tbuckley/cabot-search huggingface dataset:
Id2 Mediates Oligodendrocyte Precursor Cell Maturation Arrest and Is Tumorigenic in a PDGF-Rich Microenvironment
Authors: Matthew C. Havrda, Brenton R. Paolella, Cong Ran, Karola S. Jering, Christina M. Wray, Jaclyn M. Sullivan, Audrey Nailor, Yasuyuki Hitoshi, Mark A. Israel
Journal: Cancer Research (2014)

Maturation defects occurring in adult tissue progenitor cells have the potential to contribute to tumor development; however, there is little experimental evidence implicating this cellular mechanism in the pathogenesis of solid tumors. Inhibitor of DNA-binding 2 (Id2) is a transcription factor known to regulate the proliferation and differentiation of primitive stem and progenitor cells. Id2 is derepressed in adult tissue neural stem cells (NSC) lacking the tumor suppressor Tp53 and modulates their proliferation. Constitutive expression of Id2 in differentiating NSCs resulted in maturation-resistant oligodendroglial precursor cells (OPC), a cell population implicated in the initiation of glioma. Mechanistically, Id2 overexpression was associated with inhibition of the Notch effector Hey1, a bHLH transcription factor that we here characterize as a direct transcriptional repressor of the oligodendroglial lineage determinant Olig2. Orthotopic inoculation of NSCs with enhanced Id2 expression into brains of mice engineered to express platelet-derived growth factor in the central nervous system resulted in glioma. These data implicate a mechanism of altered NSC differentiation in glioma development and characterize a novel mouse model that reflects key characteristics of the recently described proneural subtype of glioblastoma multiforme. Such findings support the emerging concept that the cellular and molecular characteristics of tumor cells are linked to the transformation of distinct subsets of adult tissue progenitors.
Generation of Prostate Tumor–Initiating Cells Is Associated with Elevation of Reactive Oxygen Species and IL-6/STAT3 Signaling
Authors: Yi Qu, Anne Margrete Oyan, Runhui Liu, Yaping Hua, Jigang Zhang, Randi Hovland, Mihaela Popa, Xiaojun Liu, Karl A. Brokstad, Ronald Simon, Anders Molven, Biaoyang Lin, Wei-dong Zhang, Emmet McCormack, Karl-Henning Kalland, Xi-Song Ke
Journal: Cancer Research (2013)

How prostate cancer is initiated remains a topic of debate. In an effort to establish a human model of prostate carcinogenesis, we adapted premalignant human prostate EPT2-D5 cells to protein-free medium to generate numerous tight prostate spheres (D5HS) in monolayer culture. In contrast to EPT2-D5 cells, the newly generated D5HS efficiently formed large subcutaneous tumors and subsequent metastases in vivo, showing the tumorigenicity of D5HS spheres. A striking production of interleukin (IL)-6 mRNA and protein was found in D5HS cells. The essential roles of IL-6 and the downstream STAT3 signaling in D5HS tumor sphere formation were confirmed by neutralizing antibody, chemical inhibitors, and fluorescent pathway reporter. In addition, elevated reactive oxygen species (ROS) produced upon protein depletion was required for the activation of IL-6/STAT3 in D5HS. Importantly, a positive feedback loop was found between ROS and IL-6 during tumor sphere formation. The association of ROS/IL-6/STAT3 to the carcinogenesis of human prostate cells was further examined in xenograft tumors and verified by limiting dilution implantations. Collectively, we have for the first time established human prostate tumor-initiating cells based on physiologic adaption. The intrinsic association of ROS and IL-6/STAT3 signaling in human prostate carcinogenesis shed new light on this relationship and define therapeutic targets in this setting.
Neutrality, Compensation, and Negative Selection during Evolution of B-Cell Development Transcriptomes
Authors: R. Hoffmann, C. Lottaz, T. Kuhne, A. Rolink, F. Melchers
Journal: Molecular Biology and Evolution (2007)

B cells develop in the mammalian bone marrow through a sequence of precursor stages, which can be ordered by the recombination status of their immunoglobulin loci. This developmental pathway is functionally similar between mice and man. However, whether this similarity is based on usage of the same genes is unknown. We show that large-scale gene expression patterns differ substantially between human and mouse B-cell development. Among 644 genes which were differentially expressed in 4 early stages of human B-cell development, only 48, 86, and 75 genes could be identified, which are upregulated in both human and mouse pre–BI, large pre–BII, and small pre–BII cells, respectively. A comparison of mouse B- and T-cell development reveals that gene expression patterns of early murine B- and T-cell precursors are most similar, whereas in more differentiated precursors, human and mouse B cells have a more similar gene expression profile. We conclude that large-scale differences in gene expression patterns between human and mouse B-cell precursors may stem from either selective neutrality or compensatory evolution, whereas the few similarities may stem from negative selection. Gene expression patterns are shaped by ontogenic relationships in early and by functional specialization in later stages of development.
Exploring Treatment Strategies for Type 2 Diabetes
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2007)

Perspectives on the News commentaries are now part of a new, free monthly CME activity. The Mount Sinai School of Medicine, New York, New York, is designating this activity for 2.0 AMA PRA Category 1 credits. If you wish to participate, review this article and visit www.diabetes.procampus.net to complete a posttest and receive a certificate. The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians .

This is the second in a series of articles based on presentations at the American Diabetes Association's 67th Scientific Sessions in June 2007, in Chicago, discussing approaches to the treatment of type 2 diabetes, contrasting the use of older therapies with the use of new agents to lower blood glucose levels.

At a symposium on the use of insulin in treatment of type 2 diabetes, Rury Holman (Oxford, U.K.) reviewed the findings of the UK Prospective Diabetes Study (UKPDS) and A Diabetes Outcome Progression Trial (ADOPT) in terms of the performance of metformin, sulfonylureas, thiazolidinediones, and insulin.

Among the newly diagnosed diabetic individuals entering the UKPDS, mean A1C fell from 9 to 7% with diet modification. At 1 year, mean A1C was 6% with insulin, sulfonylurea, and metformin treatment. After 3, 6, and 9 years in UKPDS, however, only ∼40, 40, and 30% of individuals receiving insulin maintained A1C <7%. Among those on sulfonylurea monotherapy, 45% had A1C <7% at 3 years, but the proportions decreased to 30 and 20% at 6 and 9 years, respectively, with 45, 35, and 15% of those receiving metformin monotherapy maintaining A1C <7% at these times. Holman characterized this inexorable increase as one of the principal challenges of glycemic treatment of individuals with type 2 diabetes. Interestingly, the widely used sulfonylurea glyburide was less …
Radiological Imaging of the Small Intestine: Edited by N C Gourtsoyiannis. Berlin: Springer, 2002, pound214.0, pp 477. ISBN 3-540-65520-4
Authors: A H Freeman
Journal: Gut (2003)

Springer Verlag are producing an extensive range of books entitled Medical Radiology under the general editorship of Professor AL Baert, and this volume on the small intestine is the latest in the line. Professor NC Gourtsoyiannis is its distinguished editor. This is now a very well established series with topics which vary from organ based (that is, pancreas) to technique based (that is, spiral computed tomograpy (CT)) of the abdomen. As with all Springer publications, the illustrations are outstanding and the more than 800 in this book are no exception.

Imaging of the small intestine remains the last redoubt for the gastrointestinal radiologist due to the remorseless advance of endoscopy from both ends of the alimentary tract; a point noted in the foreword by Professor Baert. Virtual colonoscopy has rekindled …
Contrast Volume During Primary Percutaneous Coronary Intervention and Subsequent Contrast-Induced Nephropathy and Mortality
Authors: Giancarlo Marenzi, Emilio Assanelli, Jeness Campodonico, Gianfranco Lauri, Ivana Marana, Monica De Metrio, Marco Moltrasio, Marco Grazi, Mara Rubino, Fabrizio Veglia, Franco Fabbiocchi, Antonio L Bartorelli
Journal: Annals of Internal Medicine (2009)

Background: Contrast-induced nephropathy (CIN) frequently occurs in patients with acute ST-segment elevation myocardial infarction (STEMI) who are undergoing primary percutaneous coronary intervention, and CIN is associated with a more complicated clinical course and increased mortality. Objective: To investigate the association between absolute and weight- and creatinine-adjusted contrast volume, CIN incidence, and clinical outcome in the era of mechanical reperfusion of STEMI. Design: Prospective, observational study. Setting: A university cardiology center in Milan, Italy. Patients: 561 consecutive patients with STEMI who were undergoing primary percutaneous coronary intervention. Measurements: For each patient, the maximum contrast dose was calculated, according to the formula (5 × body weight [kg])/serum creatinine, and the contrast ratio, defined as the ratio between the contrast volume administered and the maximum dose calculated, was assessed. An increase in serum creatinine of more than 25% from baseline was defined as CIN. Results: 115 (20.5%) patients developed CIN. In-hospital mortality was higher among patients with CIN than those without CIN (21.4% vs. 0.9%; P < 0.001). The maximum contrast dose was exceeded in 130 (23%) patients. Patients who received more than the maximum contrast dose (contrast ratio >1) had a more complicated in-hospital clinical course and higher mortality rate (13% vs. 2.8%; P < 0.001) than did patients with a contrast ratio less than 1. Development of CIN was associated with both contrast volume and contrast ratio. Limitation: The association between contrast volume and outcomes was observed in a single center and could be due to comorbid conditions, disease severity, or an unknown factor. Conclusion: During primary percutaneous coronary intervention for STEMI, higher contrast volume is associated with higher rates of CIN and mortality; however, further study is needed to determine whether limiting contrast volume would improve patient outcome. Funding: Centro Cardiologico Monzino, Institute of Cardiology, University of Milan.
Production of acute bronchiolitis in guinea-pigs by human respiratory syncytial virus
Authors: RG Hegele, PJ Robinson, S Gonzalez, JC Hogg
Journal: European Respiratory Journal (1993)

Respiratory syncytial virus (RSV) is the most important cause of acute bronchiolitis in young children, and is implicated in the pathogenesis of paediatric asthma. The present studies were designed to develop a model of acute RSV bronchiolitis in young guinea-pigs, that could be used to study the mechanisms of the acute bronchiolitis and its sequelae. Anaesthetized, one month old guinea-pigs received either 4 x 10(3) plaque forming units of Long strain human RSV or uninfected cell culture medium intranasally. Bronchiolar inflammation was assessed 6 days (n = 10 RSV-inoculated; n = 10 controls) and 14 days (n = 10 RSV-inoculated; n = 9 controls) postinoculation using a semiquantitative histological scoring system. Viral replication within the lung was evaluated by culture, and the intrapulmonary distribution of viral antigens was evaluated by immunohistochemistry. The RSV-inoculated group showed histological evidence of acute bronchiolitis 6 days after inoculation, which subsided by Day 14. Replicating virus was cultured from the lungs of 9 out of 10 RSV-inoculated animals on Day 6, and 2 out of 10 animals on Day 14, with no growth from control animals. Viral antigens were identified primarily within airway epithelial cells on Day 6, and within alveolar macrophages on Day 14. Intranasal inoculation of human RSV into guinea-pigs provides a model of acute RSV bronchiolitis that may facilitate the study of both the pathogenesis of acute infection and the possible role of RSV in the subsequent development of nonspecific bronchial hyperresponsiveness in children.
Discovering Clinical Biomarkers of Ionizing Radiation Exposure with Serum Proteomic Analysis
Authors: Cynthia Ménard, Donald Johann, Mark Lowenthal, Thierry Muanza, Mary Sproull, Sally Ross, James Gulley, Emanuel Petricoin, C. Norman Coleman, Gordon Whiteley, Lance Liotta, Kevin Camphausen
Journal: Cancer Research (2006)

Abstract In this study, we sought to explore the merit of proteomic profiling strategies in patients with cancer before and during radiotherapy in an effort to discover clinical biomarkers of radiation exposure. Patients with a diagnosis of cancer provided informed consent for enrollment on a study permitting the collection of serum immediately before and during a course of radiation therapy. High-resolution surface-enhanced laser desorption and ionization-time of flight (SELDI-TOF) mass spectrometry (MS) was used to generate high-throughput proteomic profiles of unfractionated serum samples using an immobilized metal ion-affinity chromatography nickel-affinity chip surface. Resultant proteomic profiles were analyzed for unique biomarker signatures using supervised classification techniques. MS-based protein identification was then done on pooled sera in an effort to begin to identify specific protein fragments that are altered with radiation exposure. Sixty-eight patients with a wide range of diagnoses and radiation treatment plans provided serum samples both before and during ionizing radiation exposure. Computer-based analyses of the SELDI protein spectra could distinguish unexposed from radiation-exposed patient samples with 91% to 100% sensitivity and 97% to 100% specificity using various classifier models. The method also showed an ability to distinguish high from low dose-volume levels of exposure with a sensitivity of 83% to 100% and specificity of 91% to 100%. Using direct identity techniques of albumin-bound peptides, known to underpin the SELDI-TOF fingerprints, 23 protein fragments/peptides were uniquely detected in the radiation exposure group, including an interleukin-6 precursor protein. The composition of proteins in serum seems to change with ionizing radiation exposure. Proteomic analysis for the discovery of clinical biomarkers of radiation exposure warrants further study. (Cancer Res 2006; 66(3): 1844-50)
Severe Acute Respiratory Syndrome in Dialysis Patients
Authors: Bonnie Ching-Ha Kwan, Chi-Bon Leung, Cheuk-Chun Szeto, Vincent Wai-Sun Wong, Yuk-Lun Cheng, Alex Wai-Yin Yu, Philip Kam-Tao Li
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Reviewed are the clinical features and outcome of 12 chronic dialysis patients (six men) who contracted severe acute respiratory syndrome (SARS) compared with 23 sex- and age-matched nonuremic SARS patients as controls. Eight were on peritoneal dialysis (PD) and four on hemodialysis. Mean age was 58 ± 12 yr for the dialysis patients, and 57 ± 12 yr for the controls. The presenting symptoms of dialysis patients were similar to the controls. With appropriate protection measures, hemodialysis was performed in a dedicated area of the SARS isolation ward, while PD was continued as intermittent PD. In all seven patients with PD effluent tested, SARS-related coronavirus (CoV) could not be identified by polymerase chain reaction (PCR) or viral culture. Three dialysis patients had persistent positive stool PCR after 5 wk, whereas all nondialysis patients had negative stool PCR after 1 wk. Despite dosage adjustment, ribavirin-induced hemolytic anemia was more severe in the dialysis patients. Dialysis patients required longer hospitalization than the controls, but the mortality was similar. With appropriate protective measures, dialysis could be safely performed. Dialysis patients with SARS often require prolonged hospitalization. Furthermore, these patients may have an extended period of viral shedding, which should be carefully monitored for the purpose of infection control.
Parental guilt and respite care
Authors: D Y Moore
Journal: BMJ (1994)

The impact of a handicapped child on a family is immense. As parents of a child with severe learning disability, my wife and I have gone through all the usual stages of bereavement reaction - shock, disbelief, anger, and gradual acceptance. Outsiders sometimes seem to think that our lives have been enriched by Tom, our 7 year old son with the fragile X syndrome. I don't know about enriched; the courses of our lives have been altered, and we have perhaps become more sympathetic to the plight of others, but I could think of many more pleasurable ways of having my life enriched.

* “I could think of many more pleasurable ways of having my life enriched.”

Tom at first glance is an ordinary looking boy. If it were not for his large ears I think that he would pass for normal. It is only in his behaviour that he is obviously different from the rest. His hyperactivity, while usually just keeping us on our toes, can sometimes be heart stopping, especially when he shoots out of the house, …
Adenosine deaminase attenuates canine coronary vasodilatation during regional non-ischaemic myocardial hypoxia
Authors: G. F MERRILL, H F. DOWNEY, S YONEKURA, N WATANABE, C. E JONES
Journal: Cardiovascular Research (1988)

To test the hypothesis that adenosine contributes to the coronary hyperaemia produced by regional non-ischaemic myocardial hypoxia coronary blood flow and myocardial oxygen extraction and consumption were continuously monitored in 21 anaesthetised open chest dogs under the following conditions: control 1--postinstrumentation, steady state control; hypoxia 1--3-5 min of regional (LAD) hypoxaemia (partial pressure of oxygen, PO2, 21.4(2.0) mmHg (3.1(0.2) kPa), coronary arterial oxygen content, CaO2, 3.9(0.4) ml.100 ml-1 (39(4) ml.litre-1): control 2--repeat steady state control; and hypoxia 2--3-5 min repeat regional hypoxaemia (PO2 18.9(2.4) mmHg (2.5(0.3) kPa); CaO2 3.6(0.6) ml.100 ml-1 (36(6) ml.litre-1) blood). Left anterior descending artery perfusion pressure was held constant for all conditions. Control 2 and hypoxia 2 were performed in the presence of locally infused adenosine deaminase (n = 16) or saline vehicle (n = 5). The 16 dogs given adenosine deaminase were further subdivided into those perfused with blood deoxygenated by a donor canine lung (group 1, n = 11) and those perfused with blood from a paediatric oxygenator (group 2, n = 5). Systemic haemodynamics, heart rate, and coronary arterial PO2 and O2 contents were similar during the two control periods and during the two exposures to hypoxia in all three groups. Left anterior descending artery blood flow increased by approximately 400% (p less than 0.05) in all three groups during the first exposure to hypoxia. Myocardial oxygen consumption was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
The autopsy: lessons from the National Confidential Enquiry into Perioperative Deaths
Authors: N. J Carr, M. M E Burke, C. M Corbishley, V. Suarez, K. P McCarthy
Journal: Journal of the Royal Society of Medicine (2002)

Not long ago, the place of the autopsy in medical practice seemed to be primarily the concern of the medical profession. Then the issue of organ retention came to public attention in the UK following the Bristol Royal Infirmary and Alder Hey Inquiries1,2, and the whole question of keeping organs and other samples from autopsies suddenly became the focus of intense media attention, generally negative, in which the British government was involved3,4. In consequence, there is debate about the future role of the autopsy.

Several government-sponsored reviews of the conduct of the medical profession in regard to autopsies have been proposed. Some of these are currently out to consultation and include national standardized autopsy consent forms, a code of practice for bereavement services4, a review of the removal and retention of human organs (including a code of practice for museums, archives and collections of human organs and tissue)5 and a Home Office-led review of death certification and the coronial system in England and Wales6. A comprehensive review of the Human Tissue Act (1961) is planned. These measures will undoubtedly regulate all aspects of autopsy practice and its contribution to research, education and audit. The National Confidential Enquiry into Perioperative Deaths (NCEPOD) stands to be much affected by such changes but must continue to play a part in informing the debate.
Is rheumatoid arthritis in Indians associated with HLA antigens sharing a DR beta 1 epitope?
Authors: W E Ollier, C Stephens, J Awad, D Carthy, A Gupta, D Perry, A Jawad, H Festenstein
Journal: Annals of the Rheumatic Diseases (1991)

HLA class II antigens were identified in a group of 44 patients with rheumatoid arthritis (RA) originating largely from the north or northeast of the Indian subcontinent and resident now in east London. Compared with 67 locally typed east London Asian controls, the prevalence of three HLA-DR antigens was raised in the patients: DR1 18.2% v 6.0% chi 2 = 3.99, DR4 20.5% v 11.9% chi 2 = 1.48, and DRw10 27.3% v 8.9% chi 2 = 6.56. These differences were also found when the patients with RA were compared with a larger control group of 110 northern Indians: DR1 18.2% v 7.2% chi 2 = 4.02, DR4 20.5% v 7.2% chi 2 = 5.56, and DRw10 27.3% v 8.1% chi 2 = 9.7. Twenty five (57%) of the patients expressed at least one of these antigens. All patients were also characterised for HLA-Dw types by mixed lymphocyte culture typing. The prevalence of the HLA-DR4 associated Dw types in the patients was: Dw4 2.3%, Dw10 0%, Dw14 11.4%, and Dw15 6.8%. The DR beta 1 chains of DR1 and DRw10 together with the Dw types of DR4 other than Dw10 share amino acid residues in a region of the third hypervariable region considered to be critical in antigen presentation. It is concluded that RA in Indians is associated with these HLA antigens, and data from this study support the hypothesis of a cross reactive epitope common to HLA specificities associated with RA.