tbuckley/cabot-search huggingface dataset:
Matrix Metalloproteinases
Authors: Francis G. Spinale
Journal: Circulation Research (2002)

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes responsible for myocardial extracellular protein degradation. Several MMP species identified within the human myocardium may be dysregulated in congestive heart failure (CHF). For example, MMPs that are expressed at very low levels in normal myocardium, such as collagenase-3 (MMP-13) and the membrane-type-1 MMPs, are substantially upregulated in CHF. However, MMP species are not uniformly increased in patients with end-stage CHF, suggesting that a specific portfolio of MMPs are expressed in the failing myocardium. With the use of animal models of CHF, a mechanistic relationship has been demonstrated with respect to myocardial MMP expression and the left ventricular (LV) remodeling process. The tissue inhibitors of the MMPs (TIMPs) are locally synthesized proteins that bind to active MMPs and thereby regulate net proteolytic activity. However, there does not appear to be a concomitant increase in myocardial TIMPs during the LV remodeling process and progression to CHF. This disparity between MMP and TIMP levels favors a persistent MMP activation state within the myocardium and likely contributes to the LV remodeling process in the setting of developing CHF. The elucidation of upstream signaling mechanisms that contribute to the selective induction of MMP species within the myocardium as well as strategies to normalize the balance between MMPs and TIMPs may yield some therapeutic strategies by which to control myocardial extracellular remodeling and thereby slow the progression of the CHF process.
Standards for Measures Used for Public Reporting of Efficiency in Health Care
Authors: Harlan M. Krumholz, Patricia S. Keenan, John E. Brush, Vincent J. Bufalino, Michael E. Chernew, Andrew J. Epstein, Paul A. Heidenreich, Vivian Ho, Frederick A. Masoudi, David B. Matchar, Sharon-Lise T. Normand, John S. Rumsfeld, Jeremiah D. Schuur, Sidney C. Smith, John A. Spertus, Mary Norine Walsh
Journal: Journal of the American College of Cardiology (2008)
Activated CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis
Authors: H Kelchtermans, L Geboes, T Mitera, D Huskens, G Leclercq, P Matthys
Journal: Annals of the Rheumatic Diseases (2008)

Patients with rheumatoid arthritis (RA) have defective CD4(+)CD25(+) regulatory T (T(reg)) cells and increased osteoclastogenesis. A similar situation has been described in collagen-induced arthritis (CIA). In this study, it was investigated whether a single transfer of polyclonally activated T(reg) cells inhibits CIA and osteoclastogenesis.Purified T(reg) cells were expanded in vitro with anti-CD3 and anti-CD28 antibody-coated beads and injected into DBA/1 mice. Mice were immunised with collagen type II (CII) in complete Freund adjuvant (CFA) and scores of arthritis were recorded. In vitro osteoclastogenesis assays were performed on splenocytes by stimulation with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)kappaB ligand (RANKL). Levels of anti-CII antibody and cytokines were determined in the supernatant using ELISA and Bio-Plex protein array system.It was found that 10(6) activated T(reg) cells significantly counteracted the development of CIA, which was accompanied by decreased serum levels of TNFalpha and IL6, but not by inhibition of autoimmune antibody responses. The differentiation of osteoclasts in splenocyte cultures was significantly reduced in the presence of prestimulated T(reg) cells. Expression of cytokines that are described to inhibit osteoclastogenesis, including granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (IFN)gamma, interleukin (IL)5 and IL10, were dramatically increased upon addition of T(reg) cells. Furthermore, splenocytes from mice that had been treated with T(reg) cells displayed an impaired capacity to develop into mature osteoclasts, suggesting that T(reg) cells abrogated osteoclastogenesis in vivo.Activated CD4(+)CD25(+) T(reg) cells improve clinical symptoms of CIA, regulate cytokine production and inhibit osteoclastogenesis in vitro and in vivo.
Role of Leptin Deficiency in Early Acute Renal Failure during Endotoxemia in ob/ob Mice
Authors: Wei Wang, Brian Poole, Amit Mitra, Sandor Falk, Giamila Fantuzzi, Scott Lucia, Robert Schrier
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. It is known that, among human patients with sepsis, acute renal failure (ARF) dramatically increases mortality rates to 50 to 80%. However, the pathogenesis of septic ARF is not fully understood. An increase in endotoxin-induced mortality rates for leptin-deficient ob/ob mice was recently demonstrated. In comparison with ob/ob mice, db/db mice, which are deficient in the long isoforms of leptin receptors (Ob/Rb), demonstrate lower mortality rates after exposure to the endotoxin LPS. In db/db mice, mRNA for the short isoforms of leptin receptors is constitutively expressed in the kidney, lung, liver, and macrophages. It is known that plasma leptin levels increase in rodents after exposure to LPS, and this was demonstrated for db/db mice. Because ob/ob and db/db mice are both obese, factors other than obesity must be involved in the increased mortality rates for ob/ob mice. In this study, the hypothesis that the short forms of leptin receptors might offer protection against endotoxin-induced lethality at least in part by providing protection against ARF was examined. Serum leptin levels were significantly increased with LPS treatment in wild-type and db/db mice but not ob/ob mice. GFR decreased significantly 16 h after the homozygous ob/ob mice received intraperitoneal injections of 0.3 mg/kg LPS (0.37 ± 0.04 ml/min per g kidney versus 0.83 ± 0.06 ml/min per g kidney, n = 6, P < 0.01); the mean arterial pressure (MAP) remained unchanged. For ob/ob littermates (+/?ob), there was no significant change in either MAP or GFR when the mice were challenged with the same time interval (16 h) and dose of LPS. In contrast to ob/ob mice, there was no significant change in GFR or MAP when homozygous db/db mice or their littermates received injections of an even higher dose of LPS (0.4 mg/kg). Mouse recombinant leptin had no effect on GFR when ob/ob mice received 0.3 mg/kg LPS injections. However, renal function (serum creatinine levels, 0.4 ± 0.1 mg/dl versus 0.9 ± 0.1 mg/dl, P < 0.01) and MAP (68 ± 4 mmHg versus 51 ± 2 mmHg, n = 6, P < 0.01) were significantly improved with leptin replacement when the ob/ob mice developed hypotensive ARF with a higher dose of LPS (0.5 mg/kg). In summary, the previously reported increased susceptibility to LPS of ob/ob mice, compared with db/db mice, may be attributable at least in part to increased susceptibility to ARF.
Should Randomized Clinical Trials Be Required for Proton Radiotherapy? An Alternative View
Authors: Eli Glatstein, John Glick, Larry Kaiser, Stephen M. Hahn
Journal: Journal of Clinical Oncology (2008)

Eli Glatstein, Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA John Glick, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA Larry Kaiser, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA Stephen M. Hahn, Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA
Numerical representation in the parietal lobes: Abstract or not abstract?
Authors: Roi Cohen Kadosh, Vincent Walsh
Journal: Behavioral and Brain Sciences (2009)

Abstract The study of neuronal specialisation in different cognitive and perceptual domains is important for our understanding of the human brain, its typical and atypical development, and the evolutionary precursors of cognition. Central to this understanding is the issue of numerical representation, and the question of whether numbers are represented in an abstract fashion. Here we discuss and challenge the claim that numerical representation is abstract. We discuss the principles of cortical organisation with special reference to number and also discuss methodological and theoretical limitations that apply to numerical cognition and also to the field of cognitive neuroscience in general. We argue that numerical representation is primarily non-abstract and is supported by different neuronal populations residing in the parietal cortex.
Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure
Authors: Madhuri S Salker, Mark Christian, Jennifer H Steel, Jaya Nautiyal, Stuart Lavery, Geoffrey Trew, Zoe Webster, Marwa Al-Sabbagh, Goverdhan Puchchakayala, Michael Föller, Christian Landles, Andrew M Sharkey, Siobhan Quenby, John D Aplin, Lesley Regan, Florian Lang, Jan J Brosens
Journal: Nature Medicine (2011)
<i>In vivo</i>thickness measurement of basal cell carcinoma and actinic keratosis with optical coherence tomography and 20-MHz ultrasound
Authors: M. Mogensen, B.M. Nürnberg, J.L. Forman, J.B. Thomsen, L. Thrane, G.B.E. Jemec
Journal: British Journal of Dermatology (2009)

Accurate assessment of tumour size is important when planning treatment of nonmelanoma skin cancer (NMSC). Imaging with optical coherence tomography (OCT) has the potential to diagnose and measure depth of NMSC.To compare accuracy of mean tumour thickness measurement in NMSC tumours < 2 mm of depth using OCT and 20-MHz high-frequency ultrasound (HFUS). In addition, OCT morphology of NMSC was studied in OCT images and the influence of histological and colorimetric values on the quality and penetration depth in OCT images was estimated.In total, 93 patients were scanned and 34 lesions [23 basal cell carcinoma (BCC) and 11 actinic keratosis (AK) lesions] < 2 mm thick and easily identified in OCT images were studied. OCT and HFUS were compared with biopsies. The influence of skin pigmentation and infiltration analgesia on OCT image quality was studied. Skin colour was measured with a colorimeter.OCT presented narrower limits of agreement than HFUS. Both methods overestimated thickness but OCT was significantly less biased (0.392 mm vs. 0.713 mm). No relation between OCT penetration depth and skin colour was found.OCT appears more precise and less biased than HFUS for thickness measurement in AK and BCC lesions < 2 mm, but both OCT and especially HFUS tended to overestimate tumour thickness.
A breakthrough in the functional evaluation of the inspiratory muscle pump
Authors: T.L. Clanton
Journal: European Respiratory Journal (2002)

In this issue, Hart et al. 1 describe a new respiratory muscle endurance test that could greatly impact the understanding of clinical respiratory muscle biology in a variety of patient groups. In a post-genomic era, in which breakthroughs in both the understanding of diseases at a molecular level and the treatments based on designer molecules occur daily, why should this warrant news?

Look to the cardiologists. Cardiologists do not hesitate to consider developing aggressive treatment options (as ambitious as gene therapy or stem cell implantation) to combat the influence of hypertension or cardiac failure. These approaches are considered even though ventricular muscle disease does not represent the underlying cause of the disorder. Pulmonologists have traditionally been much more conservative. Their research and treatment modalities have focused exclusively on the underlying pathology of the lung, even …
Parasitic arthritis induced by Strongyloides stercoralis.
Authors: T Akoglu, I Tuncer, E Erken, A Gurcay, F L Ozer, K Ozcan
Journal: Annals of the Rheumatic Diseases (1984)

<h3>Abstract</h3> To explain the social difficulties in autism, a large amount of research has been conducted on the neural correlates of social perception. However, this research has mostly used basic social stimuli (e.g. eyes, faces, hands, single agent), not resembling the complexity of what we encounter in our daily social lives, and as such, the situations people with autism experience difficulties in. A more complex stimulus that we do come across often and is also highly relevant for social functioning is that of third-party social interactions. Here, we investigated if individuals with and without autism process third-party social interactions differently. More specifically, we measured neural responses to social scenes depicting either social interaction or not with an electroencephalogram (EEG) frequency tagging task and compared these responses between adults with and without autism (<i>N</i> = 61). The results revealed an enhanced response to social scenes with interaction, replicating previous findings in a neurotypical sample (Oomen et al., 2022). Crucially, this effect was found in both groups with no difference between them. This suggest that social interaction recognition is not anomalous in adults with autism and cannot explain the social difficulties adults with autism experience. <h3>Lay abstract</h3> People with autism have social difficulties and are thought to experience the world differently. To better understand these differences, research has studied how the brain of people with and without autism processes social stimuli. However, this research has mostly used basic social stimuli (e.g. eyes, faces, hands, and single agents). Such stimuli do not resemble the complexity of daily life, where we typically do not come across isolated body parts, but instead have to make sense of complex social scenes with multiple people. To do so, it is imperative that we are able to recognize social interaction. Hence, if social interaction processing is anomalous, this could have pervasive consequences for social functioning more generally. Here, we used brain imaging to test if adults with autism process social interaction scenes differently than adults without autism. In line with previous findings from a neurotypical sample (Oomen et al. (2022), we found that social scenes depicting interaction elicited stronger brain responses than social scenes not depicting interaction. Crucially, this effect was found in both groups with no difference between them. These findings suggest that the fundamental process of social interaction recognition is not anomalous in adults with autism.
REDUCTION OF ARTERIAL BLOOD PRESSURE OF HYPERTENSIVE PATIENTS AND ANIMALS WITH EXTRACTS OF KIDNEYS
Authors: Irvine H. Page, O. M. Helmer, K. G. Kohlstaedt, P. J. Fouts, G. F. Kempf
Journal: The Journal of Experimental Medicine (1941)

1. Extracts of kidneys have been prepared containing a substance which lowers arterial blood pressure for prolonged periods in patients with essential and malignant hypertension, and in hypertensive dogs and rats. 2. Several different chemical procedures are proposed for the preparation of the extract. The best one has not been decided upon. 3. The quantity of original fresh whole kidney required to yield enough extract to lower blood pressure from hypertensive levels (200 mm. Hg mean pressure) to normal levels is roughly 600 to 900 gm. in dogs within 4 to 8 days. In hypertensive patients the yield from 700 to 1000 gm. daily for several weeks may be necessary. 4. Lowering of the blood pressure too rapidly in animals results in a shock syndrome which may be fatal. If overdosage is avoided, no appreciable rise in blood urea nitrogen occurs, nor do other signs of toxicity appear. 5. Lowering of blood pressure to nearly normal levels has been accomplished in 60 hypertensive dogs, and in some of these it has been allowed to rise and was again reduced as many as five times. Similar results have been obtained with hypertensive rats. 6. Six patients with essential hypertension have been treated resulting in prolonged reduction of blood pressure. Clinically the patients appear improved. 7. Five patients with malignant hypertension have been treated, with reduction of the blood pressure in all instances. One patient was treated despite urea clearance of 5 per cent of normal. His blood pressure was sharply reduced, but death in uremia occurred. The second patient also exhibited sharp reduction of pressure and died after treatment was discontinued. The other three are much improved after treatment, as indicated by increase in vision and mental activity, loss of dyspnea, improvement in the electrocardiogram, etc. 8. The length of time the blood pressure remains lowered varies greatly in both animals and man. The trend is usually upwards after discontinuing treatment for 4 to 6 days. 9. Increasing experience with this treatment suggests that it is of value in the management of hypertension, but it is yet in the experimental stage.
Modulation of glomerular arteriolar tone by nitric oxide synthase inhibitors.
Authors: R M Edwards, W Trizna
Journal: Journal of the American Society of Nephrology (1993)

The inhibition of nitric oxide production has been shown to reduce RBF. The effects of the nitric oxide synthase inhibitors, N omega-nitro-L-arginine and NG-monomethyl-L-arginine, on afferent and efferent arterioles isolated from rabbit kidneys were examined. Under basal conditions, N omega-nitro-L-arginine (10(-7) to 10(-3) M) had no effect on efferent arteriole lumen diameter but caused a 40% decrease in the lumen diameter of afferent arterioles. In afferent and efferent arterioles precontracted with norepinephrine, N omega-nitro-L-arginine and NG-monomethyl-L-arginine (3 x 10(-4) M) markedly attenuated the vasorelaxant effects of the endothelium-dependent vasodilator acetylcholine. In both arterioles, the inhibitory effect of N omega-nitro-L-arginine on acetylcholine-induced relaxation could be reversed by L- but not D-arginine (10(-3) M). However, N omega-nitro-L-arginine had no effect on the relaxation produced by the endothelium-independent vasodilators prostaglandin E2 (afferent) and dopamine (efferent). These observations demonstrate that under the in vitro conditions used in this study, afferent arterioles but not efferent arterioles synthesize and release nitric oxide in the basal state. However, both arterioles release nitric oxide in response to an endothelium-dependent vasodilator. The results of this study provide further evidence for an important role of nitric oxide in the regulation of renal hemodynamics.
Immunogenicity of Constitutively Active V599EBRaf
Authors: Mads Hald Andersen, Joachim Fensterle, Selma Ugurel, Sine Reker, Roland Houben, Per Guldberg, Thomas G. Berger, Dirk Schadendorf, Uwe Trefzer, Eva-B. Bröcker, Per thor Straten, Ulf R. Rapp, Jürgen C. Becker
Journal: Cancer Research (2004)

Abstract Activating BRAF somatic missense mutations within the kinase domain are present in 60–66% of melanomas. The vast majority of these represent a single substitution of glutamate for valine (V599E). Here, we demonstrate spontaneous HLA-B*2705-restricted cytotoxic T-cell responses against an epitope derived from V599EBRaf. These T-cell responses were mutation specific as the corresponding epitope derived from wild-type BRaf was not recognized. The loss of the V599EBRAF genotype during progression from primary to metastatic melanoma in patients with V599EBRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.
Focal Adhesion Kinase Targeting Using <i>In vivo</i> Short Interfering RNA Delivery in Neutral Liposomes for Ovarian Carcinoma Therapy
Authors: Jyotsnabaran Halder, Aparna A. Kamat, Charles N. Landen, Liz Y. Han, Susan K. Lutgendorf, Yvonne G. Lin, William M. Merritt, Nicholas B. Jennings, Arturo Chavez-Reyes, Robert L. Coleman, David M. Gershenson, Rosemarie Schmandt, Steven W. Cole, Gabriel Lopez-Berestein, Anil K. Sood
Journal: Clinical Cancer Research (2006)

Focal adhesion kinase (FAK) plays a critical role in ovarian cancer cell survival and in various steps in the metastatic cascade. Based on encouraging in vitro results with FAK silencing, we examined the in vivo therapeutic potential of this approach using short interfering RNA (siRNA) in the neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC).Therapy experiments of FAK siRNA with or without docetaxel were done using human ovarian cancer cell lines SKOV3ip1, HeyA8, and HeyA8MDR in nude mice. Additional experiments with a cisplatin-resistant cell line (A2780-CP20) were also done. Assessments of angiogenesis (CD31), cell proliferation (proliferating cell nuclear antigen), and apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) were done using immunohistochemical analysis.A single dose of FAK siRNA-DOPC was highly effective in reducing in vivo FAK expression for up to 4 days as assayed by Western blot and immunohistochemical analysis. Therapy experiments were started 1 week after injection of the ovarian cancer cells. Treatment with FAK siRNA-DOPC (150 mug/kg twice weekly) reduced mean tumor weight by 44% to 72% in the three cell lines compared with the control group (Ps < 0.05 for HeyA8, A2780-CP20, and SKOV3ip1). When FAK siRNA-DOPC was combined with docetaxel, there was even greater reduction in mean tumor weight in all models (all Ps < 0.05). Similar results were observed in combination with cisplatin. Treatment with FAK siRNA-DOPC plus docetaxel resulted in decreased microvessel density, decreased expression of vascular endothelial growth factor and matrix metalloproteinase-9, and increased apoptosis of tumor-associated endothelial cells and tumor cells.Taken together, these findings suggest that FAK siRNA-DOPC plus docetaxel or platinum might be a novel therapeutic approach against ovarian cancer.
Favorable Prognostic Impact of <i>NPM1</i> Mutations in Older Patients With Cytogenetically Normal De Novo Acute Myeloid Leukemia and Associated Gene- and MicroRNA-Expression Signatures: A Cancer and Leukemia Group B Study
Authors: Heiko Becker, Guido Marcucci, Kati Maharry, Michael D. Radmacher, Krzysztof Mrózek, Dean Margeson, Susan P. Whitman, Yue-Zhong Wu, Sebastian Schwind, Peter Paschka, Bayard L. Powell, Thomas H. Carter, Jonathan E. Kolitz, Meir Wetzler, Andrew J. Carroll, Maria R. Baer, Michael A. Caligiuri, Richard A. Larson, Clara D. Bloomfield
Journal: Journal of Clinical Oncology (2009)

To analyze the prognostic significance of NPM1 mutations, and the associated gene- and microRNA-expression signatures in older patients with de novo, cytogenetically normal acute myeloid leukemia (CN-AML) treated with intensive chemotherapy.One hundred forty-eight adults age >or= 60 years with de novo CN-AML, enrolled onto Cancer and Leukemia Group B protocols 9720 and 10201, were studied at diagnosis for NPM1, FLT3, CEBPA, and WT1 mutations, and gene- and microRNA-expression profiles.Patients with NPM1 mutations (56%) had higher complete remission (CR) rates (84% v 48%; P < .001) and longer disease-free survival (DFS; P = .047; 3-year rates, 23% v 10%) and overall survival (OS; P < .001; 3-year rates, 35% v 8%) than NPM1 wild-type patients. In multivariable analyses, NPM1 mutations remained independent predictors for higher CR rates (P < .001) and longer DFS (P = .004) and OS (P < .001), after adjustment for other prognostic clinical and molecular variables. Unexpectedly, the prognostic impact of NPM1 mutations was mainly observed in patients >or= 70 years. Gene- and microRNA-expression profiles associated with NPM1 mutations were similar across older patient age groups and similar to those in younger (< 60 years) patients with CN-AML. These profiles were characterized by upregulation of HOX genes and their embedded microRNAs and downregulation of the prognostically adverse MN1, BAALC, and ERG genes.NPM1 mutations have favorable prognostic impact in older patients with CN-AML, especially those age >or= 70 years. The gene- and microRNA-expression profiles suggest that NPM1 mutations constitute a marker defining a biologically homogeneous entity in CN-AML that might be treated with specific and/or targeted therapies across age groups.