tbuckley/cabot-search huggingface dataset:
Interleukin 3 stimulates proliferation and triggers endothelial-leukocyte adhesion molecule 1 gene activation of human endothelial cells.
Authors: M F Brizzi, G Garbarino, P R Rossi, G L Pagliardi, C Arduino, G C Avanzi, L Pegoraro
Journal: Journal of Clinical Investigation (1993)

Proliferation and functional activation of endothelial cells within a tissue site of inflammation are regulated by humoral factors released by cells, such as T lymphocytes and monocytes, infiltrating the perivascular space. In the present study we investigated the effects of interleukin 3 (IL-3), an activated T lymphocyte-derived cytokine, on cultured human umbilical vein endothelial cells (HUVEC). Proliferative activity, evaluated both by estimation of the fraction of cells in the S phase and by direct cell count demonstrated that IL-3, at the dose of 25 ng/ml, enhances more than threefold both DNA synthesis and cell proliferation above baseline control conditions. Binding studies with radioiodinated ligand demonstrated that HUVEC constitutively express a smaller number of IL-3 binding sites (approximately 99 binding sites per cell, with an apparent Kd of 149 pM). Accordingly, molecular analysis showed the presence of transcripts for both alpha and beta subunits of the IL-3 receptor. Functional activation of endothelial cells was evaluated by the expression of the endothelial-leukocyte adhesion molecule 1 (ELAM-1) transcript and by leukocyte adhesion. The ELAM-1 gene transcript was clearly detectable 4 h after IL-3 addition and started to decrease after 12 h. Moreover, IL-3-induced ELAM-1 transcription was followed by enhanced adhesion of neutrophils and CD4+ T cells to HUVEC. The findings that IL-3 can stimulate both proliferation and functional activation of endothelial cells suggest that this cytokine can be involved in sustaining the process of chronic inflammation.
Abstract LB-208: Targeting resistance pathways in BRAF-mutant pediatric gliomas
Authors: Tsun-Wen (Sheena) Yao, Yasuyuki Yoshida, Jie Zhang, Tomoko Ozawa, David James, Theodore Nicolaides
Journal: Cancer Research (2014)

Abstract Mutational activation of BRAF is a common finding in pediatric gliomas. As many as 14% of pediatric high grade glioma and up to 66% of certain low grade pediatric glioma subtypes contain the BRAFV600E mutation. Small molecule inhibitors that selectively target BRAFV600E are FDA approved for melanoma and have shown significant efficacy in treating BRAFV600E glioma in pre-clinical trials. Despite showing initial efficacy, drug resistance significantly limits the use of BRAFV600E inhibitors in clinical settings. Here, we identified the molecular mechanisms of BRAFV600E inhibitor resistance in glioma and also provide strategies to over come drug resistance. We have generated multiple BRAFV600E inhibitor resistant glioma cell lines and murine models to study the mechanisms of drug resistance in glioma. The BRAFV600E inhibitor resistant AM38 and DBTRG-05MG cells are insensitive to BRAF inhibitor induced MAP kinase inhibition, reduced cell viability and cell cycle arrest. Also, the BRAFV600E inhibitor resistant glioma xenografts do not respond to drug induced suppression of tumor growth, resulting in poor animal survival. By phospho-receptor tyrosine kinase array and gene expression array, we found that certain receptor tyrosine kinases, including EGF and Axl receptors, and pro-survival pathways such as Wnt signaling, are hyperactivated in BRAFV600E inhibitor resistant gliomas. We further showed that pharmacological and genetic inhibition of those pathways significantly reduces the viability of those drug resistant cells. In conclusion, we have discovered mechanisms of BRAFV600E inhibitor resistance in glioma. We showed that BRAFV600E inhibitor resistant cells acquire drug dependency by upregulating pro-survival pathway, such as Wnt, and hyperactivating receptor tyrosine kinases, including EGFR and Axl, to bypass the insult from the drug. Our data suggests novel therapeutic strategies to BRAFV600E -mutant pediatric glioma in which no effective treatment is available. Citation Format: Tsun-Wen (Sheena) Yao, Yasuyuki Yoshida, Jie Zhang, Tomoko Ozawa, David James, Theodore Nicolaides. Targeting resistance pathways in BRAF-mutant pediatric gliomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-208. doi:10.1158/1538-7445.AM2014-LB-208
Medullary Hyperplastic Hematopoiesis in Thalassemia: Incidental Increased Tc-99m Sestamibi Bone Marrow Uptake
Authors: Giuseppe Villa, Luigi Tommasi, Barbara Colombo, Enrico Balleari
Journal: Clinical Nuclear Medicine (2005)

A 62-year-old, previously healthy white man was referred to our hospital for the recent onset of lumbar pain and the presence in the serum of monoclonal IgG. Clinical workup was planned to ascertain the presence of a clinically relevant monoclonal gammopathy. Tc-99m sestamibi whole-body scintigraphy showed diffusely increased bone marrow uptake. Further laboratory tests were diagnostic for the presence of a beta-thalassemia trait with a concomitant monoclonal gammopathy of undetermined significance. The possibility of concomitant nonmalignant marrow sestamibi uptake must be considered in the clinical assessment of patients with monoclonal gammopathies.
Abstract 3108: Copy number variation analysis in neuroblastoma through next generation sequencing data and SNP-microarray
Authors: Susanne Fransson, Malin Östenssson, Anna Djos, Niloufar Javanmardi, Per Kogner, Tommy Martinsson
Journal: Cancer Research (2014)

Abstract The childhood cancer neuroblastoma show high degree of clinical heterogeneity ranging from aggressive tumors with fatal outcome to cases of spontaneous regression. Analysis of recurrent chromosomal aberrations such as losses of 1p, 11q, gain of 1q, 17q and/or MYCN amplification are currently used for patient stratification and definition of therapeutic strategy. Different analysis techniques for detection of segmental abnormalities include FISH, CGH-microarrays or multiplex ligation-dependent probe amplification (MLPA). However, as next-generation sequencing (NGS) becomes available for clinical use, this could also be used for assessment of copy number alterations simultaneously with mutational analysis. In this study we compare genomic profiles generated through the bioinformatical tool Control-FREEC on Exome sequencing data with profiles generated from Affymetrix 250K or 50K SNP-microarrays on 20 NB tumors of different stages. Exome sequencing was performed by paired-end sequencing on Illumina instrumentation after DNA enrichment with Agilent SureSelect All Exome. The sequencing were performed at three separate occasions with a median raw coverage of 91X, 127X and 340X respectively. Neuroblastoma tumors were normalized with either corresponding constitutional DNA or normal control DNA for NGS data while microarrays were normalized against healthy control DNA. Gross genomic changes were extracted through visual and/or ratio inspection from 20 neuroblastoma tumors. A total of 128 larger segmental aberrations and 63 numerical aneuploidies were detected trough SNP-microarrays. Discrepancies between the two methods were detected in three cases; one segmental loss detected through microarray could not be confirmed by NGS-profiling, one smaller deletion were only detected through NGS-profiling and in one instance both methods indicated 2p-gain but at different positions. Otherwise the results were concordant. Furthermore, through exome sequencing data were we also able to detect ALK mutations in four patients, ATRX-deletions in two patients and chromothripsis of chromosome 5 in one patient. In conclusion, exome sequencing could be used as a new diagnostic tool for neuroblastoma tumors combining mutational screening with detection of common chromosomal and segmental aneuploidies such as 2p-gain, 17q-gain, 11q-deletion as well as MYCN-amplification and alterations of ALK or ATRX. Citation Format: Susanne Fransson, Malin Östenssson, Anna Djos, Niloufar Javanmardi, Per Kogner, Tommy Martinsson. Copy number variation analysis in neuroblastoma through next generation sequencing data and SNP-microarray. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3108. doi:10.1158/1538-7445.AM2014-3108
Cervical Paraganglioma Mimicking a Parathyroid Adenoma on Tc-99m Sestamibi Scintigraphy
Authors: Anish Bhattacharya, Bhagwant Rai Mittal, Anil Bhansali, Bishan Das Radotra, Arunanshu Behera
Journal: Clinical Nuclear Medicine (2006)

A 32-year-old man with a clinical and biochemical profile suggestive of primary hyperparathyroidism presented with a soft tissue mass on the left side of the neck. Multiphasic planar and SPECT Tc-99m sestamibi (MIBI) scintigraphy showed focally increased tracer concentration in the mass. Subsequent histopathology and immunostaining identified the mass as a parathyroid hormone-secreting cervical paraganglioma, indicating that this tumor should be considered in the differential interpretation of MIBI concentration in the neck.
Precise glioma targeting of and penetration by aptamer and peptide dual-functioned nanoparticles
Authors: Huile Gao, Jun Qian, Shijie Cao, Zhi Yang, Zhiqing Pang, Shuaiqi Pan, Li Fan, Zhangjie Xi, Xinguo Jiang, Qizhi Zhang
Journal: Biomaterials (2012)
Hepatitis B Infection in Patients With Acute Liver Failure in the United States
Authors: Eng-Kiong Teo, George Ostapowicz, Munira Hussain, William M. Lee, Robert J. Fontana, Anna S.F. Lok
Journal: Hepatology (2001)

Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR–positive samples were sequenced. Sera and/or liver from 139 patients (39 males, 100 females; mean age, 42 years) enrolled between January 1998 and December 1999 were studied. Twelve patients were diagnosed with hepatitis B, 1 with hepatitis B+C+D coinfection, and 22 had indeterminate etiology. HBV DNA was detected in the sera of 9 (6%) patients; all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore and/or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non–B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. HBV precore and/or core promoter variants were common among US patients with ALF caused by hepatitis B. (Hepatology 2001;33:972–976.)
Bacteria killer found in sweat
Authors: D. Josefson
Journal: BMJ (2001)

Human sweat is capable of warding off more than potential friends and lovers.

Researchers at Eberhard-Karls University in Tubingen, Germany, have isolated a new antibiotic, dubbed dermcidin, which is secreted in sweat and may serve as a first line of defence against microbial pathogens.

Dermcidin's structure differs from known antibiotics and may kill micro-organisms by a different mechanism. The work has been published in the online edition of Nature Immunology (www.nature.com/ni) in advance of the print edition.

Dr Birgit Schittek and her colleagues from the university's departments of oncological dermatology, immunology, molecular biology, and genetics stumbled serendipitously on the dermcidin gene while screening DNA libraries from melanoma and naevus cell …
Double-Outlet Right Ventricle with Intact Interventricular Septum
Authors: H. EDWARD MACMAHON, MICHAEL LIPA
Journal: Circulation (1964)

This case is one of a 3-month-old infant showing complete transposition of the aorta, with both great vessels arising from the right ventricle. Of particular interest was the absence of a patent interventricular septum. A single but quite inadequate opening in the interatrial septum was the only visible means by which oxygenated blood from the lungs could reach the systemic circulation. No identical case has been found in the literature.
A piece of my mind. On his shoulders
Authors: M. B. Parker
Journal: JAMA (1989)

I grew up thinking—like many other kids—that my dad was wonderful. My brothers and sisters and I would sit in our tree house as he mowed the lawn around us, surprising us by reaching up to grab a toe that had been dangling precariously over the edge. He and my mother took us on long driving trips, showing us national parks and state beaches, snow in August in Washington State, the phosphorescence in the Pacific waves. Because I was the youngest, I was always carried on his shoulders as we hiked. I remember vividly hearing him whistle to the birds, and the bright red cap my mother knitted that he always wore. "With this on," he said, "you'll always be able to find me if you wander off." And there was his work. He left the house before I awoke, to go to "my dad's hospital" to do something I
Medical response to radiation incidents and radionuclear threats
Authors: István Turai, Katalin Veress, Bengül Günalp, Gennadi Souchkevitch
Journal: BMJ (2004)

Events that expose people to radiation are rare, but the threat of radiation injury is increasing. Doctors should know how to recognise and manage suspected exposure or contamination 

After the attacks of 11 September 2001, use of sources of radiation by terrorists with the potential to cause human damage has become a greater threat.1–4 Various professionals have discussed whether malevolent use of these sources could result in radiation sickness or radiation injuries on a large scale and the possible results.5–7 Radiation sickness is the acute or delayed consequences of exposure of the whole body or a large part to high doses of ionising radiation capable of causing a set of non-specific clinical symptoms and haematological changes. Radiation injury is the acute or delayed consequences of exposure of a small part of the body to high doses of ionising radiation capable of causing burns or other localised organ pathology—for example, cataract, hypothyreosis, and pneumonia.

Responses to recent incidents involving radiation indicate that most general practitioners are uncertain about the health consequences of exposure to ionising radiation and the medical management of exposed patients.8–10

Clinical manifestations of pathological changes depend on the size of the exposed area of the body. The severity of symptoms depends on the absorbed dose of radiation by the exposed area of the body.

The medical community needs to consider this issue because of the need for emergency medical care after a possible use of radionuclear materials by terrorists.11 12

Medical education and postgraduate training programmes for primary care doctors worldwide seem to lack the appropriate information about radiation incidents as regards recognition, differential diagnosis, and first medical response.7 13 14 We aim to advise on the basic medical management of radiation sickness and radiation injuries, and …
The Structure of Water and Electrolyte Solutions
Authors: RICHARD J. PODOLSKY
Journal: Circulation (1960)

Intermolecular forces tend to organize water molecules into a tetrahedral lattice, conferring "crystalline" properties on the liquid. The simple ions, such as Na + , K + , and Cl - , have dimensions which are of the same order as the water molecule. Therefore, in aqueous solution, ions can substitute for water molecules in the water lattice. However, because the force between ion and water molecule differs from the force between 2 water molecules, the properties of the lattice are perturbed by an ion. Transport processes in electrolyte solutions are analyzed in terms of the specific lattice perturbation produced by each ion. This approach is contrasted with the classical hydrodynamic model in which ions in solution are treated as spheres in a continuous fluid. The relevance of ionic transport in aqueous solution to the transport across biologic membranes is briefly discussed.
The Budd-Chiari Syndrome in Sarcoidosis
Authors: Michael R. Natalino, Richert E. GOYETTE, Loren C. Owensby, Ronald N. Rubin
Journal: JAMA (1978)

<h3>To the Editor.—</h3> Hepatic involvement by sarcoidosis is well known. The most common manifestation is a noncaseating granulomatous hepatitis.<sup>1</sup>Associated findings may include chronic intrahepatic cholestasis, periportal fibrosis, and eventual development of a micronodular cirrhosis.<sup>1</sup>To our knowledge, hepatic-vein thrombosis (Budd-Chiari syndrome) has not been encountered as a complication of sarcoidosis. We recently studied a patient with sarcoidosis in whom acute hepatic-vein thrombosis occurred in the absence of other underlying causes. <h3>Report of a Case.—</h3> A 19-year-old black man was admitted for evaluation of abdominal pain, weight loss, night sweats, and an abnormal chest roentgenogram. Systems review showed a history of sickle cell trait but no prior sickle cell crises or prior abdominal trauma. Physical findings included hepatomegaly, splenomegaly, and a maculopapular, hyperpigmented rash on the chest and legs. Chest roentgenograms showed bilateral hilar lymphadenopathy. Pertinent laboratory values included alkaline phosphatase, 315 IU; total bilirubin, 2.8 mg/dl; hematocrit,
A9.11 Anti-apolipoprotein A1 autoantibodies induce tissue factor activity and expression: a role in atherothrombosis
Authors: Sabrina Pagano, Julien Virzi, Nathalie Satta, Tiphaine Mannic, Pascale Roux-Lombard, François Mach, Fabrizio Montecucco, Nicolas Vuilleumier
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Introduction</h3> Autoimmune-mediated inflammation may play a role in atherosclerosis and atherothrombosis, essential features for cardiovascular disease (CVD) manifestations. Anti-Apolipoprotein A-1 (ApoA-1) IgG autoantibodies are an independent predictor of poor cardiovascular outcome in different clinical settings, promote inflammation and atherogenesis and are associated with increased atherosclerotic plaque vulnerability in humans and mice. <h3>Aim</h3> To determine whether anti-ApoA-1 IgG are associated with Tissue Factor (TF) expression, a key regulator of the extrinsic coagulation pathway involved in atherothrombosis, responsible for the majority of acute CVD manifestations. <h3>Methods</h3> Atherothrombosis features were explored <i>in vivo</i> by immunohistochemical TF staining on human carotid atherosclerotic plaques from (n = 102) patients with severe carotid stenosis and <i>in vitro,</i> on human monocyte derived macrophages (HMDM), TF expression and pro-coagulant activity detected by cytofluorimetry and chromogenic assay respectively. <h3>Results</h3> <i>In vivo</i> atherosclerotic biopsies derived from patients with high circulating levels of anti-apoA-1 IgG (n = 20) displayed a higher TF expression when compared to biopsies from patients with low anti-apoA-1 IgG levels (9.3% vs 3.3%, p&lt;0.0001). Spearman correlation reported a significant association between the circulating levels of those autoantibodies and TF expression (r = 0.41, p&lt;0.001), as well as between CD68 atherosclerotic plaque expression and TF expression (r = 0.33, p = 0.004). On HMDM, anti-ApoA-1 IgG induced a significant dose-dependent increase in TF expression and a pro-coagulant activity only in supernatants and cells treated with anti-ApoA-1 IgG (p = 0.02, p&lt;0.0001, p = 0.0006 respectively). <h3>Conclusions</h3> We demonstrated that anti-ApoA-1 IgG are associated with higher propensity to atherothrombosis, the <i>in vitro</i> results suggest they could per se induce TF expression, supporting a possible causal link between anti-ApoA-1 IgG and atherothrombosis.
Onan's Act-Reply
Authors: Joseph L. Jorizzo
Journal: JAMA (1984)

In Reply.—  We greatly appreciate Dr Waldman's comments. We are aware of the biblical controversy that he reviews. However, Dorland's Medical Dictionary does list onanism and masturbation as synonyms. I am more concerned, however, with Dr Waldman's suggested appellation, factitial frictional dermatitis of the penis . The history of the diagnosis factitial dermatitis in dermatology has been filled with controversy. Current dermatologic opinion regarding self-induced cutaneous disease favors separating cutaneous artifactual disease (contrived disease) from clinicopathologic entities such as lichen simplex chronicus and prurigo nodularis, which often are the result of compulsive habit and are not contrived. 1-3 If the term factitial dermatitis . is used at all, it is usually as a synonym for cutaneous artifactual disease. The correct dermatologic diagnosis for our patients, as stated in our original letter, was lichen simplex chronicus of the penis; however, we continue also to use the not totally accurate, but quaint, appellation frictional
S3 Work performance and airflow obstruction in a general UK population of older workers
Authors: J. Szram, S. J. Schofield, A. P. M. Woods, N. Crisp, D. Harris, P. Cullinan
Journal: Thorax (2011)

<h3></h3> Work disability as a consequence of COPD has been found in a number of patient cohorts and respiratory symptoms were shown to be significantly associated with work limitation in the Lungs at Work study.1 The impact of airflow obstruction on impaired work performance in the general population is unknown. The clinical assessment was designed to examine the relationship between respiratory symptoms and work performance in a general population of older workers in more detail. Volunteers in full time employment at the time of the initial postal questionnaire study (of 51 to 60-year olds through general practice) underwent clinical assessment, including spirometry (n=1773). Results are shown in Abstract S3 table 1. Prevalence of declared doctor-diagnosed COPD was low (1.9% of men and 0.6% of women) compared to that of airflow obstruction on spirometry (post-bronchodilator FEV<sub>1</sub>&lt;80% predicted and FEV<sub>1</sub>/FVC ratio&lt;0.7) was higher, similar to previous published estimates. Men and women with airflow obstruction had a significantly higher prevalence of poor self-reported performance at work than individuals with normal spirometry. Subjects of both sexes with abnormal spirometry who also reported high levels of physical activity in their current job were significantly more likely to report poor work performance than individuals without airflow obstruction with similarly high activity levels; this difference was not seen in low activity work (data not shown). Men were significantly more likely than women to predict that they would stop work due to ill-health. In both sexes, participants with abnormal spirometry were significantly more likely to predict ill-health retirement than individuals with normal lung function. This study has demonstrated an association between airflow obstruction and both work performance within a general population of older workers; the level of physical activity required at work had an important effect on this relationship. Future loss from the workforce due to ill-health was also related to lung function. Detection of airflow obstruction could aid retention in employment, provided that suitable interventional strategies are in place to support older workers.