tbuckley/cabot-search huggingface dataset:
Trends in hospital admissions for pulmonary embolism in Spain from 2002 to 2011
Authors: Javier de Miguel-Díez, Rodrigo Jiménez-García, David Jiménez, Manuel Monreal, Ricardo Guijarro, Remedios Otero, Valentín Hernández-Barrera, Javier Trujillo-Santos, Ana López de Andrés, Pilar Carrasco-Garrido
Journal: European Respiratory Journal (2014)

The aim of our study was to analyse changes in the incidence, diagnostic procedures, comorbidity, length of hospital stay, costs and in-hospital mortality of patients hospitalised for pulmonary embolism in Spain over a 10-year period. We included all patients who were hospitalised for pulmonary embolism (ICD-9-CM codes 415.11 and 415.19) as the primary diagnosis between 2002 and 2011. Data were collected from the National Hospital Discharge Database, covering the entire Spanish population. 115 671 patients were admitted. The overall crude incidence increased from 20.44 per 100 000 inhabitants in 2002 to 32.69 in 2011 (p<0.05). In 2002, 13.3% of patients had a Charlson comorbidity index>2, and in 2011 the prevalence increased to 20.8% (p<0.05). Mean length of hospital stay was 12.7 days in 2002 and decreased to 9.99 in 2011 (p<0.05). During the study period, mean cost per patient increased from €3915 to €4372 (p<0.05). In-hospital mortality decreased from 12.9% in 2002 to 8.32% in 2011 (p<0.05). The increase in the use of computed tomographic pulmonary angiography over time was associated with increased incidence and lower mortality. Our results revealed an increase in the incidence of hospitalised pulmonary embolism patients from 2002 to 2011 with concomitant increase in comorbidities and cost. However, length of hospital stay and in-hospital mortality decreased.
Serum samples of patients with rheumatoid arthritis contain a specific autoantibody to "denatured" aldolase A in the osteoblast-like cell line, MG-63
Authors: F. Ukaji, I. Kitajima, T. Kubo, C. Shimizu, T. Nakajima, I. Maruyama
Journal: Annals of the Rheumatic Diseases (1999)

To identify rheumatoid arthritis (RA) specific autoantibody and its antigen in the human osteoblast-like cell line, MG-63.MG-63 cell extract was subjected to western blotting by using RA and normal serum samples as probes. The autoantigen was purified and its N-terminal sequence was determined by automated Edman degradation. The reactivity of denatured aldolase A was evaluated by immunoblotting. Screening by enzyme linked immunosorbent assay (ELISA) using the autoantibody was performed.40 kDa protein was found only in the RA serum samples and it was identified as aldolase A. A polyclonal antibody for rabbit muscle aldolase A bound to the 40 kDa protein and reacted in preference with the denatured enzyme. Using ELISA for denatured rabbit aldolase A, the autoantibody was found in approximately 10% of RA patients, whereas it was not found in the other arthropathy and healthy adults.This 40 kDa anti-aldolase A autoantibody, which was identified only in serum samples of RA patients with severe bone erosion, could be related to a certain event that induces RA specific joint destructions.
Defining a Candidate Lung Cancer Gene
Authors: Frederic J. Kaye
Journal: JNCI Journal of the National Cancer Institute (2008)

In this issue of the Journal, Yuan et al. ( 1 ) tested 50 uncharacterized genes that their laboratory had previously shown to be differentially expressed in squamous cell lung tumors as compared with normal bronchial epithelial cells ( 2 – 5 ) for foci formation following transfection of each gene into NIH3T3 cells using antibiotic selection. They identified one gene with foci formation, designated OLC1, and subsequently demonstrated elevated levels of OLC1 by immunoblot analysis in four lung tumor cell lines as compared with several immortalized lung lines. In addition, the authors performed immunohistochemistry (IHC) on 537 primary archival lung cancer samples embedded on tissue arrays and detected overexpression of OLC1 in 83.4% of lung tumors as compared with 23.3% of adjacent normal tissues. Subset analysis of the IHC staining patterns against different clinical and demographic features did not show statistically significant associations, except for increased OLC1 staining in samples from smokers (77.1%) as compared with nonsmokers (45.8%). To address possible mechanisms for OLC1 overexpression, the authors detected a two- or threefold increase in DNA gene copy number in several primary tumor samples, but no high copy number clusters of gene amplification were reported. Finally, the authors noted that constitutive ectopic expression of OLC1 in NIH3T3 cells, but not in immortalized MBE bronchial epithelial cells, was associated with enhanced colony growth in soft agar and in tumor xenograft formation in nude mice. Conversely, siRNA silencing of OLC1 in two lung tumor cell lines was convincingly associated with increased parameters of apoptosis and reduced colony growth. In summary, the authors conclude that their data strongly suggest that OLC1 is a newly discovered candidate oncogene implicated in the development of human lung cancer. How should we now place these data in perspective with the growing number of etiologic lung cancer gene targets? First of all, the identifi cation of an “uncharacterized” gene product that is highly conserved from human to yeast is always exciting for the bench researcher because it promises great rewards in unraveling (perhaps) a new signaling pathway that evolution has defi ned as essential for cellular survival and reproduction. However, what is the evidence that it functions as an etiologic mammalian cancer gene and, for that matter, how can one defi ne a bona fi de cancer gene? To some extent, this question is both semantic (as hundreds of genes can impact or respond to all cancer gene pathways) and practical (limited resources to pursue candidate gene targets for
Assessing the Presence of Circulating Tumor Cells in Breast Cancer Patients Using Multiplex Reverse Transcription Polymerase Chain Reaction and Specific Primers for Mammaglobin, Pthrp and Ck19
Authors: M. Skondra, E. Gkioka, I.D. Kostakis, A. Tzovaras, S. Karageorgopoulou, D.G. Pectasides, M. Koutsilieris
Journal: Annals of Oncology (2014)
The microtubule-associated protein DCAMKL1 regulates osteoblast function via repression of Runx2
Authors: Weiguo Zou, Matthew B. Greenblatt, Nicholas Brady, Sutada Lotinun, Bo Zhai, Heather de Rivera, Anju Singh, Jun Sun, Steven P. Gygi, Roland Baron, Laurie H. Glimcher, Dallas C. Jones
Journal: The Journal of Experimental Medicine (2013)

Osteoblasts are responsible for the formation and mineralization of the skeleton. To identify novel regulators of osteoblast differentiation, we conducted an unbiased forward genetic screen using a lentiviral-based shRNA library. This functional genomics analysis led to the identification of the microtubule-associated protein DCAMKL1 (Doublecortin-like and CAM kinase–like 1) as a novel regulator of osteogenesis. Mice with a targeted disruption of Dcamkl1 displayed elevated bone mass secondary to increased bone formation by osteoblasts. Molecular experiments demonstrated that DCAMKL1 represses osteoblast activation by antagonizing Runx2, the master transcription factor in osteoblasts. Key elements of the cleidocranial dysplasia phenotype observed in Runx2+/− mice are reversed by the introduction of a Dcamkl1-null allele. Our results establish a genetic linkage between these two proteins in vivo and demonstrate that DCAMKL1 is a physiologically relevant regulator of anabolic bone formation.
Molecular Pathways: Inhibiting Steroid Biosynthesis in Prostate Cancer
Authors: Roberta Ferraldeschi, Nima Sharifi, Richard J. Auchus, Gerhardt Attard
Journal: Clinical Cancer Research (2013)

Abstract A significant proportion of castration-resistant prostate cancers (CRPC) remains driven by ligand activation of the androgen receptor. Although the testes are the primary source of testosterone, testosterone can also be produced from peripheral conversion of adrenal sex hormone precursors DHEA and androstenedione in the prostate and other tissues. CYP17A1 catalyzes two essential reactions in the production of DHEA and androstenedione: the hydroxylation (hydroxylase activity) and the subsequent cleavage of the C17-20 side chain (lyase activity). Potent and selective inhibition of CYP17A1 by abiraterone depletes residual nongonadal androgens and is an effective treatment for CRPC. Elucidation of the mechanisms that underlie resistance to abiraterone will inform the development of novel therapeutic strategies post-abiraterone. Preclinical evidence that androgen biosynthesis in prostate cancer cells does not necessarily follow a single dominant pathway, and residual androgens or alternative ligands (including administered glucocorticoids) can reactivate androgen receptor signaling, supports cotargeting of more than one enzyme involved in steroidogenesis and combining a CYP17A1 inhibitor with an antiandrogen. Furthermore, given the drawbacks of 17α-hydroxylase inhibition, there is considerable interest in developing new CYP17A1 inhibitors that more specifically inhibit lyase activity and are therefore less likely to require glucocorticoid coadministration. Clin Cancer Res; 19(13); 3353–9. ©2013 AACR.
Discordance in Perceived Needs Between Patients and Physicians in Oncology Practice: A Nationwide Survey in Korea
Authors: Dong Wook Shin, So Young Kim, Juhee Cho, Robert W. Sanson-Fisher, Eliseo Guallar, Gyu Young Chai, Hak-Soon Kim, Bo Ram Park, Eun-Cheol Park, Jong-Hyock Park
Journal: Journal of Clinical Oncology (2011)

Identification of supportive care needs in patients with cancer is essential for planning appropriate interventions. We aimed to determine patient-physician concordance in perceived supportive care needs in cancer care and to explore the predictors and potential consequences of patient-physician concordance.A national, multicenter, cross-sectional survey of patient-physician dyads was performed, and 97 oncologists (participation rate, 86.5%) and 495 patients (participation rate, 87.4%) were included. A short form of the Comprehensive Needs Assessment Tool for Cancer Patients was independently administered to patients and their oncologists. Concordance and agreement rates between physicians and patients were calculated. Mixed logistic regression was used to identify predictors of concordance and to explore the association of concordance with patient satisfaction and trust in physicians.Physicians systematically underestimated patient needs and patient-physician concordance was generally poor, with weighted κ statistics ranging from 0.04 to 0.15 for individual items and Spearman's ρ coefficients ranging from 0.11 to 0.21 for questionnaire domains. Length of experience as oncologist was the only significant predictor of concordance (adjusted odds ratio for overall concordance [aOR] = 2.09; 95% CI, 1.02 to 4.31). Concordance was not significantly associated with overall patient satisfaction (aOR = 1.24; 95% CI, 0.74 to 2.07) or trust in physician (aOR = 1.17; 95% CI, 0.76 to 1.81).Our findings revealed significant underestimation of patient needs and poor concordance between patients and physicians in assessing perceived needs of supportive care. The clinical implications of this discordance warrant further investigation.
Polymorphisms in the tumour necrosis factor gene are not associated with severity of inflammatory polyarthritis
Authors: A Barton
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Tumour necrosis factor alpha (TNFα) is a powerful inflammatory mediator in rheumatoid and other types of inflammatory arthritis. Polymorphisms within the TNFα gene have previously been investigated to determine their role in the aetiopathogenesis of rheumatoid arthritis (RA), but it is unclear whether reported associations are with susceptibility to, or severity of, disease. <b>Objective:</b> To examine the association between both individual TNFα single nucleotide polymorphisms (SNPs) and haplotypes with the development and severity of erosions by 5 years in patients with inflammatory polyarthritis (IP). <b>Methods:</b> 438 patients from the Norfolk Arthritis Register observational inception cohort of patients with IP were <i>x</i> rayed 5 years after disease onset. They were genotyped for nine SNPs mapping to the TNFα gene, using a SNaPshot primer extension assay. Haplotypes were constructed in patients with IP, who were compared for the presence and extent of erosions at 5 years. <b>Results:</b> No association between individual TNFα SNPs or haplotypes in the patients who developed erosions at 5 years compared with those who remained non-erosive was found. Restricting analysis to patients who satisfied ACR criteria for RA by 5 years did not affect the conclusions. <b>Conclusion:</b> The TNFα gene does not seem to be associated with severity as assessed by erosive outcome at 5 years in patients with IP.
Analysis of K-ras gene mutations in malignant and nonmalignant endobronchial tissue obtained by fiberoptic bronchoscopy.
Authors: N C Clements, M A Nelson, J A Wymer, C Savage, M Aguirre, H Garewal
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Using polymerase chain reaction DNA amplification, we identified K-ras oncogene mutations in bronchial biopsies obtained from patients undergoing bronchoscopy for clinical indications. We hypothesized that these mutations would be found in a field encompassing malignant and nonmalignant tissues in patients with pulmonary carcinomas, and also possibly in tissue from some patients who smoked but did not have pulmonary malignancy. We found K-ras mutations in endobronchial biopsies from nine of 22 patients (41%) with carcinoma of the lung. In five of these patients, mutations were found in both malignant and nonmalignant specimens. In two instances, mutations were found only in the neoplastic tissue, and in two cases mutations were present only in the nonmalignant tissue. Furthermore, we identified two patients with K-ras mutations among seven patients in whom no clinical malignancy was apparent. Our data suggest that some oncogene activations may occur over a broad area in smokers with and without malignancy, and they imply that K-ras mutations may serve as surrogate markers for malignant potential.
Chromosome 20p11 gains are associated with liver-specific metastasis in patients with colorectal cancer
Authors: Leonie J M Mekenkamp, Josien C Haan, Miriam Koopman, M Elisa Vink-Börger, Daniëlle Israeli, Steven Teerenstra, Bauke Ylstra, Gerrit A Meijer, Cornelis J A Punt, Iris D Nagtegaal
Journal: Gut (2012)

<h3>Objective</h3> Metastatic colorectal cancer (CRC) cells have a selective preference for certain target organs that cannot be explained by circulatory patterns alone. This study aimed to identify clinicopathological features and chromosomal aberrations of primary tumours associated with organ-specific CRC metastasis. <h3>Design</h3> Clinicopathological features were investigated in patients with CRC who had exclusively hepatic (n=182) versus exclusively extrahepatic (n=139) metastases. A total of 139 primary tumours of patients with hepatic (n=85) and extrahepatic metastases (n=54) were screened for chromosomal aberrations by microarray-based comparative genomic hybridisation, and the findings were validated in an independent set of 80 primary tumours. A publicly available database was used to correlate chromosomal aberrations with gene expression. Protein expression was evaluated by immunohistochemistry on tissue microarrays. <h3>Results</h3> Patients with hepatic metastases were significantly more often male (71% vs 53% p=0.002), more often had abnormal lactate dehydrogenase activity (37% vs 14% p&lt;0.0001), exhibited primary tumour localisation in the colon (52% vs 40% p=0.03) and had synchronous onset of metastases (70% vs 19% p&lt;0.0001). Primary tumours of patients with hepatic metastases were more commonly T3 tumours (79% vs 63% p=0.006) and less commonly of mucinous histology (5% vs 16% p=0.02). Gain of 20p11 was more often observed in patients with hepatic metastases (p&lt;0.05), which was confirmed in an independent dataset (p&lt;0.05; false discovery rate &lt;0.05). Twelve genes mapping at 20p11 were significantly overexpressed as a consequence of 20p11 copy number gain. <i>C20orf3</i> showed the strongest correlation between RNA expression and DNA copy number. This was reflected in significantly higher protein expression in patients with hepatic metastases (59%; n=325) than in those with extrahepatic metastases (41%; n=256) (p=0.01). <h3>Conclusion</h3> <i>C20orf3</i> mapping at 20p11 is associated with hepatic-specific metastasis in patients with CRC. This gene is a candidate biomarker for liver metastases and may be of clinical value in early-stage CRC.
New Therapies for Castration-Resistant Prostate Cancer: Efficacy and Safety
Authors: Himisha Beltran, Tomasz M. Beer, Michael A. Carducci, Johann de Bono, Martin Gleave, Maha Hussain, William K. Kelly, Fred Saad, Cora Sternberg, Scott T. Tagawa, Ian F. Tannock
Journal: European Urology (2011)
Unusual cranial and abdominal computed tomographic (CT) scan appearances in a case of systemic lupus erythematosus (SLE).
Authors: M Boulter, A Brink, C Mathias, S Peart, J Stevens, G Stewart, R Unwin
Journal: Annals of the Rheumatic Diseases (1987)

A 35 year old woman presented with headache and fever. Computed brain tomography showed diffuse low attenuation in the cerebral white matter. Several months later, serological tests for systemic lupus erythematosus (SLE) became positive. In spite of immunosuppressive therapy she relapsed after six months of treatment, presenting with abdominal symptoms and signs. On this occasion an abdominal CT scan showed distended and oedematous loops of bowel attributed to an underlying vasculitis. This case illustrates novel CT scan appearances in two systems involved in SLE.
Natural Killer Cell–Mediated Lysis of Hepatoma Cells via Specific Induction of NKG2D Ligands by the Histone Deacetylase Inhibitor Sodium Valproate
Authors: Sorin Armeanu, Michael Bitzer, Ulrich M. Lauer, Sascha Venturelli, Anita Pathil, Matthias Krusch, Stephan Kaiser, Jürgen Jobst, Irina Smirnow, Annika Wagner, Alexander Steinle, Helmut R. Salih
Journal: Cancer Research (2005)

Abstract Natural killer (NK) cells as components of the innate immunity substantially contribute to antitumor immune responses. However, the tumor-associated ligands engaging activating NK cell receptors are largely unknown. An exception are the MHC class I chain-related molecules MICA and MICB and the UL16-binding proteins (ULBP) which bind to the activating immunoreceptor NKG2D expressed on cytotoxic lymphocytes. A therapeutic induction of NKG2D ligands that primes cancer cells for NK cell lysis has not yet been achieved. By microarray studies, we found evidence that treatment of human hepatocellular carcinoma cells with the histone deacetylase inhibitor (HDAC-I) sodium valproate (VPA) mediates recognition of cancer cells by cytotoxic lymphocytes via NKG2D. VPA induced transcription of MICA and MICB in hepatocellular carcinoma cells, leading to increased cell surface, soluble and total MIC protein expression. No significant changes in the expression of the NKG2D ligands ULBP1-3 were observed. The induction of MIC molecules increased lysis of hepatocellular carcinoma cells by NK cells which was abolished by addition of a blocking NKG2D antibody. Importantly, in primary human hepatocytes, VPA treatment did not induce MIC protein expression. Taken together, our data show that the HDAC-I VPA mediates specific priming of malignant cells for innate immune effector mechanisms. These results suggest the clinical evaluation of HDAC-I in solid tumors such as hepatocellular carcinoma, especially in combination with immunotherapy approaches employing adoptive NK cell transfer.
Liver alkaline phosphatase: A missing link between choleresis and biliary inflammation
Authors: Raoul Poupon
Journal: Hepatology (2015)

Several lines of evidence show that serum alkaline phosphatase (AP) is not only a signpost of cholestasis but also a surrogate marker of the severity of primary biliary cirrhosis and primary sclerosing cholangitis. In the present opinion article, we review and discuss the putative role of liver AP in health and in cholestatic diseases. In inflammatory cholestatic conditions, loss of activity of liver AP (resulting from its relocation from canaliculi and the acidic milieu) might promote hyper‐adenosine triphosphate‐bilia, lipopolysaccharide overload, and subsequent exacerbation and perpetuation of inflammation. Drugs that can restore the polarity of hepatocytes and canalicular export of bile acids or act as bile alkalinity modifiers are predicted to exert anti‐inflammatory effects and to benefit both primary biliary cirrhosis and primary sclerosing cholangitis. Oral administration of intestinal AP could be a valid therapeutic intervention that deserves further study under experimental conditions as well as in human diseases. Overall, the key role of the liver microenvironment that might shape the different facets of the inflammatory processes in fibrosing cholangiopathies is highlighted. (H epatology 2015;61:2080–2090)
Dehydroepiandrosterone reverses chronic hypoxia/reoxygenation-induced right ventricular dysfunction in rats
Authors: Eric Dumas de La Roque, Nadège Bellance, Rodrigue Rossignol, Hugues Begueret, Marie Billaud, Pierre Dos Santos, Thomas Ducret, Roger Marthan, Diana Dahan, David Ramos-Barbón, Óscar Amor-Carro, Jean-Pierre Savineau, Michael Fayon
Journal: European Respiratory Journal (2012)

Dehydroepiandrosterone (DHEA) prevents chronic hypoxia-induced pulmonary hypertension and associated right ventricle dysfunction in rats. In this animal model, reoxygenation following hypoxia reverses pulmonary hypertension but not right ventricle dysfunction. We thus studied the effect of DHEA on the right ventricle after reoxygenation, i.e. after a normoxic recovery phase secondary to chronic hypoxia in rats. Right ventricle function was assessed in vivo by Doppler echocardiography and in vitro by the isolated perfused heart technique in three groups of animals: control, recovery (21 days of hypoxia followed by 21 days of normoxia) and recovery DHEA (30 mg · kg(-1) every 2 days during the recovery phase). Right ventricle tissue was assessed by optical and electron microscopy. DHEA abolished right ventricle diastolic dysfunction, as the echographic E wave remained close to that of controls (mean ± SD 76.5 ± 2.4 and 79.7 ± 1.7 cm · s(-1), respectively), whereas it was diminished to 40.3 ± 3.7 in the recovery group. DHEA also abolished right ventricle systolic dysfunction, as shown by the inhibition of the increase in the slope of the pressure-volume curve in isolated heart. The DHEA effect was related to cardiac myocytes proliferation. In conclusion, DHEA prevents right ventricle dysfunction in this animal model by preventing cardiomyocyte alteration.
Stages of Treatment in the Case of a Diaper-Wearing Seventeen-Year-Old Male
Authors: FRANK A. DINELLO
Journal: American Journal of Psychiatry (1967)

A case is reported in which the presenting symptoms appeared to be a rather bizarre perversion and severe regression but with no evidence of psychosis. The treatment was interpretive in nature and was aimed at understanding the meaning of the patient's defenses in relation to his fears of growing up. The different maturational stages reached during treatment and the new problems and coping methods of each stage are indicated. In many ways the treatment was similar to that of any adolescent who experiences difficulty in adjusting to physical maturation. In this case the physical maturation was medically accelerated, which stimulated unusually severe defense mechanisms.