the basis of differential expression of CD56 and/or CD127. <h3>Conclusion</h3> Our studies indicate that the CD3<sup>−</sup>CD7<sup>+</sup>icCD3<sup>+</sup> population is heterogeneous and reveal the existence of a Lin<sup>−</sup> subset that is distinct from T, B, NK and lymphoid tissue inducer cells. We speculate that this IL-15 responsive population represents the physiological counterpart of aberrant cells expanded in RCDII and transformed in RCDII-associated lymphoma.
High prevalence of psoriatic arthritis in patients with severe psoriasis with suboptimal performance of screening questionnaires
Authors: Muhammad Haroon, Brian Kirby, Oliver FitzGerald
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> The objectives of this study were to: (1) assess the prevalence of psoriatic arthritis (PsA) among Psoriasis (Ps) patients attending dermatology clinics; (2) identify clinical predictors of the development of PsA; and (3) compare the performance of three PsA screening questionnaires: Psoriatic Arthritis Screening and Evaluation (PASE), Psoriasis Epidemiology Screening Tool (PEST) and Toronto Psoriatic Arthritis Screening (ToPAS). <h3>Methods</h3> Patients were divided into two groups: Group-1, consecutive psoriasis patients attending dermatology clinics with no known diagnosis of inflammatory arthritis and Group-2, consecutive patients attending rheumatology clinics with a confirmed diagnosis of PsA. In Group-1, patients completed the screening questionnaires, followed by a full rheumatological evaluation whether or not they reported musculoskeletal symptoms. <h3>Results</h3> 200 patients were recruited with 100 in each group. In all, 84% of patients in dermatology group were using systemic therapy for their skin disease, and 99% of patients in rheumatology group were on systemic immunosuppressives. In Group-1, 29% of patients were diagnosed with PsA after rheumatological evaluation. On univariate and multivariate analyses, there was a significant positive association between Psoriasis Area and Severity Index and a new diagnosis of PsA (p=0.046). Different patterns of joint involvement were noted in patients with newly diagnosed PsA versus patients with established PsA with fewer polyarticular disease presentations (p=0.0001). In Group-1, the PEST, PASE and ToPAS assessments had sensitivities of 27.5%, 24% and 41%, and specificities of 98%, 94% and 90%, respectively. In Group-2, the sensitivities were 86%, 62% and 83%, respectively. <h3>Conclusions</h3> 29% of Ps patients attending dermatology clinics had undiagnosed PsA. Psoriasis severity was associated with a new diagnosis of PsA. Poor sensitivities for the screening questionnaires were noted due to inadequate detection of patterns of arthritis other than polyarticular disease.
Persistent Right Umbilical Vein as a Result of Vitamin Deficiency During Gestation
Authors: I. W. MONIE, M. M. NELSON, H. M. EVANS
Journal: Circulation Research (1957)

Of the two umbilical veins formed in young rat embryos, the right regresses early while the left persists until birth. In a number of rat fetuses from mothers subjected to a transitory deficiency of pteroylglutamic ("folic") acid during pregnancy, this pattern was reversed and the right, instead of the left, umbilical vein persisted until birth. In such cases, the ductus venosus was always absent. No record of persistent right umbilical vein has been found in the literature.
First Nationwide Study of the Prevalence of the Metabolic Syndrome and Optimal Cutoff Points of Waist Circumference in the Middle East
Authors: Alireza Delavari, Mohammad Hossein Forouzanfar, Siamak Alikhani, Afsaneh Sharifian, Roya Kelishadi
Journal: Diabetes Care (2009)

OBJECTIVE The purpose of this study was to provide the first national estimate on the prevalence of the metabolic syndrome and its components and the first ethnic-specific cutoff point for waist circumference in the Eastern Mediterranean Region. RESEARCH DESIGN AND METHODS This national survey was conducted in 2007 on 3,024 Iranians aged 25–64 years living in urban and rural areas of all 30 provinces in Iran. The metabolic syndrome was defined by different criteria, namely the definition of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), the International Diabetes Federation (IDF) criteria, and the modified definition of the NCEP/ATP III (ATP III/American Heart Association [AHA]/National Heart, Lung, and Blood Institute [NHLBI]). RESULTS The age-standardized prevalence of the metabolic syndrome was about 34.7% (95% CI 33.1–36.2) based on the ATP III criteria, 37.4% (35.9–39.0%) based on the IDF definition, and 41.6% (40.1–43.2%) based on the ATP III/AHA/NHLBI criteria. By all definitions, the prevalence of the metabolic syndrome was higher in women, in urban areas, and in the 55- to 64-year age-group compared with the prevalence in men, in rural areas, and in other age-groups, respectively. The metabolic syndrome was estimated to affect &amp;gt;11 million Iranians. The optimal cutoff point of waist circumference for predicting at least two other components of the metabolic syndrome as defined by the IDF was 89 cm for men and 91 cm for women. CONCLUSIONS The high prevalence of the metabolic syndrome with its considerable burden on the middle-aged population mandates the implementation of national policies for its prevention, notably by tackling obesity. The waist circumference cutoff points obtained can be used in the region.