tbuckley/cabot-search huggingface dataset:
In vivo analysis of the role of aberrant histone deacetylase recruitment and RARα blockade in the pathogenesis of acute promyelocytic leukemia
Authors: Hiromichi Matsushita, Pier Paolo Scaglioni, Mantu Bhaumik, Eduardo M. Rego, Lu Fan Cai, Samia M. Majid, Hayato Miyachi, Akira Kakizuka, Wilson H. Miller, Pier Paolo Pandolfi
Journal: The Journal of Experimental Medicine (2006)

The promyelocytic leukemia–retinoic acid receptor α (PML-RARα) protein of acute promyelocytic leukemia (APL) is oncogenic in vivo. It has been hypothesized that the ability of PML-RARα to inhibit RARα function through PML-dependent aberrant recruitment of histone deacetylases (HDACs) and chromatin remodeling is the key initiating event for leukemogenesis. To elucidate the role of HDAC in this process, we have generated HDAC1–RARα fusion proteins and tested their activity and oncogenicity in vitro and in vivo in transgenic mice (TM). In parallel, we studied the in vivo leukemogenic potential of dominant negative (DN) and truncated RARα mutants, as well as that of PML-RARα mutants that are insensitive to retinoic acid. Surprisingly, although HDAC1-RARα did act as a bona fide DN RARα mutant in cellular in vitro and in cell culture, this fusion protein, as well as other DN RARα mutants, did not cause a block in myeloid differentiation in vivo in TM and were not leukemogenic. Comparative analysis of these TM and of TM/PML−/− and p53−/− compound mutants lends support to a model by which the RARα and PML blockade is necessary, but not sufficient, for leukemogenesis and the PML domain of the fusion protein provides unique functions that are required for leukemia initiation.
Obstructive sleep apnea in Georgia family: Is it hereditary?
Authors: John Elliott
Journal: JAMA (1978)

A new study of obstructive sleep apnea in three adult male members of a single Georgia family adds to the growing evidence that the syndrome is controlled by a hereditary factor. The study, undertaken at the Gainesville (Fla) Veterans Administration Hospital, revealed episodic apnea, hypoventilation, and oxygen desaturation in one patient displaying classic sleep apnea as well as in his 9-year-old son and 32-year-old brother. Another brother of the index patient could not be studied, since he could not fall asleep during attempted polysomnography. Three daughters of the index patient were unavailable for evaluation. "Although we cannot prove a hereditary relationship in all instances of sleep apnea," said Robert A. Rostand, MD, formerly of the Department of Pulmonary Medicine at the Gainesville VA Hospital, "the case of this one family, where obesity, excessive snoring as well as altered neural control mechanisms have all been identified, strongly suggests a hereditary factor
Is perception of 3-D surface configurations cognitively penetrable?
Authors: Thomas V. Papathomas
Journal: Behavioral and Brain Sciences (1999)

Among Pylyshyn's most important questions is determining the boundaries of early vision. A simple stimulus illustrates that, in addition to the dominant percept, most observers can perceive alternative interpretations of 3-D surface layout only after provided with suggestions. These observations may indicate that cognitive influences reach the stages of visual processing where 3-D surface configurations are resolved.
Birth Cohort and Calendar Period Trends in Breast Cancer Mortality in the United States and Canada
Authors: R. E. Tarone, K. C. Chu, L. A. Gaudette
Journal: JNCI Journal of the National Cancer Institute (1997)

Previous studies of regional and temporal variation in U.S. breast cancer mortality rates have been confined largely to analyses of rates for white women.Breast cancer mortality rates from 1969 through 1992 for white women and black women in four regions of the United States and for all women throughout Canada were compared to identify racial, regional, and temporal differences. Differences and trends in the rates were evaluated in view of breast cancer risk factors and relevant medical interventions.Age-period-cohort models were fit to the data, and changes in birth cohort trends (suggesting a change in a breast cancer risk factor or protective factor) and calendar period trends (suggesting, in part, the impact of new or improved medical interventions) were examined.Breast cancer mortality rates for white women were significantly higher in the Northeast than in any other region of the United States (two-sided t tests; P<.005); the rates for black women were not. Birth cohort trends for all women were similar until about 1940, with a moderation of mortality risk beginning around 1924. A marked moderation of risk by 4-year birth cohorts was observed for U.S. white women born after 1950, whereas stable or slightly decreasing trends were observed for U.S. black women and Canadian women. For women born from 1924 to around 1938, fertility rates increased for all three groups; after 1950, they declined uniformly. Looking at temporal effects, we found that the slope of the mortality calendar period trend increased in the 1980s compared with the 1970s for all women. In the last calendar period, 1991-1992, a trend of decreasing mortality rates was found for white women in the United States and for Canadian women.Widespread environmental exposures are unlikely to explain the higher relative breast cancer mortality rates observed for U.S. white women in the Northeast, since the rates for black women in this region were not higher than in other regions. The moderation of breast cancer mortality rates for women born between 1924 and 1938 coincides with increased fertility rates following World War II. Stable or decreasing mortality rates for U.S. women and Canadian women born after 1950 were not expected in view of declining fertility rates, suggesting a change in a breast cancer risk factor or protective factor. The increase in calendar period trend slope in the 1980s likely reflects the coincident rise in breast cancer diagnosis via mammography. The recent decline in calendar period trend for white women in the United States and for Canadian women may be the result of earlier detection and increased use of adjuvant therapy.
High-throughput analysis of chromosome translocations and other genome rearrangements in epithelial cancers
Authors: Scott Newman, Paul AW Edwards
Journal: Genome Medicine (2010)

Genes that are broken or fused by structural changes to the genome are an important class of mutation in the leukemias and sarcomas but have been largely overlooked in the common epithelial cancers. Large-scale sequencing is changing our perceptions of the cancer genome, and it is now being applied to structural changes, using the 'paired end' strategy. This reveals more clearly than before the extent to which many cancer genomes are rearranged and how much these rearrangements contribute to the mutational burden of epithelial tumors. In particular, there are probably many fusion genes, analogous to those found in leukemias, to be found in common cancers, such as breast carcinoma, and some of these will prove to be important in cancer diagnosis and treatment.
Genetic and temporal control of neonatal antibody expression.
Authors: K A Denis, N R Klinman
Journal: The Journal of Experimental Medicine (1983)

Two hybridoma cell lines were established with B cells derived from neonatal BALB/c spleen cells. The anti-dinitrophenyl (DNP) antibodies derived from these lines were characterized with respect to their isotype, affinity, and isoelectric point. Antiidiotypic reagents were prepared that permit an analysis of the representation of antibodies sharing idiotype with these two hybridomas in the developing and mature B cell pool of BALB/c mice (Igha) and other murine strains. One of the two antibodies, TF2-36, was found to be indistinguishable from 14% of anti-DNP monoclonal antibodies derived in fragment culture from spleen cells of 1-4-d-old BALB/c donors. B cells expressing this idiotype were found to represent approximately 2% of the anti-DNP-specific repertoire after the 1st wk of neonatal development and into adulthood. The second hybridoma antibody, TF2-76, was found to be expressed at very low levels during the first several days of neonatal development; however, B cells expressing this idiotype increased in frequency during the 2nd wk of neonatal development representing 7% of all DNP-responsive B cells 12-13 d after birth. The proportion of B cells expressing this idiotype also decreased to approximately 2% in adults. The relatively late appearance of B cells bearing this idiotype was confirmed by their susceptibility to tolerance induction after the 1st wk of neonatal development. Both the early neonatal clonotype, TF2-36, and the late neonatal antibody clonotype, TF2-76, were found to be expressed in a similar fashion in F1 mice constructed between Igha and Ighb parentals, but both were expressed at very low levels during the development of Ighb mice. Thus, the control of the magnitude of expression of these neonatal clonotypes appears to be associated with the Igh locus.
Nitro-Oleic Acid Inhibits Angiotensin II–Induced Hypertension
Authors: Jifeng Zhang, Luis Villacorta, Lin Chang, Zhenzhen Fan, Milton Hamblin, Tianqing Zhu, Chen S. Chen, Marsha P. Cole, Francisco J. Schopfer, Cheri X. Deng, Minerva T. Garcia-Barrio, Ying-Hong Feng, Bruce A. Freeman, Y. Eugene Chen
Journal: Circulation Research (2010)

Nitro-oleic acid (OA-NO(2)) is a bioactive, nitric-oxide derived fatty acid with physiologically relevant vasculoprotective properties in vivo. OA-NO(2) exerts cell signaling actions as a result of its strong electrophilic nature and mediates pleiotropic cell responses in the vasculature.The present study sought to investigate the protective role of OA-NO(2) in angiotensin (Ang) II-induced hypertension.We show that systemic administration of OA-NO(2) results in a sustained reduction of Ang II-induced hypertension in mice and exerts a significant blood pressure lowering effect on preexisting hypertension established by Ang II infusion. OA-NO(2) significantly inhibits Ang II contractile response as compared to oleic acid (OA) in mesenteric vessels. The improved vasoconstriction is specific for the Ang II type 1 receptor (AT(1)R)-mediated signaling because vascular contraction by other G-protein-coupled receptors is not altered in response to OA-NO(2) treatment. From the mechanistic viewpoint, OA-NO(2) lowers Ang II-induced hypertension independently of peroxisome proliferation-activated receptor (PPAR)gamma activation. Rather, OA-NO(2), but not OA, specifically binds to the AT(1)R, reduces heterotrimeric G-protein coupling, and inhibits IP(3) (inositol-1,4,5-trisphosphate) and calcium mobilization, without inhibiting Ang II binding to the receptor.These results demonstrate that OA-NO(2) diminishes the pressor response to Ang II and inhibits AT(1)R-dependent vasoconstriction, revealing OA-NO(2) as a novel antagonist of Ang II-induced hypertension.
Intensive attention improves glycaemic control in insulin dependent diabetes without further advantage from home blood glucose monitoring.
Authors: R H Harrad, A P Plumb, S Prickett, F P Alford, P H Sonksen
Journal: BMJ (1983)

munity Medicine, the Community Medicine Consultative Committee, the Department of Health and Social Security, and the BCG Vaccination Subcommittee of the Joint Tuberculosis Committee on Vaccination and Immunisation.It is important that all doctors who diagnose tuberculosis, both pulmonary and non- pulmonary, ensure that their cases are notified according to the public health regula- tions.We appreciate that doctors in many specialties encounter tuberculosis only occasionally, and it is particularly these cases which may miss being notified unless special care is taken.The value of this survey would undoubtedly be enhanced if all cases in 1983 are in fact notified.
p53 independent induction of PUMA mediates intestinal apoptosis in response to ischaemia-reperfusion
Authors: B. Wu, W. Qiu, P. Wang, H. Yu, T. Cheng, G. P Zambetti, L. Zhang, J. Yu
Journal: Gut (2006)

<b>Background:</b> The small intestine is highly sensitive to ischaemia–reperfusion (I/R) induced injury which is associated with high morbidity and mortality. Apoptosis, or programmed cell death, is a major mode of cell death occurring during I/R induced injury. However, the mechanisms by which I/R cause apoptosis in the small intestine are poorly understood. p53 upregulated modulator of apoptosis (<i>PUMA</i>) is a p53 downstream target and a member of the BH3-only group of Bcl-2 family proteins. It has been shown that <i>PUMA</i> plays an essential role in apoptosis induced by a variety of stimuli in different tissues through a mitochondrial pathway. <b>Aims:</b> The role of <i>PUMA</i> in I/R induced injury and apoptosis in the small intestine was investigated. The mechanisms by which <i>PUMA</i> is regulated in I/R induced intestinal apoptosis were also studied. <b>Methods:</b> Ischaemia was induced by superior mesenteric artery occlusion in the mouse small intestine. Induction of <i>PUMA</i> in response to ischaemia alone, or ischaemia followed by reperfusion (I/R), was examined. I/R induced intestinal apoptosis and injury were compared between <i>PUMA</i> knockout and wild-type mice. The mechanisms of I/R induced and <i>PUMA</i> mediated apoptosis were investigated through analysis of caspase activation, cytosolic release of mitochondrial cytochrome <i>c</i> and alterations of the proapoptotic Bcl-2 family proteins Bax and Bak. To determine whether <i>PUMA</i> is induced by reactive oxygen species and/or reactive nitrogen species generated by I/R, superoxide dismutase (SOD) and N-nitro-l-arginine methyl ester (L-NAME) were used to treat animals before I/R. To determine whether p53 is involved in regulating <i>PUMA</i> during I/R induced apoptosis, <i>PUMA</i> induction and apoptosis in response to I/R were examined in <i>p53</i> knockout mice. <b>Results:</b><i>PUMA</i> was markedly induced following I/R in the mucosa of the mouse small intestine. I/R induced intestinal apoptosis was significantly attenuated in <i>PUMA</i> knockout mice compared with that in wild-type mice. I/R induced caspase 3 activation, cytochrome <i>c</i> release, Bax mitochondrial translocation and Bak multimerisation were also inhibited in <i>PUMA</i> knockout mice. SOD or L-NAME significantly blunted I/R induced <i>PUMA</i> expression and apoptosis. Furthermore, I/R induced <i>PUMA</i> expression and apoptosis in the small intestine were not affected in the <i>p53</i> knockout mice. <b>Conclusions:</b> Our data demonstrated that <i>PUMA</i> is activated by oxidative stress in response to I/R to promote p53 independent apoptosis in the small intestine through the mitochondrial pathway. Inhibition of <i>PUMA</i> is potentially useful for protecting against I/R induced intestinal injury and apoptosis.
Randomised, double blind, placebo-controlled trial of selenium supplementation in adult asthma
Authors: S. O Shaheen, R. B Newson, M. P Rayman, A. P-L Wong, M. K Tumilty, J. M Phillips, J. F Potts, F. J Kelly, P. T White, P. G J Burney
Journal: Thorax (2007)

<b>Background:</b> Epidemiological evidence from observational studies has suggested that blood levels and dietary intake of selenium of adults with asthma are lower than those of controls. The only previous trial of selenium supplementation in adults with asthma found no objective evidence of benefit but involved only 24 participants. <b>Methods:</b> A randomised, double blind, placebo-controlled trial of selenium supplementation was performed in adults with asthma in London, UK, the majority of whom (75%) reported inhaled steroid use at baseline. 197 participants were randomised to receive either a high-selenium yeast preparation (100 µg daily, n = 99) or placebo (yeast only, n = 98) for 24 weeks. The primary outcome was asthma-related quality of life (QoL) score. Secondary outcomes included lung function, asthma symptom scores, peak flow and bronchodilator usage. Linear regression was used to analyse the change in outcome between the two treatment arms by "intention to treat". <b>Results:</b> There was a 48% increase in plasma selenium between baseline and end of trial in the active treatment group but no change in the placebo group. While the QoL score improved more in the active treatment group than in the placebo group, the difference in change in score between the two groups was not significant (−0.05 (95% CI −0.19 to 0.09); p = 0.47). Selenium supplementation was not associated with any significant improvement in secondary outcomes compared with placebo. <b>Conclusions:</b> Selenium supplementation had no clinical benefit in adults with asthma, the majority of whom were taking inhaled steroids.
Systems biology analysis of gene expression data and gene network reverse-engineering approaches reveal NFAT5 as a candidate biomarker in Inflammatory Breast Cancer
Authors: Andrea Remo, Ines Simeone, Massimo Pancione, Pietro Parcesepe, Pascal Finetti, Halima Bensmail, Luigi Cerulo, Vittorio Colantuoni, Daniel Birnbaum, Franco Bonetti, Francois Bertucci, Erminia Manfrin, Michele Ceccarelli
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Inflammatory Breast Cancer (IBC) is the most aggressive and highly metastatic form of breast cancer [[1][1]–[3][2]]. In a recent study [[4][3]], we analysed breast cancer with peritumoral neoplastic lymphovascular invasion (ePVI) in comparison with inflammatory breast cancer,
In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn's disease and non-smokers develop ulcerative colitis
Authors: S Bridger, J C W Lee, I Bjarnason, J E L. Jones, A J Macpherson
Journal: Gut (2002)

<b>Background and aims:</b> Smoking tobacco has opposite effects on the different forms of inflammatory bowel disease (IBD). It predisposes to the development of Crohn9s disease (CD) yet is associated with a reduced incidence of ulcerative colitis (UC). We have studied sib pairs discordant for both smoking and IBD phenotype (UC or CD) to investigate whether smoking determines the type of IBD that develops in individuals with very similar genetic susceptibility. <b>Patients:</b> Smoking habits and disease characteristics were analysed in 242 IBD pedigrees (658 patients). Within this group there were 339 affected sibling pairs of whom 89 were discordant for smoking when diagnosed. <b>Results:</b> Smoking at diagnosis was associated with development of CD (odds ratio (OR) 3.55; 95% confidence limits 2.50–5.02; p&lt;0.001) in all of the familial patients, with increases when analysed for ileocaecal disease, fibrostenosis, and intestinal resection. Smokers were also protected from UC (OR 0.28; 0.2–0.4; p&lt;0.001). Of 89 sibling pairs discordant for smoking at diagnosis, 23 were also discordant for disease type—in 21 of these, CD occurred in the smoker and UC in the non-smoker (OR 10.5; 2.6–92; p&lt;0.0001). <b>Conclusions:</b> Smoking is a strong environmental risk factor for Crohn9s disease and increases the likelihood of needing surgery. However, sib pairs who are discordant for both smoking and IBD type almost always show CD in the smoker and UC in the non-smoker, and so in some cases tobacco consumption acts on IBD genetic predisposition to shift the phenotype from UC towards CD. The explanation of part of the apparent "protective" effect of smoking on sporadic UC may be that the form of IBD that develops in a proportion of smokers is not UC but CD.
Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol
Authors: N Pearce, S Weiland, U Keil, P Langridge, HR Anderson, D Strachan, A Bauman, L Young, P Gluyas, D Ruffin, al. et
Journal: European Respiratory Journal (1993)

There is a need for a standardized approach to international and regional comparisons of the prevalence and severity of asthma, and for the monitoring of asthma morbidity over time. In 1991, standardized written and video questionnaires were developed and administered in surveys of schoolchildren, aged 12-15 yrs, in five regions in four countries: Adelaide, Australia (n = 1,428); Sydney, Australia (n = 1519); West Sussex, England (n = 2,097); Bochum, Germany (n = 1928); and Wellington, New Zealand (n = 1863). The self-reported prevalence of wheezing during the previous 12 months was similar in West Sussex (29% using the written questionnaire and 30% using the video questionnaire), Wellington (28 and 36%), Adelaide (29 and 37%), and Sydney (30 and 40%), but was lower in Bochum (20 and 27%). The one year prevalence of severe wheezing limiting speech was greater in Wellington (11%), Adelaide (10%) and Sydney (13%), than in West Sussex (7%) and Bochum (6%). The self-reported one year prevalences of frequent attacks, frequent nocturnal wheezing, and doctor diagnosed asthma, were also higher in the Australasian centres than in the European centres. We conclude, that an international comparison of asthma symptom prevalence in childhood, using simple standardized instruments, is feasible. Possible explanations for the differences in reported asthma severity between the Australasian and European centres include differences in exposure to risk factors and differences in the management of asthma.
Risk of endometrial cancer after tamoxifen treatment of breast cancer
Authors: F.E. van Leeuwen, A.W. van den Belt-Dusebout, F.E. van Leeuwen, J. Benraadt, F.W. Diepenhorst, H. van Tinteren, J.W.W. Coebergh, L.A.L.M. Kiemeney, C.H.F. Gimbrère, R. Otter, L.J. Schouten, R.A.M. Damhuis, J. Benraadt, M. Bontenbal
Journal: The Lancet (1994)
The global burden of listeriosis: a systematic review and meta-analysis
Authors: Charline Maertens de Noordhout, Brecht Devleesschauwer, Frederick J Angulo, Geert Verbeke, Juanita Haagsma, Martyn Kirk, Arie Havelaar, Niko Speybroeck
Journal: The Lancet Infectious Diseases (2014)
Physician Well-being
Authors: Lara Goitein
Journal: JAMA Internal Medicine (2014)

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Reply to Letter to the Editor ‘Concurrent oxaliplatin, capecitabine, and radiation therapy in the neoadjuvant therapy of rectal adenocarcinoma: can we get the right dose first?’, by M. G. Fakih (Ann Oncol 2006; 17: 1029)
Authors: J.-P. Machiels, P. Scalliet
Journal: Annals of Oncology (2006)