tbuckley/cabot-search huggingface dataset:
Haploinsufficiency of the <i>Hmga1</i> Gene Causes Cardiac Hypertrophy and Myelo-Lymphoproliferative Disorders in Mice
Authors: Monica Fedele, Vincenzo Fidanza, Sabrina Battista, Francesca Pentimalli, Andres J.P. Klein-Szanto, Rosa Visone, Ivana De Martino, Antonio Curcio, Carmine Morisco, Luigi Del Vecchio, Gustavo Baldassarre, Claudio Arra, Giuseppe Viglietto, Ciro Indolfi, Carlo M. Croce, Alfredo Fusco
Journal: Cancer Research (2006)

The HMGA1 protein is a major factor in chromatin architecture and gene control. It plays a critical role in neoplastic transformation. In fact, blockage of HMGA1 synthesis prevents rat thyroid cell transformation by murine transforming retroviruses, and an adenovirus carrying the HMGA1 gene in the antisense orientation induces apoptotic cell death in anaplastic human thyroid carcinoma cell lines, but not in normal thyroid cells. Moreover, both in vitro and in vivo studies have established the oncogenic role of the HMGA1 gene. In this study, to define HMGA1 function in vivo, we examined the consequences of disrupting the Hmga1 gene in mice. Both heterozygous and homozygous mice for the Hmga1-null allele show cardiac hypertrophy due to the direct role of HMGA1 on cardiomyocytic cell growth regulation. These mice also developed hematologic malignancies, including B cell lymphoma and myeloid granuloerythroblastic leukemia. The B cell expansion and the increased expression of the RAG1/2 endonuclease, observed in HMGA1-knockout spleen tissues, might be responsible for the high rate of abnormal IgH rearrangements observed in these neoplasias. Therefore, the data reported here indicate the critical role of HMGA1 in heart development and growth, and reveal an unsuspected antioncogenic potential for this gene in hematologic malignancies.
The significance of cagA+ Helicobacter pylori in reflux oesophagitis
Authors: V J Warburton-Timms
Journal: Gut (2001)

Helicobacter pylori is a gastroduodenal pathogen associated with ulceration, dyspepsia, and adenocarcinoma. Recent preliminary studies have suggested that H pylori may be protective for oesophageal adenocarcinoma. In addition, strains of H pylori identified by the presence of the cytotoxin associated gene A (cagA) are shown to have a significant inverse association with oesophageal adenocarcinoma. Given that cagA(+) H pylori may protect against oesophageal carcinoma, these strains may be protective for oesophagitis, a precursor of oesophageal carcinoma.The aim of this study was to investigate the association between cagA(+) H pylori and endoscopically proved oesophagitis.The study group included 1486 patients attending for routine upper gastrointestinal tract endoscopy.At endoscopy the oesophagus was assessed for evidence of reflux disease and graded according to standard protocols. Culture and histology of gastric biopsy specimens determined H pylori status. The prevalence of cagA was identified by an antibody specific ELISA (Viva Diagnostika, Germany).H pylori was present in 663/1485 (45%) patients and in 120/312 (38%) patients with oesophagitis. Anti-CagA antibody was found in 499/640 (78%) H pylori positive patients. Similarly, anti-CagA antibody was found in 422/521 (81%) patients with a normal oesophagus and in 42/60 (70%) with mild, 24/35 (69%) with moderate, and 11/24 (46%) with severe oesophagitis. The risk of severe oesophagitis was significantly decreased for patients infected with cagA(+) H pylori after correction for confounding variables (odds ratio 0.57, 95% confidence interval 0.41-0.80; p=0.001).These results suggest that infection by cagA(+) H pylori may be protective for oesophageal disease.
Discrimination of exudative pleural effusions based on multiple biological parameters
Authors: Z. D. Daniil, E. Zintzaras, T. Kiropoulos, A. I. Papaioannou, A. Koutsokera, A. Kastanis, K. I. Gourgoulianis
Journal: European Respiratory Journal (2007)

Pleural effusion is a common complication of various diseases. Conventional methods are not always capable of establishing the cause of pleural effusion, so alternative tests are needed. The aim of this study was to explore means of discriminating between different pleural effusion groups, malignant, parapneumonic and tuberculous, based on the combined function of seven biological markers. Adenosine deaminase (ADA), interferon-γ, C-reactive protein (CRP), carcinoembryonic antigen, interleukin-6, tumour necrosis factor-α and vascular endothelial growth factor concentration levels were measured in pleural fluid from 45 patients with malignant, 15 with parapneumonic and 12 with tuberculous pleural effusion. Receiver operating characteristic curve analysis, multinomial logit modelling and canonical variate analysis were applied to discriminate the pleural effusion groups. The three groups could be discriminated successfully using the measured markers. The most important parameters for discrimination were ADA and CRP concentration levels. An individual with an ADA concentration level of &gt;45 U·L<sup>−1</sup> and a CRP concentration of &lt;4 mg·dL<sup>−1</sup> was more likely to belong to the tuberculous pleural effusion group, whereas one with an ADA concentration level of &lt;40 U·L<sup>−1</sup> and a CRP concentration of &gt;6 mg·dL<sup>−1</sup> was more likely to belong to the parapneumonic pleural effusion group, and one with a CRP concentration of &lt;4 mg·dL<sup>−1</sup> to the malignant pleural effusion group. The combination of adenosine deaminase and C-reactive protein levels might be sufficient for discriminating between the three different groups of exudative pleural effusion: malignant, tuberculous and parapneumonic.
Abstract P2-09-33: Validity of Bone Marker Measurements for Monitoring Response to Bisphosphonate (BP) Therapy with Zoledronic Acid (ZOL) in Metastatic Breast Cancer (mBC): Useful or Not?
Authors: B Aktas, S Kasimir-Bauer, N Lehmann, R Kimmig, S. Kuemmel
Journal: Cancer Research (2010)

Abstract BACKGROUND: Bone is the most common site of metastasis in breast cancer. The detection relies on imaging technology which is costly and can only be performed to a certain degree. Bone markers are noninvasive, inexpensive and potentially might serve as predictive and prognostive surrogate endpoints in detecting bone metastases and response to BPs. This study analyzes the value of the serum markers of type I collagen synthesis (PINP) and degradation (ICTP) as markers of bone metastases in mBC patients (pts) receiving ZOL. The results will be correlated with the levels of CEA and Ca 15-3 as well as the clinical response. MATERIALS AND METHODS: 38 mBC pts (mean age was 60 years: range, 35-86), with confirmed bone metastases who were received chemotherapy and/or hormonal therapy and ZOL iv q 4 wks were participating in our study. 5 ml blood were collected at the time of study start and q 3 months for one year for the analysis of PINP, ICTP, CEA and Ca 15-3 using radioimmunoassays and ECLIA System, respectively. Imaging of bone metastases was performed at the same time points. In this first analysis, data were correlated with the number of bone metastases at study start. RESULTS: At study baseline, PINP, ICTP, CEA and Ca 15-3 were analyzed in all pts. In 28/38 pts (73%) more than 3 bone metastases were confirmed by imaging and 10/38 pts (27%) presented with 3 or less bone metastases. The median value for ICTP was 6 µg/l (interquartile range 3.9-12.7) and for PINP 58.7 µg/l (43.5-164). Serum PINP and ICTP concentrations were significantly different when pts were stratified into &amp;gt; 3 bone metastases (median value ICTP 6.3 µg/l and PINP 75.3 µg/l) and 3 or less bone metastases (median value ICTP 4.1 µg/l and PINP 47 µg/l), respectively (P&amp;lt;0.05, see Figure 1 for ICTP and 2 for PINP for logarithmized values). No significant differences were seen when tumor marker levels were correlated with the number of bone metastases (P&amp;gt;0.2). Statistical analysis for follow-up measurements will be available after having completed sampling for all 38 pts in 5 months. Up to now, 135 samples of all patients have been analyzed and there seems to be an association between the number of bone metastases, serum levels for PINP/ICTP and response to therapy. CONCLUSION: In contrast to serum tumor markers, the identification of PINP and ICTP permit to estimate the number of bone metastases and seems to be a useful tool for monitoring mBC pts undergoing BP therapy with ZOL for treatment of bone metastases. These results have to be confirmed in a larger prospective trial. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-33.
Validation of the Framingham Coronary Heart Disease Prediction Scores
Authors: Ralph B. D'Agostino, Scott Grundy, Lisa M. Sullivan, Peter Wilson
Journal: JAMA (2001)

<h3>Context</h3> The Framingham Heart Study produced sex-specific coronary heart disease (CHD) prediction functions for assessing risk of developing incident CHD in a white middle-class population. Concern exists regarding whether these functions can be generalized to other populations. <h3>Objective</h3> To test the validity and transportability of the Framingham CHD prediction functions per a National Heart, Lung, and Blood Institute workshop organized for this purpose. <h3>Design, Setting, and Subjects</h3> Sex-specific CHD functions were derived from Framingham data for prediction of coronary death and myocardial infarction. These functions were applied to 6 prospectively studied, ethnically diverse cohorts (n = 23 424), including whites, blacks, Native Americans, Japanese American men, and Hispanic men: the Atherosclerosis Risk in Communities Study (1987-1988), Physicians' Health Study (1982), Honolulu Heart Program (1980-1982), Puerto Rico Heart Health Program (1965-1968), Strong Heart Study (1989-1991), and Cardiovascular Health Study (1989-1990). <h3>Main Outcome Measures</h3> The performance, or ability to accurately predict CHD risk, of the Framingham functions compared with the performance of risk functions developed specifically from the individual cohorts' data. Comparisons included evaluation of the equality of relative risks for standard CHD risk factors, discrimination, and calibration. <h3>Results</h3> For white men and women and for black men and women the Framingham functions performed reasonably well for prediction of CHD events within 5 years of follow-up. Among Japanese American and Hispanic men and Native American women, the Framingham functions systematically overestimated the risk of 5-year CHD events. After recalibration, taking into account different prevalences of risk factors and underlying rates of developing CHD, the Framingham functions worked well in these populations. <h3>Conclusions</h3> The sex-specific Framingham CHD prediction functions perform well among whites and blacks in different settings and can be applied to other ethnic groups after recalibration for differing prevalences of risk factors and underlying rates of CHD events.
Genotype/phenotype correlation of the G85E mutation in a large cohort of cystic fibrosis patients
Authors: K. Decaestecker, E. Decaestecker, C. Castellani, M. Jaspers, H. Cuppens, K. De Boeck
Journal: European Respiratory Journal (2004)

In this European study, the phenotype in 68 patients, homozygous or compound heterozygous for the G85E mutation, was investigated. Each index case was compared with two cystic fibrosis (CF) patients from the same clinic, matched for age and sex: one with pancreatic sufficiency (PS) and one with pancreatic insufficiency (PI). When comparing 31 G85E/F508del and F508del/F508del patients, there were no differences in median age at diagnosis, mean sweat chloride value, most recent weight for height, most recent forced expiratory volume in one second % predicted, prevalence of chronic Pseudomonas aeruginosa colonisation and typical CF complications. However, PI was less frequent in the G85E/F508del group. Comparison of 55 G85E patients (with second mutation known and not classified as mild) with PS controls (n=44) showed that the G85E patients had a significantly higher sweat chloride, more often failure to thrive at diagnosis, higher prevalence of PI, worse current weight for height, higher prevalence of chronic P. aeruginosa colonisation and liver cirrhosis. Pulse-chase experiments revealed that G85E cystic fibrosis transmembrane conductance regulator failed to mature on a M470 as well as on a V470 background. Therefore, G85E is a class II mutation. Although there is variability in its clinical presentation, G85E mutation results in a severe phenotype.
Development of tuberculin reactivity and sensitization to M. Scrofulaceum and M. Fortuitum in children BCG-vaccinated at birth
Authors: L. Kröger, M. Korppi, J. Pelkonen, M Pietikäinen, M.L. Katila
Journal: European Respiratory Journal (2000)

Since the incidence of tuberculosis is steadily declining in Finland and infections by environmental mycobacteria may be increasing, the aim of the present study was to evaluate the development of tuberculin reactivity and sensitization to environmental mycobacteria. Healthy Finnish schoolchildren aged 10.4-12.4 yrs (n=201) were tested with tuberculin purified protein derivative RT23, Mycobacterium scrofulaceum RS95 and M. fortuitum RS20 sensitins. The same children had been previously tested with the same antigens and methods at the age of 4-6 yrs in 1989. Rapid waning of tuberculin reactivity and decrease in sensitization to environmental mycobacteria were observed between 4-6 yrs. Both tuberculin and sensitin skin reaction sizes decreased significantly over the 6-yrs period. The mean tuberculin skin reaction size was 3.2 mm in diameter, which was significantly (p&lt;0.001) smaller than the mean induration size (4.8 mm) at the age of 4-6 yrs. Similarly, the mean skin reaction sizes to M. scrofulaceum and M. fortuitum sensitins were 3.4 and 1.7 mm, respectively, which were significantly (p&lt;0.001) smaller than 6 yrs earlier (mean 4.5 and 3.1 mm). The number of zero reactions to all antigens increased significantly during the follow-up period. Contacts with pets or farm animals were associated with larger reactions. In contrast, children suffering from allergic symptoms had smaller reactions. Contacts with mycobacteria, either with Mycobacterium tuberculosis or environmental mycobacteria, seem to be too rare to maintain tuberculin responsiveness and a high sensitivity to other mycobacteria. Different bacille Calmette-Guerin vaccine products and dosages used, the declining incidence of tuberculosis and geographical factors, which can influence environmental mycobacterial exposure, may explain the disparity between the present and previous Finnish studies.
BLIND CONFIRMATION OF GECZY FACTOR IN ANKYLOSING SPONDYLITIS
Authors: J.J.Van Rood, A.Van Leeuwen, P. Ivanyi, A. Cats, B.S. Breur-Vriesendorp, A.J. Dekker-Saeys, A. Kijlstra, E.Van Kregten
Journal: The Lancet (1985)
Enforced Expression of <i>NUP98-HOXA9</i> in Human CD34+ Cells Enhances Stem Cell Proliferation
Authors: Ki Y. Chung, Giovanni Morrone, Jan Jacob Schuringa, Magdalena Plasilova, Jae-Hung Shieh, Yue Zhang, Pengbo Zhou, Malcolm A.S. Moore
Journal: Cancer Research (2006)

Abstract The t(7;11)(p15;p15) translocation, observed in acute myelogenous leukemia and myelodysplastic syndrome, generates a chimeric gene where the 5′ portion of the sequence encoding the human nucleoporin NUP98 protein is fused to the 3′ region of HOXA9. Here, we show that retroviral-mediated enforced expression of the NUP98-HOXA9 fusion protein in cord blood–derived CD34+ cells confers a proliferative advantage in both cytokine-stimulated suspension cultures and stromal coculture. This advantage is reflected in the selective expansion of hematopoietic stem cells as measured in vitro by cobblestone area–forming cell assays and in vivo by competitive repopulation of nonobese diabetic/severe combined immunodeficient mice. NUP98-HOXA9 expression inhibited erythroid progenitor differentiation and delayed neutrophil maturation in transduced progenitors but strongly enhanced their serial replating efficiency. Analysis of the transcriptosome of transduced cells revealed up-regulation of several homeobox genes of the A and B cluster as well as of Meis1 and Pim-1 and down-modulation of globin genes and of CAAT/enhancer binding protein α. The latter gene, when coexpressed with NUP98-HOXA9, reversed the enhanced proliferation of transduced CD34+ cells. Unlike HOXA9, the NUP98-HOXA9 fusion was protected from ubiquitination mediated by Cullin-4A and subsequent proteasome-dependent degradation. The resulting protein stabilization may contribute to the leukemogenic activity of the fusion protein. (Cancer Res 2006; 66(24): 11781-91)
Non-coding RNAs in Cardiac Remodeling and Heart Failure
Authors: Regalla Kumarswamy, Thomas Thum
Journal: Circulation Research (2013)

Heart failure is a leading cause of death in industrialized nations especially in an aging population. The recent improvements in cardiac revascularization therapy reduced death rates because of myocardial infarction but steadily increased the number of individuals developing cardiac remodeling and heart failure in the future. Conceptual novel approaches entering the clinics to treat cardiac remodeling and heart failure remain scarce. MicroRNAs emerged as powerful and dynamic modifiers of cardiovascular diseases. In this review, the current approaches using microRNAs as novel diagnostic and therapeutic strategies for cardiac remodeling and heart failure are highlighted. Other gene regulatory mechanisms presented include long (>200 bp) noncoding RNAs that function as an additional regulatory machinery of the genome controlling both transcriptional and post-transcriptional events also in the cardiovascular system.
Spindle-Assembly Checkpoint and Gastrointestinal Cancer
Authors: Richarda M. de Voer, Nicoline Hoogerbrugge, Roland P. Kuiper
Journal: New England Journal of Medicine (2011)

To the Editor: Rio Frio et al. (Dec. 30 issue)1 report on a germline homozygous mutation in the spindle-assembly checkpoint gene BUB1B in a patient with a nonclassic form of the mosaic variegated aneuploidy syndrome, resulting in reduced expression, increased levels of constitutive aneuploidy, and multiple gastrointestinal neoplasms starting at 34 years of age. The spindle-assembly checkpoint complex, which controls proper chromosome segregation, is sensitive to gene dosage.2 Interestingly, we recently encountered a monoallelic deletion, approximately 1.75 Mb, encompassing another important spindle-assembly checkpoint component gene, BUB1, in a patient with a microsatellite-stable colon carcinoma at 37 years of age. Also, . . .
Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups
Authors: M. V. Madsen, P. C Gotzsche, A. Hrobjartsson
Journal: BMJ (2009)

<b>Objectives</b> To study the analgesic effect of acupuncture and placebo acupuncture and to explore whether the type of the placebo acupuncture is associated with the estimated effect of acupuncture. <b>Design</b> Systematic review and meta-analysis of three armed randomised clinical trials. <b>Data sources</b> Cochrane Library, Medline, Embase, Biological Abstracts, and PsycLIT. <b>Data extraction and analysis</b> Standardised mean differences from each trial were used to estimate the effect of acupuncture and placebo acupuncture. The different types of placebo acupuncture were ranked from 1 to 5 according to assessment of the possibility of a physiological effect, and this ranking was meta-regressed with the effect of acupuncture. <b>Data synthesis</b> Thirteen trials (3025 patients) involving a variety of pain conditions were eligible. The allocation of patients was adequately concealed in eight trials. The clinicians managing the acupuncture and placebo acupuncture treatments were not blinded in any of the trials. One clearly outlying trial (70 patients) was excluded. A small difference was found between acupuncture and placebo acupuncture: standardised mean difference −0.17 (95% confidence interval −0.26 to −0.08), corresponding to 4 mm (2 mm to 6 mm) on a 100 mm visual analogue scale. No statistically significant heterogeneity was present (P=0.10, I<sup>2</sup>=36%). A moderate difference was found between placebo acupuncture and no acupuncture: standardised mean difference −0.42 (−0.60 to −0.23). However, considerable heterogeneity (P&lt;0.001, I<sup>2</sup>=66%) was also found, as large trials reported both small and large effects of placebo. No association was detected between the type of placebo acupuncture and the effect of acupuncture (P=0.60). <b>Conclusions</b> A small analgesic effect of acupuncture was found, which seems to lack clinical relevance and cannot be clearly distinguished from bias. Whether needling at acupuncture points, or at any site, reduces pain independently of the psychological impact of the treatment ritual is unclear.
Introduction
Authors: D J Hendrick, D M Mitchell
Journal: Thorax (1998)

Since this is an historic meeting which will address one of the most important clinical issues in the field of sleep medicine, it is appropriate to examine how we arrived at this moment. Accordingly, I will present a brief review of the history of sleep medicine. I have addressed this topic on several previous occasions.1-3 In my view the history of sleep medicine can be divided into five clearly demarcated phases. These are listed in table 1.

View this table:

Table 1 
History of sleep medicine



I have designated the first phase, to some extent with tongue in cheek, as “prehistoric”. This reflects the relative lack of scientific experimentation involving sleep over the first half of the 20th century and before. The subject of dreams and dream interpretation probably received the most attention. A great deal of the early sleep literature reported observations on sleep habits and sleep characteristics in the service of comparing and contrasting the data reciprocally to data describing the waking state. During this “prehistoric” period nearly every biomedical scientist assumed that sleep occurred when sensory stimulation continuously bombarding the brain during the day was rendered insufficient to maintain a waking level of brain activity by the occurrence of the darkness and silence of night.

It seems reasonable that this perspective, often called the “passive process theory”, would have made the study of sleep seem relatively uninteresting. The notion that sleep was the brain “turned off” led to the erroneous conclusion that sleep could be regarded as an entirely homogenous state, and that a single observation could be generalised to the entire sleep period. Finally, there was no tradition of staying up at night to carry out scientific research except, of course, for astronomy.

There are some “prehistoric” scientific landmarks that are worth noting but which occurred far too early …