tbuckley/cabot-search huggingface dataset:
Incidence of antiretinal antibodies in melanoma: screening of 77 serum samples from 51 patients with American Joint Committee on Cancer stage I-IV
Authors: G. Ladewig, U. Reinhold, C.E. Thirkill, A. Kerber, W. Tilgen, C. Pfohler
Journal: British Journal of Dermatology (2005)

Background Patients with melanoma‐associated retinopathy (MAR) experience different visual symptoms caused by the production of antitumoral antibodies that cross‐react with retinal epitopes. Immunofluorescence assays of serum from patients with MAR on sectioned monkey or human retina characteristically reveal antibody activity located within the inner nuclear layer, with a focus of activity upon the membranes of bipolar cells. Objectives We inquired into the association with disease of this serological abnormality by evaluating sera from patients with melanoma with no MAR‐like signs or symptoms. Methods Groups of patients were selected with different stages of melanoma (American Joint Committee on Cancer stages I–IV). Seventy‐seven serum samples from 51 patients with melanoma were examined by indirect immunohistochemical assay on sections of human retina. Results Of the 77 serum samples, 53 were found to contain antibodies reactive with various components of retina. Eight were from 17 sera from patients in stage I or II, 14 were from 23 sera from patients in stage III, and 31 were from 37 sera from patients in stage IV. Statistical analysis revealed a correlation between antibody activity and the stage of disease, with a higher percentage of antibody activity in advanced stages (P = 0·002). Conclusions The presence of antiretinal antibodies in patients with melanoma without ocular symptoms appears to be more common than previously suspected. Antibody activity similar to that ascribed to the MAR syndrome appears in some patients with melanoma who have no MAR‐like retinopathy. Follow‐up studies will determine if patients with antiretinal antibodies go on to develop MAR and if staining intensity and staining patterns change over the course of the disease.
Neuroendocrine Neoplasms of the Lung: A Prognostic Spectrum
Authors: Hisao Asamura, Toru Kameya, Yoshihiro Matsuno, Masayuki Noguchi, Hirohito Tada, Yuichi Ishikawa, Tomoyuki Yokose, Shi-Xu Jiang, Takeshi Inoue, Ken Nakagawa, Kinuko Tajima, Kanji Nagai
Journal: Journal of Clinical Oncology (2005)

Neuroendocrine (NE) tumors of the lung include typical carcinoid (TC), atypical carcinoid (AC), large-cell NE carcinoma (LCNEC), and small-cell lung carcinoma (SCLC). Their clinicopathologic profiles and relative grade of malignancy have not been defined.From 10 Japanese institutes, 383 surgically resected pulmonary NE tumors were collected. The histologic diagnosis was determined by the consensus of a pathology panel consisting of six expert pathologists as TC, AC, LCNEC, or SCLC on the basis of the WHO classification, and its relationship to clinicopathologic profiles was analyzed.Of the 383 tumors, 18 were excluded because of an improper specimen. The pathology panel reviewed the remaining 366 tumors, and a diagnosis of NE tumor was made in 318 patients (87.4%); 55 patients had TC, nine had AC, 141 had LCNEC, and 113 had SCLC. The 5-year survival rates of patients with all stages were as follows: 96.2% for TC, 77.8% for AC, 40.3% for LCNEC, and 35.7% for SCLC. There was significant prognostic difference between TC and AC as well as between AC and LCNEC+SCLC. However, there was no difference between LCNEC and SCLC, and their survival curves were superimposed. The multivariate analysis indicated that histologic type, completeness of resection, symptoms, nodal involvement, and age were significantly prognostic.The grade of malignancy of NE tumors was upgraded in the following order: TC, AC, LCNEC, and SCLC. No prognostic difference was noted between LCNEC and SCLC. The high-grade NE histology uniformly indicated poor prognosis regardless of its histologic type.
IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis
Authors: A. I. Kaplin
Journal: Journal of Clinical Investigation (2005)

Transverse myelitis (TM) is an immune-mediated spinal cord disorder associated with inflammation, demyelination, and axonal damage. We investigated the soluble immune derangements present in TM patients and found that IL-6 levels were selectively and dramatically elevated in the cerebrospinal fluid and directly correlated with markers of tissue injury and sustained clinical disability. IL-6 was necessary and sufficient to mediate cellular injury in spinal cord organotypic tissue culture sections through activation of the JAK/STAT pathway, resulting in increased activity of iNOS and poly(ADP-ribose) polymerase (PARP). Rats intrathecally infused with IL-6 developed progressive weakness and spinal cord inflammation, demyelination, and axonal damage, which were blocked by PARP inhibition. Addition of IL-6 to brain organotypic cultures or into the cerebral ventricles of adult rats did not activate the JAK/STAT pathway, which is potentially due to increased expression of soluble IL-6 receptor in the brain relative to the spinal cord that may antagonize IL-6 signaling in this context. The spatially distinct responses to IL-6 may underlie regional vulnerability of different parts of the CNS to inflammatory injury. The elucidation of this pathway identifies specific therapeutic targets in the management of CNS autoimmune conditions.
Disruption of Endothelial Cell Interactions with the Novel HU177 Cryptic Collagen Epitope Inhibits Angiogenesis
Authors: Alexandra Cretu, Jennifer M. Roth, Maresa Caunt, Abebe Akalu, Desiree Policarpio, Silvia Formenti, Paul Gagne, Leonard Liebes, Peter C. Brooks
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The importance of cellular communication with the extracellular matrix in regulating cellular invasion is well established. Selective disruption of communication links between cells and the local microenvironment by specifically targeting non-cellular matrix-immobilized cryptic extracellular matrix epitopes may represent an effective new clinical approach to limit tumor-associated angiogenesis. Therefore, we sought to determine whether the HU177 cryptic collagen epitope plays a functional role in regulating angiogenesis in vivo. Experimental Design: We examined the expression and characterized the HU177 cryptic collagen epitope in vitro and in vivo using immunohistochemistry and ELISA. We examined potential mechanisms by which this cryptic collagen epitope may regulate angiogenesis using in vitro cell adhesion, migration, proliferation, and biochemical assays. Finally, we examined the whether blocking cellular interactions with the HU177 cryptic epitope plays a role in angiogenesis and tumor growth in vivo using the chick embryo model. Results: The HU177 cryptic epitope was selectively exposed within tumor blood vessel extracellular matrix, whereas little was associated with quiescent vessels. An antibody directed to this cryptic site selectively inhibited endothelial cell adhesion, migration, and proliferation on denatured collagen type IV and induced increased levels of cyclin-dependent kinase inhibitor p27KIP1. Systemic administration of mAb HU177 inhibited cytokine- and tumor-induced angiogenesis in vivo. Conclusions: We provide evidence for a new functional cryptic regulatory element within collagen IV that regulates tumor angiogenesis. These findings suggest a novel and highly selective approach for regulating angiogenesis by targeting a non-cellular cryptic collagen epitope.
Gene ontology analysis for RNA-seq: accounting for selection bias
Authors: Matthew D Young, Matthew J Wakefield, Gordon K Smyth, Alicia Oshlack
Journal: Genome biology (2010)

Abstract We present GOseq, an application for performing Gene Ontology (GO) analysis on RNA-seq data. GO analysis is widely used to reduce complexity and highlight biological processes in genome-wide expression studies, but standard methods give biased results on RNA-seq data due to over-detection of differential expression for long and highly expressed transcripts. Application of GOseq to a prostate cancer data set shows that GOseq dramatically changes the results, highlighting categories more consistent with the known biology.
Treatment of Depression by Drugs and Psychotherapy
Authors: GERALD L. KLERMAN, ALBERTO DIMASCIO, MYRNA WEISSMAN, BRIGITTE PRUSOFF, EUGENE S. PAYKEL
Journal: American Journal of Psychiatry (1974)

Prevention of relapse following depression is a pressing research problem. The authors tested the efficacy of the tricyclic antidepressant amitriptyline and psychotherapy, alone and in combination, in preventing the relapse of 150 neurotic depressed female patients. They found that patients receiving amitriptyline and little psychotherapy had a 12-percent relapse rate, compared to a 16-percent rate for those receiving more psychotherapy and no medication. There was no significant difference between drug therapy alone or drug therapy in combination with psychotherapy. However, psychotherapy was beneficial to patients with problems of social adjustment and interpersonal relations. The need for further research and implications for treatment are discussed.
<i>SOX2</i> Expression Associates with Stem Cell State in Human Ovarian Carcinoma
Authors: Petra M. Bareiss, Anna Paczulla, Hui Wang, Rebekka Schairer, Stefan Wiehr, Ursula Kohlhofer, Oliver C. Rothfuss, Anna Fischer, Sven Perner, Annette Staebler, Diethelm Wallwiener, Falko Fend, Tanja Fehm, Bernd Pichler, Lothar Kanz, Leticia Quintanilla-Martinez, Klaus Schulze-Osthoff, Frank Essmann, Claudia Lengerke
Journal: Cancer Research (2013)

The SRY-related HMG-box family of transcription factors member SOX2 regulates stemness and pluripotency in embryonic stem cells and plays important roles during early embryogenesis. More recently, SOX2 expression was documented in several tumor types including ovarian carcinoma, suggesting an involvement of SOX2 in regulation of cancer stem cells (CSC). Intriguingly, however, studies exploring the predictive value of SOX2 protein expression with respect to histopathologic and clinical parameters report contradictory results in individual tumors, indicating that SOX2 may play tumor-specific roles. In this report, we analyze the functional relevance of SOX2 expression in human ovarian carcinoma. We report that in human serous ovarian carcinoma (SOC) cells, SOX2 expression increases the expression of CSC markers, the potential to form tumor spheres, and the in vivo tumor-initiating capacity, while leaving cellular proliferation unaltered. Moreover, SOX2-expressing cells display enhanced apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence, our data show that SOX2 associates with stem cell state in ovarian carcinoma and induction of SOX2 imposes CSC properties on SOC cells. We propose the existence of SOX2-expressing ovarian CSCs as a mechanism of tumor aggressiveness and therapy resistance in human SOC.
Renal effects of acute isosorbide-5-mononitrate administration in cirrhosis
Authors: Joan M. Salmerón, Luis Ruiz Del Arbol, Angels Ginès, Joan C. García-Pagán, Pere Ginés, Faust Feu, Joan Claria, Francisca Rivera, Jaume Bosch, Vicente Arroyo, Joan Rodés
Journal: Hepatology (1993)

The aim of this study was to assess the effects of an oral dose (20 mg) of isosorbide-5-mononitrate on systemic hemodynamics, kidney function, plasma renin activity and plasma aldosterone and atrial natriuretic peptide concentrations in 16 nonazotemic cirrhotic patients. Isosorbide-5-mononitrate significantly reduced cardiopulmonary pressures, cardiac output, peripheral vascular resistance, mean arterial pressure, renal-plasma flow, glomerular filtration rate, free water clearance, sodium excretion and atrial natriuretic peptide concentration and significantly increased renin and aldosterone values. Cardiopulmonary pressures, atrial natriuretic peptide, cardiac output and mean arterial pressure decreased to a similar extent in patients with (n = 9) and without ascites (n = 7). In patients with ascites we noted marked increases in plasma renin activity (3.7 ± 1.1 ng/ml/hr to 6.4 ± 1.8 ng/ml/hr; p = 0.01) and aldosterone level (61.1 ± 17.5 ng/dl to 108.4 ± 36.1 ng/dl; p = 0.01). In contrast, in patients without ascites the elevation of plasma renin activity (0.5 ± 0.16 ng/ml/hr to 0.95 ± 0.27 ng/ml/hr; p = 0.02) and aldosterone level (5.9 ± 1.3 ng/dl to 12.3 ± 3.8 ng/dl; p = 0.02) was mild, and in no case did these parameters increase over the upper normal limit. Isosorbide-5-mononitrate produced a significantly greater reduction of glomerular filtration rate (-21.4% ± 3.3% vs. −8.9% ± 4.2%; p = 0.03) and free water clearance (−82.4% ± 16.1% vs. −34.5% ± 12.3%; p = 0.03) in patients with ascites than in those without. We also saw a trend toward a greater decrease of renal plasma flow in ascitic patients (−29.2% ± 7.1% vs. −9.8% ± 9.8%; p = 0.1). Urinary sodium excretion showed a similar decrease (−43.7% ± 9.8% vs. −56.7% ± 12.5%) in the two groups. These results indicate that the administration of a single oral dose of isosorbide-5-mononitrate stimulates the renin-aldosterone system and impairs kidney function in patients with cirrhosis, especially in those with ascites. (Hepatology 1993;17:800-806.)
Effects of High Carbohydrate or Protein Diets on Blood Pressure of Normotensive and Hypertensive Dogs
Authors: C. M. WILHELMJ, V. W. MEYERS, H. H. MCCARTHY
Journal: Circulation Research (1958)

The effects of diets high in carbohydrate or protein were studied on four dogs when normotensive and later when hypertensive. The results suggest that under certain conditions a cardiovascular homeostatic relationship may exist between diet, VEM-VDM and the sympathicoadrenal system.
Systemic Delivery of Bone Marrow–Derived Mesenchymal Stem Cells to the Infarcted Myocardium
Authors: Israel M. Barbash, Pierre Chouraqui, Jack Baron, Micha S. Feinberg, Sharon Etzion, Ariel Tessone, Liron Miller, Esther Guetta, Dov Zipori, Laurence H. Kedes, Robert A. Kloner, Jonathan Leor
Journal: Circulation (2003)

Systemic delivery of bone marrow-derived mesenchymal stem cells (BM-MSCs) is an attractive approach for myocardial repair. We aimed to test this strategy in a rat model after myocardial infarction (MI).BM-MSCs were obtained from rat bone marrow, expanded in vitro to a purity of >50%, and labeled with 99mTc exametazime, fluorescent dye, LacZ marker gene, or bromodeoxyuridine. Rats were subjected to MI by transient coronary artery occlusion or to sham MI. 99mTc-labeled cells (4x10(6)) were transfused into the left ventricular cavity of MI rats either at 2 or 10 to 14 days after MI and were compared with sham-MI rats or MI rats treated with intravenous infusion. Gamma camera imaging and isolated organ counting 4 hours after intravenous infusion revealed uptake of the 99mTc-labeled cells mainly in the lungs, with significantly smaller amounts in the liver, heart, and spleen. Delivery by left ventricular cavity infusion resulted in drastically lower lung uptake, better uptake in the heart, and specifically higher uptake in infarcted compared with sham-MI hearts. Histological examination at 1 week after infusion identified labeled cells either in the infarcted or border zone but not in remote viable myocardium or sham-MI hearts. Labeled cells were also identified in the lung, liver, spleen, and bone marrow.Systemic intravenous delivery of BM-MSCs to rats after MI, although feasible, is limited by entrapment of the donor cells in the lungs. Direct left ventricular cavity infusion enhances migration and colonization of the cells preferentially to the ischemic myocardium.
Population genetical musings on suicidal behavior as a common, harmful, heritable mental disorder
Authors: Martin Voracek
Journal: Behavioral and Brain Sciences (2006)

Suicidal behavior is an interesting blank space in Keller &amp; Miller's (K&amp;M's) population genetical account on explaining the existence and persistence of common, harmful, heritable mental disorders. I argue that suicidal behavior is yet another of these disorders. It may well be consistent with all three evolutionary models considered by K&amp;M.
Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens
Authors: Yan Zheng, Patricia A Valdez, Dimitry M Danilenko, Yan Hu, Susan M Sa, Qian Gong, Alexander R Abbas, Zora Modrusan, Nico Ghilardi, Frederic J de Sauvage, Wenjun Ouyang
Journal: Nature Medicine (2008)
Topology and Dynamics of Signaling Networks: In Search of Transcriptional Control of the Inflammatory Response
Authors: Ioannis P. Androulakis, Kubra Kamisoglu, John S. Mattick
Journal: Annual Review of Biomedical Engineering (2013)

Over the past several decades, to develop a fundamental understanding of inflammation's progression, research has focused on extracellular mediators, such as cytokines, as characteristic components of inflammatory response. These efforts have recently been complemented by advances in proteomics that allow analysis of multiple signaling proteins in parallel, to provide more complete mechanistic models of inflammation. In this review, we discuss various techniques for assessing protein activity, as well as computational techniques that are well suited for interpreting large amounts of proteomic data to generate signaling networks or for modeling the dynamics of known network interactions. We also discuss examples that explore these experimental and computational techniques in tandem to generate signaling networks under various conditions and that link those networks to transcriptional activity. Further advancements in this field will likely provide an explicit description of inflammatory response, paving the way for better diagnostics and therapies in clinic.
Shaping Your Career to Maximize Personal Satisfaction in the Practice of Oncology
Authors: Tait Shanafelt, Harold Chung, Heather White, Laurie Jean Lyckholm
Journal: Journal of Clinical Oncology (2006)

The practice of oncology can be a source of both great satisfaction and great stress. Although many oncologists experience burnout, depression, and dissatisfaction with work, others experience tremendous career satisfaction and achieve a high overall quality of life. Identifying professional goals, optimizing career fit, identifying and managing stressors specific to practice type, and achieving the optimal personal work-life balance can increase the likelihood of individual oncologists' achieving personal and professional satisfaction. In this article, we will explore how oncologists can accomplish these tasks and will examine several pervasive professional myths that often distort perspective. The article concludes in a conversation with four oncologists regarding what they find most meaningful about their work, how they manage career-specific stressors, and how they achieve balance between their personal and professional lives.
Links Among Human Health, Animal Health, and Ecosystem Health
Authors: Peter Rabinowitz, Lisa Conti
Journal: Annual Review of Public Health (2013)

In the face of growing world human and animal populations and rapid environmental change, the linkages between human, animal, and environmental health are becoming more evident. Because animals and humans have shared risk to health from changing environments, it seems logical to expand the perspective of public health beyond a single species to detect and manage emerging public health threats. Mitigating the effects of climate change, emerging pathogens, toxicant releases, and changes in the built environment requires a retooling of global public health resources and capabilities across multiple species. Furthermore, human and animal health professionals must overcome specific barriers to interprofessional collaboration to implement needed health strategies. This review outlines the relationships between human, animal, and ecosystem health and the public health challenges and opportunities that these links present.
Vitamin D as a Public Health Problem
Authors: B. McNicholl
Journal: BMJ (1964)

27 June, p. 1653).I feel that this editorial, perhaps unintentionally, was exceedingly patronizing to both the World Health Organization and to Scotland.Further, it only advanced the arguments supporting the present somewhat negative "party line" and made no effort to review or consider many obvious points that can be made for such a Centre with all ,the three suggested functions-namely, epi- .demiology,communications, and biomedical research.Judging by recent reported state- ments by the Minister of Science and the 'Secretary of State for Scotland, there is now wide acceptance of the first two functions, and, if the W.H.O.proposed such a Centre, then it appears likely that the United King- dom will support an invitation to site the Centre in Scotland.However, your editorial, and since then the Parliamentary Secretary, Ministry of Health, appear strongly opposed to an
Oral 11, Potential life-threatening complications of vascular malformations
Authors: C. Feighery, S.H.E. Hoey, J.R. Corbett, E.A. Bingham
Journal: British Journal of Dermatology (2007)

We present two patients with vascular anomalies which illustrate important learning points. Patient 1 was a 7‐year‐old girl who was being followed up for a vascular malformation which had been present at birth and had slowly enlarged over the years. It was located midline, overlying her thoracic spine. Magnetic resonance (MR) imaging revealed the lesion to be an arteriovenous malformation. An MR angiogram, performed to delineate further the extent of involvement around the spine, surprisingly revealed multiple pulmonary arteriovenous malformations. The patient admitted to having regular nosebleeds but was otherwise asymptomatic and had no telangiectasia on her face or in her mouth. There was no family history of bleeding disorders. Genetic testing has confirmed hereditary haemorrhagic telangiectasia. We present this girl to highlight the significance of midline vascular lesions, which should be treated with suspicion and physicians should have a low threshold for investigation. Patient 2 was an 18‐year‐old man attending the multidisciplinary vascular anomalies clinic with an extensive lymphatic venous malformation present since birth. Imaging showed this involved the bladder and rectum, and extended the whole way down the left leg to include the foot. Over the years he was troubled with haematuria, rectal bleeding, and recurrent painful episodes. D‐dimers were elevated. His condition was complicated by bilateral extensive pulmonary emboli and he was started on low‐molecular‐weight heparin. Despite this he went on to suffer a fatal pulmonary embolus 2 months later. These cases highlight the associated risks of vascular malformations.