tbuckley/cabot-search huggingface dataset:
RETRACTED ARTICLE: Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: Regulation of MMP 9 by PDEF
Authors: Thomas R Johnson, Sweaty Koul, Binod Kumar, Lakshmipathi Khandrika, Sarah Venezia, Paul D Maroni, Randall B Meacham, Hari K Koul
Journal: Molecular Cancer (2010)

Prostate-derived Ets factor (PDEF) is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF) in prostate cancer.We observed decreased PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immuno-histochemical methods. Reintroduction of PDEF profoundly affected cell behavior leading to less invasive phenotypes in three dimensional cultures. In addition, PDEF expressing cells had altered cell morphology, decreased FAK phosphorylation and decreased colony formation, cell migration, and cellular invasiveness. In contrast PDEF knockdown resulted in increased migration and invasion as well as clonogenic activity. Our results also demonstrated that PDEF downregulated MMP9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate decreased PDEF expression and increased MMP9 expression during the transition to aggressive prostate cancer.These studies demonstrate for the first time negative regulation of MMP9 expression by PDEF, and that PDEF expression was lost in aggressive prostate cancer and was inversely associated with MMP9 expression in clinical samples of prostate cancer. Based on these exciting results, we propose that loss of PDEF along with increased MMP9 expression should serve as novel markers for early detection of aggressive prostate cancer.
Class I chitinases, the panallergens responsible for the latex-fruit syndrome, are induced by ethylene treatment and inactivated by heating
Authors: Rosa Sánchez-Monge, Carlos Blanco, Araceli Díaz Perales, Carmen Collada, Teresa Carrillo, Cipriano Aragoncillo, Gabriel Salcedo
Journal: Journal of Allergy and Clinical Immunology (2000)
LUNG INFLAMMATION: Normal Host Defense or a Complication of Some Diseases?
Authors: H Y Reynolds
Journal: Annual Review of Medicine (1987)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
The clinical relevance of sensitization to pollen‐related fruits and vegetables in unselected pollen‐sensitized adults
Authors: M. Osterballe, T. K. Hansen, C. G. Mortz, C. Bindslev‐Jensen
Journal: Allergy (2005)

Background: Previous studies have described cross‐reactivity between fresh fruits, vegetables and pollen. However, no data demonstrates the clinical relevance of sensitization to pollen‐related fruits and vegetables in unselected pollen‐sensitized adults with and without symptoms in the pollen season. Objective: The aim of this study was to estimate the clinical relevance of sensitization to pollen‐related fruits and vegetables in unselected pollen‐sensitized adults and to examine the diagnostic value of skin‐prick test (SPT), histamine release and specific IgE compared with the outcome of oral challenge. Methods: In total, 936 unselected adults (female : male 479 : 457, median age 33.7 years) were examined for pollen sensitization and clinical cross‐reactivity with pollen‐related fruits and vegetables by questionnaire, SPT, histamine release, specific IgE and oral challenge. Results: The prevalence of pollen sensitization was 23.8% ( n = 223). The probability of a clinical reaction to pollen‐related foods in the respective pollen‐sensitized groups was: 24% (birch), 4% (grass), 10% (mugwort), 35% (birch + grass), 8% (grass + mugwort) and 52% (birch + grass + mugwort). The odds ratio of a clinical reaction to pollen‐related fruits and vegetables in symptomatic pollen‐sensitized adults was as high as four times (birch + grass) the odds ratio of a clinical reaction in asymptomatic pollen‐sensitized adults. Conclusion: This study not only demonstrates a high prevalence of clinical reactions to fruits and vegetables in pollen‐sensitized adults, but also a discrepancy between the prevalence of sensitization to fruits and vegetables and the clinical relevance in different pollen‐sensitized groups with symptoms in the pollen season as a significant factor.
Postoperative Deep Vein Thrombosis in Sudanese Patients
Authors: M. A. Hassan, E. A. Rahman, I. A. Rahman
Journal: BMJ (1973)

The incidence of postoperative deep vein thrombosis diagnosed by radioisotope scanning in 100 Sudanese patients aged 40 or over was 12%. This compares with an incidence of nearly 30% in 542 patients reported from British hospitals using the same diagnostic technique. The reason for the difference is obscure and needs further investigation.
Beauty and the dole.
Authors: R Smith
Journal: BMJ (1986)

Many of Britain's hospitals are ugly and depressing, and more than three million people are unemployed. Wouldn't it make sense if some of the unemployed helped beautify our hospitals? It would, and a walk down the several hundred yards of corridor of Bethnal Green Hospital shows that it is already happening. The corridor is lined with paintings by unemployed people. The first one you see shows a boy fishing in one of the East End's hidden canals. It must be five feet by four, and a casual observer could be excused for thinking it a particularly vibrant and large colour photograph. In fact it is a painting, which might be described as ultrarealist, painted by an unemployed girl who had never painted before. If you were one of the old people who are now the inhabitants of the hospital, you might be reminded of when you were a child and fished in the canal. Or perhaps you would think of your grandson, fishing there at that moment. As you walked on down the corridor you would be reminded of much more, particularly if you knew the East End well. Tubby Isaacs is selling shellfish; bells are being cast
Enhancement of IgE-mediated histamine release from human basophils by viruses: role of interferon.
Authors: S Ida, J J Hooks, R P Siraganian, A L Notkins
Journal: The Journal of Experimental Medicine (1977)

Human leukocytes maintained in culture are induced to release histamine when exposed to ragweed antigen E or anti-IgE. Leukocyte cultures incubated with virus (i.e. HSV-1, Influenza A, and Adeno-1) but not exposed to ragweed antigen E or anti-IgE fail to release histamine. If, however, leukocyte cultures are first exposed to virus and then to ragweed antigen E or anti-IgE, significant enhancement of histamine release occurs. Both infectious and inactivated virus enhance histamine release and the degree of enhancement is related to the concentration of virus and the length of the incubation. Tissue culture fluid harvested 8 h after exposure of leukocytes to virus contains a soluble factor which is capable of enhancing histamine release when added to fresh leukocyte cultures. This factor has all the properties of interferon including species specificity and cannot be dissociated from the antiviral activity of interferon. Moreover, both known inducers of interferon (poly I:poly C) and standard preparations of interferon are capable of enhancing histamine release. The enhancement of histamine release by interferon represents a new biological role for interferon.
Single-Cell Transcription Site Activation Predicts Chemotherapy Response in Human Colorectal Tumors
Authors: Rossanna C. Pezo, Saumil J. Gandhi, L. Andrew Shirley, Richard G. Pestell, Leonard H. Augenlicht, Robert H. Singer
Journal: Cancer Research (2008)

Abstract Candidate gene and pathway approaches, and unbiased gene expression profiling, have identified marker signatures predictive of tumor phenotypes, such as drug sensitivity and invasive or metastatic potential. However, application of such information to evaluation of tumors in the clinic is limited by cell heterogeneity in the tumor. We have developed a novel method of fluorescence in situ hybridization (FISH) that can detect transcriptional activation of individual genes at their site in single cells in the interphase nucleus. A major obstacle in the treatment of colorectal cancer is relative insensitivity to the chemotherapeutic agent 5-Fluorouracil (5-FU). Here, we have developed a sensitive approach to predict relative sensitivity of colorectal cancer cells to 5-FU, using FISH with probes targeted to nascent mRNAs to measure the number of individual cells with active transcription sites for a panel of candidate genes. These results reveal that the transcriptional status of four key genes, thymidylate synthase (TYMS), MORF-related gene X (MRGX), Bcl2-antagonist/killer (BAK), and ATPase, Cu2+ transporting β polypeptide (ATP7B), can accurately predict response to 5-FU. As proof of principle, we show that this transcriptional profile is predictive of response to 5-FU in a small number of patient colon tumor tissues. This approach provides a novel ability to identify and characterize unique minor cell populations in the tumor that may exhibit relative resistance to chemotherapy. [Cancer Res 2008;68(13):4977–82]
Chromosome Mapping and Phylogenetic Analysis of the Cytosolic Acetyl-CoA Carboxylase Loci in Wheat
Authors: J Faris, A Sirikhachornkit, R Haselkorn, B Gill, P Gornicki
Journal: Molecular Biology and Evolution (2001)

The cytosolic isoform of plant acetyl-CoA carboxylase is a multidomain enzyme involved in the synthesis of very-long-chain fatty acids and in secondary metabolism. Chromosome mapping of wheat identified one locus containing cytosolic acetyl-CoA carboxylase genes (Acc-2) and a related partially processed pseudogene (Ψ-Acc-2) in the distal region of the long arm of wheat homoeologous group 3 chromosomes. Multiple copies of the Acc-2 genes, whose presence was suggested by sequence analysis, are likely to be arranged in tandem repeats. At least three out of five genes cloned from hexaploid wheat map to this locus. Another locus containing Acc-2–related sequences is present in the distal region of the long arm of chromosome 5D. The identity of the hybridizing DNA present at this locus remains unknown. A system based on PCR-cloning and DNA sequence analysis of acetyl-CoA carboxylase genes was developed to address various phylogenetic and systematics questions in grasses. It was applied to reconstruct the phylogeny of the Acc-2 genes from D- and S-genome Aegilops and A-genome Triticum diploid species, AABB- and AAGG-genome tetraploid wheat, and AABBDD-genome hexaploid wheat, as well as from rye and barley. The combined cytogenetic and molecular evolution approach allowed assignment of gene sequences included in phylogenetic analysis to specific loci on homoeologous chromosomes. Recurring gene duplication followed by chromosome translocation and/or possible loss of some gene copies, as well as loss of introns, occurred in the gene family in different plant lineages. Two major Acc-2 clades appeared before the divergence of barley and rye. Nucleotide substitution rates in different parts of the Acc-2 gene were assessed. This analysis of the Acc-2 loci provides detailed information regarding evolutionary events at a low–copy-number locus containing important functional genes. These events are likely to be common and to play a significant role in shaping grass genomes.
CLONAL NATURE OF THE IMMUNE RESPONSE TO PHOSPHORYLCHOLINE
Authors: J. Latham Claflin, Joseph M. Davie
Journal: The Journal of Experimental Medicine (1974)

A new idiotypic determinant(s) on mouse anti-PC antibodies is described. Antibodies to the determinant(s) were raised in rabbits by immunization with HOPC 8, a PC-binding myeloma protein, and were isolated from HOPC 8 immunoadsorbent by elution with PC. These antibodies react with binding site determinants on anti-PC antibodies raised in all 15 inbred mouse strains tested regardless of histocompatibility or allotype, but fail to react with antibodies of other specificities or with anti-PC antibodies raised in other rodent species. These results correlate closely with other studies which show similar binding specificity of anti-PC antibodies raised in 17 different strains of mice. The site-associated idiotypic determinant(s) is clearly distinct from that detected by mouse anti-HOPC 8 antisera. This latter determinant(s) is present on anti-PC antibodies of only a few strains of mice and may not be in the binding site.
Detecting an Overall Survival Benefit that Is Derived From Progression-Free Survival
Authors: Kristine R. Broglio, Donald A. Berry
Journal: JNCI Journal of the National Cancer Institute (2009)

Whether progression-free survival (PFS) or overall survival (OS) is the more appropriate endpoint in clinical trials of metastatic cancer is controversial. In some disease and treatment settings, an improvement in PFS does not result in an improved OS.We partitioned OS into two parts and expressed it as the sum of PFS and survival postprogression (SPP). We simulated randomized clinical trials with two arms that had respective medians for PFS of 6 and 9 months. We assumed no treatment difference in median SPP. We found the probability of a statistically significant benefit in OS for various median SPP and observed P values for PFS. We compared the sample sizes required for PFS vs OS for various median SPP. We compare our results with the literature regarding surrogacy of PFS for OS by use of the correlation between hazard ratios for PFS and OS. All statistical tests were two-sided.For a trial with observed P value for improvement in PFS of .001, there was a greater than 90% probability for statistical significance in OS if median SPP was 2 months but less than 20% if median SPP was 24 months. For a trial requiring 280 patients to detect a 3-month difference in PFS, 350 and 2440 patients, respectively, were required to have the same power for detecting a real difference in OS that is carried over from the 3-month benefit in PFS when the median SPP was 2 and 24 months.Addressing SPP is important in understanding treatment effects. For clinical trials with a PFS benefit, lack of statistical significance in OS does not imply lack of improvement in OS, especially for diseases with long median SPP. Although there may be no treatment effect on SPP, its variability so dilutes the OS comparison that statistical significance is likely lost. OS is a reasonable primary endpoint when median SPP is short but is too high a bar when median SPP is long, such as longer than 12 months.
Mutation of <b> <i>hCDC4</i> </b> Leads to Cell Cycle Deregulation of Cyclin E in Cancer
Authors: Susanna Ekholm Reed, Charles H. Spruck, Olle Sangfelt, Frank van Drogen, Elisabeth Mueller-Holzner, Martin Widschwendter, Anders Zetterberg, Steven I. Reed
Journal: Cancer Research (2004)

hCDC4, the gene that encodes the F-box protein responsible for targeting cyclin E for ubiquitin-mediated proteolysis, has been found to be mutated in a number of primary cancers and cancer-derived cell lines. We have observed that functional inactivation of hCDC4 does not necessarily correlate with elevated levels of cyclin E in tumors. Here we show, however, that hCDC4 mutation in primary tumors correlates strongly with loss of cell cycle regulation of cyclin E. Similarly, a breast carcinoma-derived cell line mutated for hCDC4 exhibits cell cycle deregulation of cyclin E, but periodic expression is restored by reintroducing hCDC4 via retroviral transduction. Conversely, small interfering RNA-mediated silencing of hCdc4 deregulates cyclin E with respect to the cell cycle. These results indicate that hCdc4 function is an absolute prerequisite for cell cycle regulation of cyclin E levels, and loss of hCdc4 function is sufficient to deregulate cyclin E.
2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP–dependent metabolic regulation of chromatin structure
Authors: Mireia Garriga-Canut, Barry Schoenike, Romena Qazi, Karen Bergendahl, Timothy J Daley, Rebecca M Pfender, John F Morrison, Jeffrey Ockuly, Carl Stafstrom, Thomas Sutula, Avtar Roopra
Journal: Nature Neuroscience (2006)
SCHIZOPHRENIC-LIKE MECHANISMS IN MONKEYS
Authors: PETER G. S. BECKETT, C. E. FROHMAN, J. S. GOTTLIEB, J. B. MOWBRAY, R. C. WOLF
Journal: American Journal of Psychiatry (1963)

These preliminary results are of interest in that they relate a biochemical abnormality similar to the one found in schizophrenia to social isolation and an experimental lack of tactile stimulation in early life. It is important to note that in this study the biochemical defect was found not to be correlated closely with disturbed behavior, indicating amongst other things that the complexities of behavior probably have many other antecedents besides biochemical maladaptation. Such antecedents must almost certainly include patterns of behavior learned from whatever models were available in the environment during psychologic maturation. Hopefully in future studies it will be possible to manipulate both these sets of variables with some precision. The interaction of biologic or general somatic factors, and psychologic or learned factors, in the origins of disturbed behavior has always been a central issue for psychiatry. The present study may enable these problems to be approached using primates as an experimental model. From the biologic point of view alone it would probably be very worthwhile to investigate the type, timing and intensity of stimulation necessary to produce the effect discussed in this paper. For instance is stimulation of certain areas of skin, such as the oral or genital areas, especially important? And what about other types of stimulation–proprioceptive, vestibular, visual or auditory? Is it possible that more complex experiences are significant such as the affective components of the perception of objects, or the learning of patterned responses? The scientific manipulation of both biologic and psychologic variables in a monkey colony might give answers to these questions, and to many others still unasked.
Cardiovascular molecular imaging: an overview
Authors: A. Saraste, S. G. Nekolla, M. Schwaiger
Journal: Cardiovascular Research (2009)

Molecular imaging is non-invasive visualization and measurement of biological processes at the molecular and cellular level within a living organism. This review provides a description of the various molecular imaging techniques for imaging cardiovascular targets and their potential clinical implications. Molecular imaging has relied mainly on nuclear imaging, but advances in nanoparticle probe development have made magnetic resonance imaging and ultrasound as emerging, radiation-free alternatives. Targeted imaging of vascular inflammation or thrombosis may allow improved risk assessment of atherosclerosis by detecting plaques at high risk of acute complications. Imaging probes detecting myocardial apoptosis, metabolic alterations, injury to extracellular matrix, angiogenesis, or innervation may provide tools for assessing risk of arrhythmias and left ventricular remodelling associated with progressive cardiac dysfunction and heart failure. Although clinical experience remains limited, careful evaluation of safety as well as validation of diagnostic and prognostic value of these techniques in clinical trials is still needed.
Randomized Trial to Assess the Impact of Venlafaxine and Soy Protein on Hot Flashes and Quality of Life in Men With Prostate Cancer
Authors: Mara Z. Vitolins, Leah Griffin, W. Vic Tomlinson, Jacqueline Vuky, Paul T. Adams, Dawn Moose, Bart Frizzell, Glenn J. Lesser, Michelle Naughton, James E. Radford, Edward G. Shaw
Journal: Journal of Clinical Oncology (2013)

Purpose Hot flashes occur in approximately 80% of androgen-deprived men. Few intervention studies have been conducted to relieve hot flashes in men. Patients and Methods Eligible androgen-deprived men were randomly assigned to one of four daily regimens (2 × 2 factorial design) for 12 weeks: milk protein powder and placebo pill, venlafaxine and milk protein powder, soy protein powder and placebo pill, or venlafaxine and soy protein powder. The primary end point was hot flash symptom severity score (HFSSS), defined as number of hot flashes times severity. The secondary end point was quality of life (QoL), assessed by using the Functional Assessment of Cancer Therapy-Prostate. Results In all, 120 men age 46 to 91 years participated. Most were white (78%) and overweight or obese (83%). Toxicity was minimal. Neither venlafaxine nor soy protein alone or in combination had a significant effect on HFSSS. Soy protein, but not venlafaxine, improved measures of QoL. Conclusion In androgen-deprived men, neither venlafaxine nor soy proved effective in reducing hot flashes. Interventions that appear effective for decreasing hot flashes in women may not always turn out to be effective in men.
A Doctor's Occupation
Authors: A. M O'Donnell
Journal: BMJ (2009)

This poignant memoir gives us a frank and emotive account of life spent in the Channel Islands under German occupation. Lewis arrived in Jersey in 1935 and became a partner in a busy general practice. Towards the outbreak of war many islanders began to leave for the mainland. Lewis was able to leave Jersey on one of the last boats, together with his pregnant wife. His partner had promised to remain to take care of their patients. On reaching his family home in Wales, Lewis received a telephone call to say that, without warning, his partner had panicked and …
Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial
Authors: Roger Stupp, Monika E Hegi, Warren P Mason, Martin J van den Bent, Martin JB Taphoorn, Robert C Janzer, Samuel K Ludwin, Anouk Allgeier, Barbara Fisher, Karl Belanger, Peter Hau, Alba A Brandes, Johanna Gijtenbeek, Christine Marosi, Charles J Vecht, Karima Mokhtari, Pieter Wesseling, Salvador Villa, Elizabeth Eisenhauer, Thierry Gorlia, Michael Weller, Denis Lacombe, J Gregory Cairncross, René-Olivier Mirimanoff
Journal: The Lancet Oncology (2009)