tbuckley/cabot-search huggingface dataset:
CBFB–MYH11/RUNX1 together with a compendium of hematopoietic regulators, chromatin modifiers and basal transcription factors occupies self-renewal genes in inv(16) acute myeloid leukemia
Authors: A Mandoli, A A Singh, P W T C Jansen, A T J Wierenga, H Riahi, G Franci, K Prange, S Saeed, E Vellenga, M Vermeulen, H G Stunnenberg, J H A Martens
Journal: Leukemia (2013)

Different mechanisms for CBFβ–MYH11 function in acute myeloid leukemia with inv(16) have been proposed such as tethering of RUNX1 outside the nucleus, interference with transcription factor complex assembly and recruitment of histone deacetylases, all resulting in transcriptional repression of RUNX1 target genes. Here, through genome-wide CBFβ–MYH11-binding site analysis and quantitative interaction proteomics, we found that CBFβ–MYH11 localizes to RUNX1 occupied promoters, where it interacts with TAL1, FLI1 and TBP-associated factors (TAFs) in the context of the hematopoietic transcription factors ERG, GATA2 and PU.1/SPI1 and the coregulators EP300 and HDAC1. Transcriptional analysis revealed that upon fusion protein knockdown, a small subset of the CBFβ–MYH11 target genes show increased expression, confirming a role in transcriptional repression. However, the majority of CBFβ–MYH11 target genes, including genes implicated in hematopoietic stem cell self-renewal such as ID1, LMO1 and JAG1, are actively transcribed and repressed upon fusion protein knockdown. Together these results suggest an essential role for CBFβ–MYH11 in regulating the expression of genes involved in maintaining a stem cell phenotype.
Interleukin-17A Modulates Circulating Tumor Cells in Tumor Draining Vein of Colorectal Cancers and Affects Metastases
Authors: Ju-Yu Tseng, Chih-Yung Yang, Shu-Ching Liang, Ren-Shyan Liu, Shung-Haur Yang, Jen-Kou Lin, Yuh-Min Chen, Yu-Chung Wu, Jeng-Kai Jiang, Chi-Hung Lin
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Metastasis is the major cause of death in patients with colorectal cancer (CRC). Circulating tumor cells (CTC) are believed to cause metastasis and serve as a prognostic marker for mortality in clinical stage IV patients. However, most studies are conducted in late-stage cases when distant metastases have already occurred; thus, such results provide limited clinical use. This study focused on whether CTCs can predict the risk of metastasis after treatment of the primary tumor in early-stage patients with CRC. Experimental Design: CTCs were quantified using EpCAM-positive/CD45-negative immunoselection and flow cytometry in patients with CRC. A mouse model was used to investigate the mechanistic roles of CTCs and interleukin (IL)-17A in metastasis. Results: The number of mesenteric CTCs obtained from stage II patients was higher than that obtained from patients in stages I, III, and IV. In addition, following invasion of orthotopically implanted tumors in our mouse model, we found that CTCs exhibited an increase-then-decrease pattern, accompanied by corresponding changes in serum IL-17A levels and opposing changes in serum granulocyte macrophage colony-stimulating factor (GM-CSF) levels. Ablation of IL-17A and administration of rGM-CSF effectively suppressed the increase in CTCs and prevented metastasis in mice. Moreover, IL-17A promoted cancer cell motility, matrix digestion, and angiogenesis, whereas GM-CSF stimulated the elimination of CTCs by boosting host immunity. Notably, serum levels of IL-17A were also correlated with disease-free survival in patients with CRC. Conclusions: Our results showed that CTCs and IL-17A could serve as prognostic markers and therapeutic targets for CRC metastasis. Clin Cancer Res; 20(11); 2885–97. ©2014 AACR.
Expansion of innate CD5pos B cells expressing high levels of CD81 in hepatitis C virus infected liver
Authors: Michael P. Curry, Lucy Golden-Mason, Derek G. Doherty, Tina Deignan, Suzanne Norris, Margaret Duffy, Niamh Nolan, William Hall, John E. Hegarty, Cliona O'Farrelly
Journal: Journal of Hepatology (2003)
ENCEPHALOPATHY FOLLOWING INJECTIONS OF BONE MARROW EXTRACT
Authors: Lester S. King
Journal: The Journal of Experimental Medicine (1939)

Monkey bone marrow extract when injected intracerebrally into guinea pigs or rabbits produces a distinctive encephalopathy. The Purkinje cells are severely affected, especially those at the periphery of the cerebellum. Nuclear alterations first appear, with well marked intranuclear acidophilic inclusion bodies. Similar inclusions appear at a little later stage in the ectodermal glia. The affected cells later become necrotic and usually disappear. The reaction is essentially glial and non-inflammatory, and hence is called encephalopathy rather than encephalitis. A hyaline necrosis of cerebral blood vessels, especially at the base of the brain, is described. Small areas of softening may appear in the cerebellum as a result, but this is considered a secondary process, independent of the Purkinje cell loss. There may also inconstantly be found a loss of cerebellar granule cells and a selective necrosis of the hippocampal pyramidal cells. Secondary and reparative reactions are described. Similar changes are produced by extracts of lymph nodes from Hodgkin's disease, and by leucocytic cream of human blood. A tentative explanation of the pathogenesis is suggested, and similarities to certain virus diseases are pointed out.
Genetic Admixture History of Eastern Indonesia as Revealed by Y-Chromosome and Mitochondrial DNA Analysis
Authors: S. Mona, K. E. Grunz, S. Brauer, B. Pakendorf, L. Castri, H. Sudoyo, S. Marzuki, R. H. Barnes, J. Schmidtke, M. Stoneking, M. Kayser
Journal: Molecular Biology and Evolution (2009)

Eastern Indonesia possesses more linguistic diversity than any other region in Southeast Asia, with both Austronesian (AN) languages that are of East Asian origin, as well as non-Austronesian (NAN) languages of likely Melanesian origin. Here, we investigated the genetic history of human populations from seven eastern Indonesian islands, including AN and NAN speakers, as well as the relationship between languages and genes, by means of nonrecombining Y-chromosomal (NRY) and mitochondrial DNA (mtDNA) analysis. We found that the eastern Indonesian gene pool consists of East Asian as well as Melanesian components, as might be expected based on linguistic evidence, but also harbors putative indigenous eastern Indonesian signatures that perhaps reflect the initial occupation of the Wallacea by aboriginal hunter-gatherers already in Palaeolithic times. Furthermore, both NRY and mtDNA data showed a complete lack of correlation between linguistic and genetic relationships, most likely reflecting genetic admixture and/or language shift. In addition, we noted a small fraction of the NRY and mtDNA data shared between eastern Indonesians and Australian Aborigines likely reflecting an ancient link between Asia and Australia. Our data thus provide insights into the complex genetic ancestry history of eastern Indonesian islanders characterized by several admixture episodes and demonstrate a clear example of the lack of the often-assumed correlation between the genes and languages of human populations.
<i>In vivo</i> Loss of Expression of Argininosuccinate Synthetase in Malignant Pleural Mesothelioma Is a Biomarker for Susceptibility to Arginine Depletion
Authors: Peter W. Szlosarek, Astero Klabatsa, Arben Pallaska, Michael Sheaff, Paul Smith, Tim Crook, Matthew J. Grimshaw, Jeremy P. Steele, Robin M. Rudd, Frances R. Balkwill, Dean A. Fennell
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Malignant pleural mesothelioma (MPM) is an increasing health burden on many societies worldwide and, being generally resistant to conventional treatment, has a poor prognosis with a median survival of &amp;lt;1 year. Novel therapies based on the biology of this tumor seek to activate a proapoptotic cellular pathway. In this study, we investigated the expression and biological significance of argininosuccinate synthetase (AS), a rate-limiting enzyme in arginine production. Experimental Design: Initially, we documented down-regulation of AS mRNA in three of seven MPM cell lines and absence of AS protein in four of seven MPM cell lines. We confirmed that the 9q34 locus, the site of the AS gene, was intact using a 1-Mb comparative genomic hybridization array; however, there was aberrant promoter CpG methylation in cell lines lacking AS expression, consistent with epigenetic regulation of transcription. To investigate the use of AS negativity as a therapeutic target, arginine was removed from the culture medium of the MPM cell lines. Results: In keeping with the cell line data, 63% (52 of 82) of patients had tumors displaying reduced or absent AS protein, as assessed using a tissue microarray. Cell viability declined markedly in the AS-negative cell lines 2591 and MSTO but not in the AS-positive cell line, 28. This response was apparent by day 4 and maintained by day 9 in vitro. Arginine depletion induced BAX conformation change and mitochondrial inner membrane depolarization selectively in AS-negative MPM cells. Conclusions: In summary, we have identified AS negativity as a frequent event in MPM in vivo, leading to susceptibility to cytotoxicity following restriction of arginine. A phase II clinical trial is planned to evaluate the role of arginine depletion in patients with AS-negative MPM.
Ten-Year Experience of Chordal Replacement With Expanded Polytetrafluoroethylene in Mitral Valve Repair
Authors: J Kobayashi, Y Sasako, K Bando, K Minatoya, K Niwaya, S Kitamura
Journal: Circulation (2000)

Mitral valve repair is the procedure of choice to correct mitral regurgitation (MR). Although chordal replacement with expanded polytetrafluoroethylene (ePTFE) has been widely accepted to repair anterior mitral prolapse and other difficult situations, the long-term results of the repair and the fate of ePTFE have not been delineated.From July 1988 to April 1999, 74 patients (49 males, 25 females) aged 17 to 77 years (mean age 55. 3+/-14.8 years) underwent mitral valve repair with chordal replacement with ePTFE. The follow-up period was from 6 months to 11. 3 years (mean 4.6+/-3.2 years). The causes of MR were degenerative in 65 patients (88%) and infective in 9 (12%). Three patients had active infective endocarditis. Valve lesions were anterior in 35 patients, posterior in 10, and both anterior and posterior in 29. Various procedures for plasty of leaflets were necessary in 37 patients (50%). Atrial fibrillation was associated in 38 patients (51%), and the maze procedure has been performed in a selected group of 30 patients (41%) since July 1992. There was 1 in-hospital death (1.4%) and 3 late cardiac deaths (4.1%). More than moderate MR developed in 12 patients (17%) during the follow-up period. Three of these patients required early reoperation within 1 year due to hemolysis. Two patients underwent mitral valve replacement at 6 and 8 years after repair, respectively. The actuarial reoperation-free rates at 5 and 10 years were 94.3+/-2.8% and 81.7+/-9.1%, respectively. Sinus rhythm was restored in 21 patients (70%) with the maze procedure. There was only 1 thromboembolic episode (0. 3%/patient-y) in a patient with atrial fibrillation who did not undergo the maze procedure. Event-free survival rates as assessed by the freedom from cardiac death, thromboembolism, reoperation, and anticoagulation-related hemorrhage at 5 and 10 years were 91.3+/-3. 4% and 71.6+/-9.7%, respectively. There was no relationship between recurrent MR and the change of ePTFE. Structural analysis of the ePTFE resected during reoperation revealed no calcification and showed remaining flexibility and pliability. Protein infiltration was observed in the ePTFE, and collagenous proliferation was recognized at the site of fixation to the valve leaflet and the papillary muscle. The surface of the ePTFE was completely endothelialized, which may induce antithrombogenicity.The long-term durability and biological adaptation of ePTFE as artificial chordae for mitral valve repair of MR were proved for >10 years.
Emerging Data Continue to Find Lack of Benefit for Vitamin-Mineral Supplement Use
Authors: Mike Mitka
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Decrease in serum immunoreactive parathyroid hormone in rats and in parathyroid hormone secretion in vitro by 1,25-dihydroxycholecalciferol.
Authors: B S Chertow, D J Baylink, J E Wergedal, M H Su, A W Norman
Journal: Journal of Clinical Investigation (1975)

The present study determined the effects of 1,25-dihydroxycholecalciferol on serum immunoactive parathyroid hormone and on parathyroid hormone secretion in vitro. Rats injected i.p. with 1,25-dihydroxycholecalciferol, 130 pmol (2 U)/140 g body wt, which is probably a physiologic dose, had a significant 43% decrease in serum immunoreactive parathyroid hormone at 4 h. In addition, this dose of 1,25-dihydroxycholecalciferol inhibited the serum immunoreactive parathyroid hormone response to hypocalcemia induced by phosphate injection. Because the increment in serum immunoreactive parathyroid hormone was less but the decrement in serum calcium more in phosphate plus 1,25-dihydroxycholecalciferol-treated than in phosphate plus vehicle-treated rats, the impaired serum immunoreactive parathyroid hormone response to 1,25-dihydroxycholecalciferol could not be attributed to the change in serum calcium. In studies of parathyroid hormone secretion from bovine parathyroid tissue in vitro, the concentration of 1,25-dihydroxycholecalciferol used for most experiments was 1nM, which is in the range found in rat serum. 1,25-Dihydroxycholecalciferol at 1 or 100 nM significantly inhibited parathyroid hormone secretion when medium calcium concentration was normal (1.5 mM), high (3.0 mM), and low (1.0 mM). Maximum inhibition ranged from 19 to 74%; inhibition was generally seen after 2 h of incubation; and inhibition was sustained or progressive thereafter. Vitamin A, 0.1 muM, caused a marked stimulation of parathyroid hormone secretion. 1,25-Dihydroxycholecalciferol at 1 nM markedly reduced (44%) the effect of vitamin A to stimulate parathyroid hormone secretion. This effect of 1,25-dihydroxycholecalciferol was maximal at 1 h and persisted thereafter. Another steroid, hydrocortisone, 10 muM, did not inhibit parathyroid hormone secretion, suggesting that the 1,25-dihydroxycholecalciferol effect was not a nonspecific inhibitory effect on parathyroid cells. Because other workers have shown that parathyroid hormone directly stimulates 1,25-dihydroxycholecalciferol secretion, our results are consistent with the concept that there is a feedback loop where parathyroid hormone directly stimulates secretion of 1,25-dihydroxycholecalciferol, which in turn directly inhibits secretion of parathyroid hormone.
Twist Overexpression Correlates with Hepatocellular Carcinoma Metastasis through Induction of Epithelial-Mesenchymal Transition
Authors: Terence K. Lee, Ronnie T.P. Poon, Anthony P. Yuen, Ming Tat Ling, Wei Kei Kwok, Xiang Hong Wang, Yong Chuan Wong, Xin Yuan Guan, Kwan Man, King Lok Chau, Sheung Tat Fan
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Hepatocellular carcinoma (HCC) is a rapidly growing tumor associated with a high propensity for vascular invasion and metastasis. Epithelial-mesenchymal transition (EMT) is a key event in the tumor invasion process. Recently, Twist has been identified to play an important role in EMT-mediated metastasis through the regulation of E-cadherin expression. However, the actual role of Twist in tumor invasiveness remains unclear. The purpose of this study is to investigate the expression and possible role of Twist in HCC. Experimental Design: We evaluated Twist and E-cadherin expression in HCC tissue microarray of paired primary and metastatic HCC by immunohistochemical staining. The role of Twist in EMT-mediated invasiveness was also evaluated in vitro in HCC cell lines. Results: We first showed that overexpression of Twist was correlated with HCC metastasis (P = 0.001) and its expression was negatively correlated with E-cadherin expression (P = 0.001, r = −0.443) by tissue microarray. A significant increase of Twist at the mRNA level was also found in metastatic HCC cell lines MHCC-97H, MHCC-97L, and H2M when compared with nonmetastatic Huh-7, H2P, and PLC cell lines. The MHCC-97H cell line, which has a higher metastatic ability, was found to have a higher level of Twist than MHCC-97L. Accompanied with increased Twist expression in the metastatic HCC cell lines when compared with the nonmetastatic primary ones, we found decreased E-cadherin mRNA expression in the metastatic HCC cell lines. By ectopic transfection of Twist into PLC cells, Twist was able to suppress E-cadherin expression and induce EMT changes, which was correlated with increased HCC cell invasiveness. Conclusion: This study shows that Twist overexpression was correlated with HCC metastasis through induction of EMT changes and HCC cell invasiveness.
A randomized controlled evaluator-blinded trial of intravenous immunoglobulin in adults with severe atopic dermatitis
Authors: C. Paul, M. Lahfa, H. Bachelez, S. Chevret, L. Dubertret
Journal: British Journal of Dermatology (2002)

There is a need for alternative therapy in severe adult atopic dermatitis (AD). Intravenous immunoglobulin (IVIG) treatment has been shown to be beneficial in a few open observations, but evidence of effectiveness is still lacking.To investigate whether treatment with IVIG is effective in adults with severe AD.In a randomized evaluator-blinded trial, 10 patients with severe AD were randomized to immediate or delayed (by 1 month) treatment with IVIG 2 g kg-1. Patients received an 8-h infusion of 1 g kg-1 daily for two consecutive days. They were assessed clinically at days 15, 30, 60 and 90. The primary efficacy criterion was measurement of the severity scoring of AD (SCORAD) index at day 30.The SCORAD values were not significantly different between the two groups at day 30. Similarly, global evaluation of disease severity by patients did not show any clinically significant change at day 30. In the cohort of 10 patients, the mean percentage decrease in SCORAD as compared with baseline was, respectively, 15%[95% confidence interval (CI) 6-24%] and 22% (95% CI 5-39%) at 30 and 60 days after IVIG infusion.IVIG treatment was not associated with clinically significant improvement of AD signs and symptoms in this randomized study. Although this study may have been too small to detect a beneficial effect in a small subset of patients, the results do not support the common use of IVIG in refractory AD.
Pacemaker explosions in crematoria: problems and possible solutions
Authors: C. P Gale, G. P Mulley
Journal: Journal of the Royal Society of Medicine (2002)

The number of artificial cardiac pacemakers is increasing, as is the number of bodies being cremated. Because of the explosive potential of pacemakers when heated, a statutory question on the cremation form asks whether the deceased has a pacemaker and if so whether it has been removed. We sent a questionnaire to all the crematoria in the UK enquiring about the frequency, consequences and prevention of pacemaker explosions. We found that about half of all crematoria in the UK experience pacemaker explosions, that pacemaker explosions may cause structural damage and injury and that most crematoria staff are unaware of the explosive potential of implantable cardiac defibrillators. Crematoria staff rely on the accurate completion of cremation forms, and doctors who sign cremation forms have a legal obligation to provide such information.
Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial
Authors: Jack Cuzick, Ivana Sestak, David Cella, Lesley Fallowfield
Journal: The Lancet Oncology (2008)

BackgroundWhen the mechanism of action behind treatment toxicity reflects the intended effect on the treatment target, the toxicity might be a useful marker for efficacy. During endocrine treatment of breast cancer, the occurrence of symptoms related to oestrogen depletion or oestrogen blockade might thus be a predictor of treatment effectiveness. In this retrospective analysis, the relation between the reported incidence of vasomotor or joint symptoms and breast cancer recurrence in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial is assessed.MethodsWomen with hormone-receptor-positive tumours who reported vasomotor or joint symptoms at the first follow-up visit (3 months) in the ATAC trial, (which assessed tamoxifen or anastrozole for adjuvant treatment of postmenopausal breast cancer), were compared with women without these symptoms to see if there was a relation between these symptoms and subsequent recurrence. The ATAC trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230.Findings1486 of 3964 (37·5%) eligible women reported newly emergent vasomotor symptoms at the 3-month follow-up visit and had lower subsequent recurrence than those who did not report these symptoms (223 during 10 752 women-years of follow-up vs 366 during 11 573 woman-years of follow-up, respectively; hazard ratio [HR] 0·84 [95% CI 0·71–1·00], p=0·04; adjusted for age, body-mass index, previous hormone-replacement therapy, nodal status, tumour size, and tumour grade). A greater decrease in breast-cancer recurrence was seen for the 1245 of 3964 (31·4%) eligible women who reported new joint symptoms at the 3-month follow-up visit compared with those not reporting these symptoms (158 during 9242 women-years of follow-up vs 366 during 11 573 women-years of follow-up; adjusted HR 0·60 [0·50–0·72], p<0·0001).InterpretationThe appearance of new vasomotor symptoms or joint symptoms within the first 3 months of treatment is a useful biomarker, suggesting a greater response to endocrine treatment compared with women without these symptoms. Awareness of the relation between early treatment-emergent symptoms and beneficial response to therapy might be useful when reassuring patients who present with them, and might help to improve long-term treatment adherence when symptoms cannot be alleviated effectively.FundingCancer Research UK and AstraZeneca.