tbuckley/cabot-search huggingface dataset:
EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment
Authors: Yuanjie Hu, Peter Dion Pioli, Eric Siegel, Qinghua Zhang, Jodi Nelson, Abhishek Chaturbedi, Marlon S Mathews, Daniel I Ro, Selma Alkafeef, Nelson Hsu, Mark Hamamura, Liping Yu, Kenneth R Hess, Bruce J Tromberg, Mark E Linskey, Yi-Hong Zhou
Journal: Molecular Cancer (2011)

Abstract Purpose There are conflicting reports regarding the function of EFEMP1 in different cancer types. In this study, we sought to evaluate the role of EFEMP1 in malignant glioma biology. Experimental Design Real-time qRT-PCR was used to quantify EFEMP1 expression in 95 glioblastoma multiforme (GBM). Human high-grade glioma cell lines and primary cultures were engineered to express ectopic EFEMP1, a small hairpin RNA of EFEMP1, or treated with exogenous recombinant EFEMP1 protein. Following treatment, growth was assayed both in vitro and in vivo (subcutaneous (s.c.) and intracranial (i.c.) xenograft model systems). Results Cox regression revealed that EFEMP1 is a favorable prognostic marker for patients with GBM. Over-expression of EFEMP1 eliminated tumor development and suppressed angiogenesis, cell proliferation, and VEGFA expression, while the converse was true with knock-down of endogenous EFEMP1 expression. The EFEMP1 suppression of tumor onset time was nearly restored by ectopic VEGFA expression; however, overall tumor growth rate remained suppressed. This suggested that inhibition of angiogenesis was only partly responsible for EFEMP1's impact on glioma development. In glioma cells that were treated by exogenous EFEMP1 protein or over-expressed endogenous EFEMP1, the EGFR level was reduced and AKT signaling activity attenuated. Mixing of EFEMP1 protein with cells prior to s.c. and i.c. implantations or injection of the protein around the established s.c. xenografts, both significantly suppressed tumorigenicity. Conclusions Overall, our data reveals that EEFEMP1 suppresses glioma growth in vivo , both by modulating the tumor extracellular microenvironment and by altering critical intracellular oncogenic signaling pathways.
Reduction in plasma homocysteine level in patients with rheumatoid arthritis given pulsed glucocorticoid treatment
Authors: P E Lazzerini
Journal: Annals of the Rheumatic Diseases (2003)

High levels of homocysteine are commonly found in patients with rheumatoid arthritis (RA), thus accounting, at least in part, for the high rate of mortality for cardiovascular events in these subjects.1–5 The mechanisms responsible for hyperhomocysteinaemia in RA are not clear. However, drugs such as methotrexate and sulfasalazine affect homocysteine metabolism, interfering with vitamin metabolism and absorption.1,3,5 Furthermore, an increased use or accelerated catabolism of vitamin B6 has been shown in chronic inflammatory diseases, particularly RA.2,6–8

Recently, it has been shown that rats treated with cortisol have plasma homocysteine levels lower than controls.9 Glucocorticoids increase the activity of betaine-homocysteine methyltransferase, which transforms homocysteine in methionine with consumption of betaine as methyl donor coenzyme.10 Moreover, steroids may produce genomic inhibition of several cytokines, …
Isabella Leitch's contributions to the development of systematic reviews of research evidence
Authors: Frank Hytten
Journal: Journal of the Royal Society of Medicine (2010)

Isabella Leitch was born in 1890 in the Aberdeenshire fishing town of Peterhead; her father was the local postmaster. The family must have been reasonably well-off because Isabella and her three sisters were all well-educated at a time when relatively few women reached university. Partly because she had seen Peterhead children having to go barefoot in winter, she grew up with a passionate hostility to social inequality and was an active suffragette. She was apparently sufficiently similar in appearance to Christabel Pankhurst to take her place as a decoy on the stage of the Albert Hall, allowing Miss Pankhurst to escape a riotous situation through a back door. Following her graduation in science from Aberdeen University, Isabella Leitch spent time during World War I studying a variety of haemoglobins in Copenhagen with Professor A Krogh, and it was during that time that her lifelong interest in genetics began. She was even interested in aircraft design, and I remember seeing a collection of slides illustrating various aircraft which she had used for lectures at about that time. Despite being an experienced research worker with a Doctorate of Science awarded by Aberdeen University in 1919, Isabella Leitch was unable to find a research post in Aberdeen. In 1923, however, she found a job as a temporary librarian at the Rowett Research Institute, and this was to provide the foundation for her encyclopaedic knowledge of the field of nutrition, which, in turn, led to her appointment as personal assistant to the director of the Rowett Research Institute, John Boyd Orr. She told me that, when she began working with him, his Calvinist upbringing had led him to believe that the poor were poor because they deserved to be. She changed his mind, and it was her influence that led to Orr’s landmark book Food, Health and Income, and from that, his founding directorship of the UN Food and Agriculture Organization.
A Stochastic Model for Cancer Stem Cell Origin in Metastatic Colon Cancer
Authors: Christine Odoux, Helene Fohrer, Toshitaka Hoppo, Lynda Guzik, Donna Beer Stolz, Dale W. Lewis, Susanne M. Gollin, T. Clark Gamblin, David A. Geller, Eric Lagasse
Journal: Cancer Research (2008)

Abstract Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability. [Cancer Res 2008;68(17):6932–41]
Adjuvant Immunotherapy of Resected, Intermediate-Thickness, Node-Negative Melanoma With an Allogeneic Tumor Vaccine: Impact of HLA Class I Antigen Expression on Outcome
Authors: Jeffrey A. Sosman, Joseph M. Unger, P.-Y. Liu, Lawrence E. Flaherty, Min S. Park, Raymond A. Kempf, John A. Thompson, Paul I. Terasaki, Vernon K. Sondak
Journal: Journal of Clinical Oncology (2002)

An association between expression of > or = two of five HLA class I antigens (HLA-A2, HLA-A28, HLA-B44, HLA-B45, and HLA-C3; collectively called M5) and response to an allogeneic melanoma vaccine (Melacine; Corixa Corporation, Seattle, WA) has been described in stage IV melanoma. This study investigated whether class I antigen expression impacted relapse-free survival (RFS) after adjuvant therapy with this vaccine.We performed class I (HLA-A, HLA-B, and HLA-C) serotyping on patients enrolled onto Southwest Oncology Group Trial 9035, a randomized, observation-controlled, phase III trial of adjuvant Melacine. All patients had clinically node-negative cutaneous melanoma (1.5 to 4.0 mm). Interactions between treatment and class I antigen expression were tested. Analyses involved all serotyped patients and were adjusted for tumor thickness, method of nodal staging, sex, ulceration, and primary tumor site.HLA typing was performed on 553 (80%) of the 689 enrolled patients (294 vaccinated and 259 observed). Expression of > or = two M5 antigens was associated with a superior vaccine treatment effect. Among patients who matched > or = two of the M5, the 97 vaccine-treated patients had improved RFS compared with the 78 observation patients (5-year relapse-free survival, 83% v 59%; P =.0002). The major components of this effect were contributed by HLA-A2 and HLA-C3. Among those who were HLA-A2-positive and/or HLA-C3-positive, the 5-year RFS for vaccinated patients was 77%, compared with 64% for observation (P =.004). There was no impact of HLA-A2 and/or HLA-C3 expression among observation patients.This prospective analysis indicates a highly significant benefit of adjuvant therapy with Melacine among patients expressing > or = two of the M5 class I antigens, validating a prior observation in stage IV disease. HLA-A2 and HLA-C3 contributed most to this effect. Processed melanoma peptides found in Melacine may be presented by HLA-A2 and HLA-C3 and play a role in preventing relapse in vaccinated patients.
Size Matters: Non-LTR Retrotransposable Elements and Ectopic Recombination in Drosophila
Authors: D. A. Petrov
Journal: Molecular Biology and Evolution (2003)

The Drosophila melanogaster genome contains approximately 100 distinct families of transposable elements (TEs). In the euchromatic part of the genome, each family is present in a small number of copies (5–150 copies), with individual copies of TEs often present at very low frequencies in populations. This pattern is likely to reflect a balance between the inflow of TEs by transposition and the removal of TEs by natural selection. The nature of natural selection acting against TEs remains controversial. We provide evidence that selection against chromosome abnormalities caused by ectopic recombination limits the spread of some TEs. We also demonstrate for the first time that some TE families in the Drosophila euchromatin appear to be only marginally affected by purifying selection and contain many copies at high population frequencies. We argue that TEs in these families attain high population frequencies and even reach fixation as a result of low family-wide transposition rates leading to low TE copy numbers and consequently reduced strength of selection acting on individual TE copies. Fixation of TEs in these families should provide an upward pressure on the size of intergenic sequences counterbalancing rapid DNA loss through small deletions. Copy-number–dependent selection on TE families caused by ectopic recombination may also promote diversity among TEs in the Drosophila genome.
Bronchiolitis obliterans organising pneumonia associated with the use of nitrofurantoin
Authors: R J Cameron
Journal: Thorax (2000)

The spectrum of nitrofurantoin lung injury continues to widen. The case histories are presented of two patients who developed lung disease associated with the use of nitrofurantoin with histological features of bronchiolitis obliterans organising pneumonia (BOOP), a rare but recognised form of drug induced injury. The two middle aged women presented with respiratory symptoms after prolonged treatment with nitrofurantoin. Both had impaired lung function and abnormal computed tomographic scans, and their condition improved when nitrofurantoin was withdrawn and corticosteroid treatment commenced. The favourable outcome in these two patients contrasts with the fatal outcome of the two other reported cases of nitrofurantoin induced BOOP. We suggest that the previous classification of nitrofurantoin induced lung injury into "acute" and "chronic" injury is an oversimplification in view of the wide variety of pathological entities that have subsequently emerged.
NMR Spectroscopy of Brain Metabolism In Vivo
Authors: James W. Prichard, Robert G. Shulman
Journal: Annual Review of Neuroscience (1986)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Effects of the Long-Acting Human Glucagon-Like Peptide-1 Analog Liraglutide on β-Cell Function in Normal Living Conditions
Authors: Andrea Mari, Kristine Degn, Birgitte Brock, Joergen Rungby, Ele Ferrannini, Ole Schmitz
Journal: Diabetes Care (2007)

iraglutide is a long-acting glucagonlike peptide (GLP)-1 analog, which exerts its glucose-lowering action through multiple mechanisms (1).One important feature of liraglutide is its ability to enhance ␤-cell function.The effects on ␤-cell function have been demonstrated using standardized ␤-cell function tests based on intravenous glucose administration (2-4).However, these studies may not reflect the modes of action of liraglutide during normal living.To assess the effects of liraglutide on ␤-cell function in normal living, we have used a validated ␤-cell model to analyze 24-h triple-meal experiments. RESEARCH DESIGN ANDMETHODS -This study includes data used for a different analysis in a previous publication (3), where the experimental protocol, approved by the local ethics committee and performed in accordance with the Helsinki Declaration, was described in detail.Thirteen type 2 diabetic patients (five women and eight men) were examined.Their mean Ϯ SD age was 56.4 Ϯ 9.2 years, BMI was 31.2Ϯ 3.6 kg/m 2 , last measured A1C before inclusion was 7.3 Ϯ 0.4% (normal range Ͻ6.4%), and the duration of diabetes was 3.0 Ϯ 2.6 years.The study is a randomized, doubleblind, placebo-controlled, crossover
The non-invasive diagnosis of cirrhosis using the Fibroscan must be performed with cause-specific stiffness cut-offs.
Authors: E Nguyen-Khac, D Capron, A Braillon, J L Dupas
Journal: Gut (2008)

We read the article by Fraquelli et al ( Gut 2007; 56 :968–73) with great interest. In addition to the Fibroscan’s excellent reproducibility, the authors reported stiffness cut-offs for the non-invasive diagnosis of liver fibrosis with, notably, a value of 11.9 kPa for cirrhosis. This choice is arguable because the study population …
Recent Clinicolaboratory Observations in the Treatment of Acute Gonococcal Urethritis in Men
Authors: Gamil Ashamalla
Journal: JAMA (1966)

Diagnosis of acute gonorrhea was made for 350 male inmates who were treated in a controlled clinicolaboratory program using four antibiotic schemata. Low failure rates, 1.8% and 2.1%, respectively, were observed with oxytetracycline therapy and procaine penicillin G, 2.4 million units, administered immediately. Procaine penicillin G in four daily doses of 600,000 units yielded 3.7% failures. Repository penicillin, 2.4 million units, administered immediately, increased treatment failures to 5.9%. Nonspecific urethritis sequelae were markedly diminished with the oxytetracycline regimen. In vitro observations revealed all gonococci strains studied were sensitive to penicillin and oxytetracycline despite occasional in vivo treatment failures. Treatment failure rates indicate the need to resurvey gonorrhea therapy at periodic intervals. Organisms of the tribe Mimeae were not encountered in this study; until substantive evidence is offered this group should be eliminated from further serious consideration in gonorrhea in men.
Childhood cancer and power lines: Authors' reply
Authors: Gerald Draper, Tim Vincent, Mary E Kroll, John Swanson
Journal: BMJ (2005)

Childhood cancer and power linesWhat do the data mean?Editor-Draper et al used distance of mother's home from high voltage overhead transmission lines (predominantly 275 kV and 400 kV) at the time of her child's birth as a proxy for her child's subsequent exposure to power-frequency magnetic fields (reviewed by Ahlbom et al). 1 2 As they acknowledge, this is a crude estimate since, in contrast to other reports, 2 no household measurements were taken, no data on more prevalent low voltage distribution sources were collected, no information from other time points in the child's life was obtained, variations during the 33 years period studied were not considered, and no validatory home visits were carried out.A recent report into residential exposures to magnetic fields in the United Kingdom estimated that proximity to high voltage lines, 275 kV and above, explained only 9% of those with measurements ≥ 0.2 microtesla ( T). 3 National data on the distribution of houses in relation to high voltage lines in the UK were provided (J Swanson, National Grid Transco, personal communication, 2000) to the UK Childhood Cancer Study (UKCCS) Group for its study of power lines and childhood cancer, to assess the representativeness of study subjects. 4 An equivalent comparison using National Grid data spanning the far longer period investigated in the paper by Draper et al was not undertaken.The assessments of distance to power lines in the UKCCS were made for all registered controls, who have been shown to represent the general population. 5plot of the distributions of the leukaemia and non-leukaemia cases and controls in the study by Draper et al, national populations, and UKCCS populations by distance from high voltage lines (figure) seems to show that the leukaemia controls used in the analysis presented by Draper et al are systematically different.Their positive result over 100 m may therefore be explained not by an excess of cases but by a deficit of controls in the early years of the study.
Mutations of the Hereditary Hemochromatosis Candidate Gene<i>HLA-H</i>in Porphyria Cutanea Tarda
Authors: Manuela Santos, Hans C. Clevers, Joannes J.M. Marx
Journal: New England Journal of Medicine (1997)

To the Editor: Porphyria cutanea tarda is characterized by reduced activity of uroporphyrinogen decarboxylase, with hepatic accumulation of uroporphyrins, and photosensitive skin lesions. The clini...
Diazepam and Paraldehyde for Treatment of Severe Delirium Tremens
Authors: W. L. Thompson, A. D. Johnson, Willis C Maddrey
Journal: Annals of Internal Medicine (1975)

Thirty-four patients with severe delirium tremens were allocated randomly to treatment with paraldehyde (10 ml rectally every 30 minutes) or diazepam (10 mg then 5 mg intravenously every 5 minutes) until they were calm but awake. Diazepam-treated patients became calm in one half the time needed to calm patients with paraldehyde. Half of the patients had delirium tremens in association with pneumonia, pancreatitis, or alcoholic hepatitis; these patients required twice as much paraldehyde or diazepam for initial calming as patients with delirium tremens alone. Maintenance of a calm state was accomplished easily with either diazepam, intramuscularly, or paraldehyde, rectally. Adverse reactions occurred in nine patients, all of whom had been treated with paraldehyde; these patients had greater degrees of fever, tachypnea, and tachycardia and required three times longer for initial calming than patients without adverse reactions. Diazepam given under this regimen is a safe and effective sedative for management of combative patients with severe delirium tremens.
Inverse correlation of serum paraoxonase and homocysteine thiolactonase activities and antioxidant capacity of high-density lipoprotein with the severity of cardiovascular disease in persons with type 2 diabetes mellitus
Authors: M. Raj Lakshman, Chandra S. Gottipati, Shivani J. Narasimhan, Jennifer Munoz, Philippe Marmillot, Eric S. Nylen
Journal: Metabolism (2006)
Parental Cultural Attitudes and Beliefs Regarding Young Children and Television
Authors: Wanjiku F. M. Njoroge, Laura M. Elenbaas, Michelle M. Garrison, Mon Myaing, Dimitri A. Christakis
Journal: JAMA Pediatrics (2013)

Research has shown that preschool-aged children spend considerable time with media, and risks and benefits for cognitive and behavioral outcomes exist depending on what is watched and how it is watched.To examine the associations among child race/ethnicity, parental beliefs/attitudes about television (TV) and child development, and TV viewing habits of young children, and to assess reasons for existing racial/ethnic disparities in children's media use.Parents completed demographic questionnaires, reported on attitudes regarding media's risks and benefits to their children, and completed 1-week media diaries where they recorded all of the programs their children watched. Enrollment was from March 13, 2009, to April 12, 2010. The study was conducted at 2 metropolitan Seattle pediatric clinics and an academic practice network, each serving a diverse population of patients, and involved a community-based sample of 596 parents of children aged 3 to 5 years.Parental beliefs/attitudes regarding screen time and TV viewing habits of young children.Overall, children watched an average (SD) of 462.0 (315.5) minutes of TV per week. African American children watched more TV per week than non-Hispanic white children (mean [SD], 638.0 [450.9] vs 431.0 [282.6] minutes; P < .01); however, these differences were no longer statistically significant after controlling for attitudes and demographic covariates (eg, family socioeconomic status). It is important to note that socioeconomic status confounded the results for race/ethnicity, and the association between race/ethnicity and media time across the sample was no longer statistically significant after adjusting for family socioeconomic status. However, significant differences were found between parents of ethnically/racially diverse children and parents of non-Hispanic white children regarding the perceived positive effects of TV viewing, even when parental education and family income were taken into account.Differences in parental beliefs/attitudes regarding the effects of media on early childhood development may help explain growing racial/ethnic disparities in child media viewing/habits, but more research is needed to understand the cultural nuances of the observed differences.
Calcium channel blockers. Lessons learned from MIDAS and other clinical trials
Authors: A. V. Chobanian
Journal: JAMA (1996)

Calcium channel blocking drugs have held great promise for the treatment of a variety of cardiovascular diseases, including angina pectoris, systemic and pulmonary hypertension, certain cardiac arrhythmias, and Raynaud's disease. Their popularity has increased considerably over the past decade and at present, calcium channel blockers are prescribed as frequently for hypertension as are diuretics and angiotensinconverting enzyme (ACE) inhibitors and more than β-blockers. 1 However, although calcium channel blockers represent an important part of the therapeutic armamentarium against cardiovascular diseases, concerns have been raised about these drugs, particularly the short-acting dihydropyridine derivatives. The results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) reported in this issue of The Journal 2 add to these concerns.  See also p 785.  MIDAS was a large, randomized, double-blind, and expensive clinical trial that compared the effects of isradipine, a short-acting dihydropyridine, and hydrochlorothiazide on the course of carotid artery disease in hypertensive patients. The
Barriers to a Career Focus in Cancer Prevention: A Report and Initial Recommendations From the American Society of Clinical Oncology Cancer Prevention Workforce Pipeline Work Group
Authors: Carol J. Fabian, Frank L. Meyskens, Dean F. Bajorin, Thomas J. George, Joanne M. Jeter, Shakila Khan, Courtney A. Tyne, William N. William
Journal: Journal of Clinical Oncology (2015)

To assist in determining barriers to an oncology career incorporating cancer prevention, the American Society of Clinical Oncology (ASCO) Cancer Prevention Workforce Pipeline Work Group sponsored surveys of training program directors and oncology fellows.