tbuckley/cabot-search huggingface dataset:
Translocation of the atrial septum
Authors: C. R. C. Wyndham
Journal: Thorax (1970)

Translocation of the atrial septum to the left of the mitral valve is a congenital anomaly: the author has not found a similar case previously reported in the English literature. The curious anomaly described here was associated with deformed mitral and tricuspid valves, a postero-inferior atrial septal defect, a persistent left superior vena cava, a hypoplastic aorta, and a short innominate artery. The patient lived to a remarkable age.
Tissue factor in tumor microenvironment: a systematic review
Authors: Xiao Han, Bo Guo, Yongsheng Li, Bo Zhu
Journal: Journal of Hematology & Oncology (2014)

The aberrant hemostasis is a common manifestation of cancer, and venous thromboembolism (VTE) is the second leading cause of cancer patients' mortality. Tissue factor (TF), comprising of a 47-kDa transmembrane protein that presents in subendothelial tissues and leukocytes and a soluble isoform, have distinct roles in the initiation of extrinsic coagulation cascade and thrombosis. Laboratory and clinical evidence showed the deviant expression of TF in several cancer systems and its tumor-promoting effects. TF contributes to myeloid cell recruitment in tumor stroma, thereby remodeling of tumor microenvironment. Additionally, the number of TF-positive-microparticles (TF+MP) from tumor origins correlates with the VTE rates in cancer patients. In this review, we summarize our current understanding of the TF regulation and roles in tumor progression and clinical complications.
The Failure of STAT6-deficient Mice to Develop Airway Eosinophilia and Airway Hyperresponsiveness Is Overcome by Interleukin-5
Authors: ADRIAN TOMKINSON, ARIHIKO KANEHIRO, NATHAN RABINOVITCH, ANTHONY JOETHAM, GRZEGORZ CIESLEWICZ, ERWIN W. GELFAND
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

While signal transducer and activator of transcription protein 6 (STAT6) is important in interleukin-4 (IL-4)-induced commitment of CD4(+) T cells to the T helper cell, type 2 (Th2) phenotype and IgE isotype switching in B cells, its role in other IL-4-mediated events and their impact upon the allergic response is less evident. In the present study we demonstrate the critical role of STAT6 in the development of allergic airway eosinophilia and airway hyperresponsiveness (AHR) after allergen sensitization and challenge. STAT6-deficient (STAT6-/-) mice did not develop a Th2 cytokine response or an allergen-specific IgE response. Further, STAT6-/- mice had a reduced constitutive and allergen-induced expression of CD23 as well as lower mucus production in the airway epithelium. Critically, we show that IL-5 alone can reconstitute airway eosinophilia and AHR in sensitized and challenged STAT6-/- mice. This emphasizes the essential nature of the IL-4-dependent signaling of T cells to the Th2 phenotype and secretion of IL-5, resulting in the airway eosinophilia and AHR. These observations underscore the importance of targeting this pathway in new antiallergic asthma drug development.
Lipopolysaccharide-induced Diaphragmatic Contractile Dysfunction in Mice Lacking the Inducible Nitric Oxide Synthase
Authors: ALAIN S. COMTOIS, QASIM EL-DWAIRI, VICTOR E. LAUBACH, SABAH N. A. HUSSAIN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The goal of this study was to evaluate the importance of the inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced diaphragmatic contractile dysfunction. Many investigators have proposed that iNOS induction in the ventilatory and limb muscles of animals injected with Escherichia coli LPS leads to impaired muscle contractility and increased fatigability. We tested this proposal by examining wild-type mice and iNOS-deficient (iNOS knockout) mice. Both types of mice were injected with either saline (control) or E. coli LPS and killed after 12 h. Diaphragm nitric oxide synthase (NOS) activity, NOS expression, and muscle contractility were assessed with l-citrulline assay, immunoblotting, and in vitro bath preparation, respectively. LPS injection in wild-type mice induced iNOS protein expression and augmented total diaphragmatic NOS activity, which coincided with impaired muscle force generated at frequencies higher than 30 Hz. In iNOS knockout mice, injection of LPS augmented constitutive muscle NOS activity, upregulated the expression of the neuronal NOS (nNOS), but elicited a significantly greater decline in force generated in response to high frequency of stimulation compared with wild-type animals. We conclude that iNOS may play a protective role in attenuating the inhibitory influence of LPS on muscle contractility.
Presence of paf-acether in rheumatic diseases.
Authors: P Hilliquin, C.J Menkes, S Laoussadi, J Benveniste, B Arnoux
Journal: Annals of the Rheumatic Diseases (1992)

Paf-acether (paf) is a naturally occurring phospholipid involved in inflammatory processes. The presence of paf, its precursor lyso paf, and lipo-paf has been determined in blood and synovial fluid from 13 patients with rheumatoid arthritis (RA), 11 with spondylarthropathies, eight with other inflammatory rheumatisms, 13 with chondrocalcinosis, 15 with osteoarthritis, and also in blood from nine healthy subjects. Paf and lipo-paf were measured by rabbit platelet aggregation after isolation by high performance liquid chromatography, whereas lyso paf was first chemically acetylated to give paf. Lipo-paf in blood was higher in patients than in controls; lipo-paf concentrations in blood and in synovial fluid were significantly higher in rheumatoid arthritis than in osteoarthritis and chondrocalcinosis. By contrast, paf and lyso paf reached their lower values in rheumatoid arthritis. The amounts of lipid mediators were not correlated with biological parameters of inflammation. Lipo-paf, which is considered as a storage form of paf, may be the important form of paf in active inflammatory rheumatism.
PROTEASOME INHIBITION IN MULTIPLE MYELOMA: Therapeutic Implication
Authors: Dharminder Chauhan, Teru Hideshima, Kenneth C. Anderson
Journal: The Annual Review of Pharmacology and Toxicology (2005)

Normal cellular functioning requires processing of proteins regulating cell cycle, growth, and apoptosis. The ubiquitin-proteasome pathway (UBP) modulates intracellular protein degradation. Specifically, the 26S proteasome is a multienzyme protease that degrades misfolded or redundant proteins; conversely, blockade of the proteasomal degradation pathways results in accumulation of unwanted proteins and cell death. Because cancer cells are more highly proliferative than normal cells, their rate of protein translation and degradation is also higher. This notion led to the development of proteasome inhibitors as therapeutics in cancer. The FDA recently approved the first proteasome inhibitor bortezomib (Velcade), formerly known as PS-341, for the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). Ongoing studies are examining other novel proteasome inhibitors, in addition to bortezomib, for the treatment of MM and other cancers.
Attenuated Myocardial Vasodilator Response in Patients With Hypertensive Hypertrophy Revealed by Oxygenation-Dependent Magnetic Resonance Imaging
Authors: Garth M. Beache, Daniel A. Herzka, Jerrold L. Boxerman, Wendy S. Post, Sandeep N. Gupta, Anthony Z. Faranesh, Meiyappan Solaiyappan, Paul A. Bottomley, James L. Weiss, Edward P. Shapiro, Martha N. Hill
Journal: Circulation (2001)

Background Oxygen (O 2 ) homeostasis is central to myocardial tissue functioning, and increased O 2 demand is thought to be satisfied by a vasodilatory mechanism that results in increased blood and O 2 delivery. We applied blood oxygenation level–dependent (BOLD) MRI in conjunction with vasodilatory stress to index the ability to augment intramyocardial oxygenation in hypertensive hypertrophy, the primary cause of heart failure. Methods and Results Nine healthy controls and 10 hypertensive subjects with moderate-to-severe hypertrophy underwent imaging on a 1.5 T clinical scanner. The dipyridamole-induced change in the apparent transverse relaxation rate, R2*, which correlates with hemoglobin oxygenation, was −5.4±2.2 s −1 (95% CI, −4.0 to −6.8 s −1 ) in controls compared with −1.7±1.4 s −1 (95% CI, −0.8 to −2.6 s −1 ) in hypertensive patients ( P =0.0003). Conclusions Patients with hypertensive hypertrophy demonstrate an impaired ability to increase intramyocardial oxygenation during vasodilatory stress, as indexed by BOLD MRI. The capacity to image vascular function with BOLD MRI may advance the understanding of the development of ventricular dysfunction in hypertension.
High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients
Authors: J Lacronique, D Renon, D Georges, M Henry-Amar, J Marsac
Journal: European Respiratory Journal (1991)

One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.
A randomized phase II trial of capecitabine and two different schedules of irinotecan in first-line treatment of metastatic colorectal cancer: efficacy, quality-of-life and toxicity
Authors: M.M. Borner, J. Bernhard, D. Dietrich, R. Popescu, M. Wernli, P. Saletti, D. Rauch, R. Herrmann, D. Koeberle, H. Honegger, P. Brauchli, D. Lanz, A.D. Roth
Journal: Annals of Oncology (2005)
Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia
Authors: Giuseppe Saglio, Dong-Wook Kim, Surapol Issaragrisil, Philipp le Coutre, Gabriel Etienne, Clarisse Lobo, Ricardo Pasquini, Richard E. Clark, Andreas Hochhaus, Timothy P. Hughes, Neil Gallagher, Albert Hoenekopp, Mei Dong, Ariful Haque, Richard A. Larson, Hagop M. Kantarjian
Journal: New England Journal of Medicine (2010)

Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase.In this phase 3, randomized, open-label, multicenter study, we assigned 846 patients with chronic-phase Philadelphia chromosome-positive CML in a 1:1:1 ratio to receive nilotinib (at a dose of either 300 mg or 400 mg twice daily) or imatinib (at a dose of 400 mg once daily). The primary end point was the rate of major molecular response at 12 months.At 12 months, the rates of major molecular response for nilotinib (44% for the 300-mg dose and 43% for the 400-mg dose) were nearly twice that for imatinib (22%) (P<0.001 for both comparisons). The rates of complete cytogenetic response by 12 months were significantly higher for nilotinib (80% for the 300-mg dose and 78% for the 400-mg dose) than for imatinib (65%) (P<0.001 for both comparisons). Patients receiving either the 300-mg dose or the 400-mg dose of nilotinib twice daily had a significant improvement in the time to progression to the accelerated phase or blast crisis, as compared with those receiving imatinib (P=0.01 and P=0.004, respectively). No patient with progression to the accelerated phase or blast crisis had a major molecular response. Gastrointestinal and fluid-retention events were more frequent among patients receiving imatinib, whereas dermatologic events and headache were more frequent in those receiving nilotinib. Discontinuations due to aminotransferase and bilirubin elevations were low in all three study groups.Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML. (ClinicalTrials.gov number, NCT00471497.)
Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial
Authors: Rebecca Aft, Michael Naughton, Kathryn Trinkaus, Mark Watson, Lourdes Ylagan, Mariana Chavez-MacGregor, Jing Zhai, Sacha Kuo, William Shannon, Kathryn Diemer, Virginia Herrmann, Jill Dietz, Amjad Ali, Matthew Ellis, Peter Weiss, Timothy Eberlein, Cynthia Ma, Paula M Fracasso, Imran Zoberi, Marie Taylor, William Gillanders, Timothy Pluard, Joanne Mortimer, Katherine Weilbaecher
Journal: The Lancet Oncology (2010)
Ultrasonography versus Computed Tomography for Suspected Nephrolithiasis
Authors: Rebecca Smith-Bindman, Chandra Aubin, John Bailitz, Rimon N. Bengiamin, Carlos A. Camargo, Jill Corbo, Anthony J. Dean, Ruth B. Goldstein, Richard T. Griffey, Gregory D. Jay, Tarina L. Kang, Dana R. Kriesel, O. John Ma, Michael Mallin, William Manson, Joy Melnikow, Diana L. Miglioretti, Sara K. Miller, Lisa D. Mills, James R. Miner, Michelle Moghadassi, Vicki E. Noble, Gregory M. Press, Marshall L. Stoller, Victoria E. Valencia, Jessica Wang, Ralph C. Wang, Steven R. Cummings
Journal: New England Journal of Medicine (2014)

There is a lack of consensus about whether the initial imaging method for patients with suspected nephrolithiasis should be computed tomography (CT) or ultrasonography.In this multicenter, pragmatic, comparative effectiveness trial, we randomly assigned patients 18 to 76 years of age who presented to the emergency department with suspected nephrolithiasis to undergo initial diagnostic ultrasonography performed by an emergency physician (point-of-care ultrasonography), ultrasonography performed by a radiologist (radiology ultrasonography), or abdominal CT. Subsequent management, including additional imaging, was at the discretion of the physician. We compared the three groups with respect to the 30-day incidence of high-risk diagnoses with complications that could be related to missed or delayed diagnosis and the 6-month cumulative radiation exposure. Secondary outcomes were serious adverse events, related serious adverse events (deemed attributable to study participation), pain (assessed on an 11-point visual-analogue scale, with higher scores indicating more severe pain), return emergency department visits, hospitalizations, and diagnostic accuracy.A total of 2759 patients underwent randomization: 908 to point-of-care ultrasonography, 893 to radiology ultrasonography, and 958 to CT. The incidence of high-risk diagnoses with complications in the first 30 days was low (0.4%) and did not vary according to imaging method. The mean 6-month cumulative radiation exposure was significantly lower in the ultrasonography groups than in the CT group (P<0.001). Serious adverse events occurred in 12.4% of the patients assigned to point-of-care ultrasonography, 10.8% of those assigned to radiology ultrasonography, and 11.2% of those assigned to CT (P=0.50). Related adverse events were infrequent (incidence, 0.4%) and similar across groups. By 7 days, the average pain score was 2.0 in each group (P=0.84). Return emergency department visits, hospitalizations, and diagnostic accuracy did not differ significantly among the groups.Initial ultrasonography was associated with lower cumulative radiation exposure than initial CT, without significant differences in high-risk diagnoses with complications, serious adverse events, pain scores, return emergency department visits, or hospitalizations. (Funded by the Agency for Healthcare Research and Quality.).
Ochratoxin A Carcinogenesis in the (C57BL/6J × C3H)F&lt;sub&gt;1&lt;/sub&gt; Mouse&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: A M Bendele, W W Carlton, P Krogh, E B Lillehoj
Journal: JNCI Journal of the National Cancer Institute (1985)

The potential carcinogenic effects of the mycotoxin ochratoxin A [(OA); CAS: 303-47-9] were assessed in a 24-month feeding study in male and female (C57BL/6J X C3H)F1 (B6C3F1) mice. The mice were assigned to 3 groups of 50 males and 50 females each; group 1 mice were the controls, group 2 mice were fed 1 ppm OA, and group 3 mice were fed 40 ppm OA. Renal neoplasms, both carcinomas and adenomas, were found only in male mice of the 40-ppm dose group. Fourteen of 49 animals that survived at least 20 months had neoplasms morphologically consistent with renal carcinoma. Renal adenomas were present in some of these mice and in other 40-ppm-group males, making a total of 26 mice with renal adenomas. All male mice of the 40-ppm dose group had nephropathy characterized by varying degrees of renal tubular dilation, attenuation and hyperplasia of lining epithelium, and proliferation of regenerative tubules. Females of the 40-ppm dose group had similar but less severe renal changes but no carcinomas or adenomas. Compound-related renal lesions were absent in the 1-ppm dose group. The incidence of hepatocellular neoplasms was slightly increased in male and female mice fed diets containing OA. These results indicate that OA is a renal carcinogen in male B6C3F1 mice and a hepatic carcinogen in female mice of this strain.
Plasma Level of B-Type Natriuretic Peptide as a Prognostic Marker After Acute Myocardial Infarction
Authors: Satoru Suzuki, Michihiro Yoshimura, Masafumi Nakayama, Yuji Mizuno, Eisaku Harada, Teruhiko Ito, Shota Nakamura, Koji Abe, Megumi Yamamuro, Tomohiro Sakamoto, Yoshihiko Saito, Kazuwa Nakao, Hirofumi Yasue, Hisao Ogawa
Journal: Circulation (2004)

Background— Circulating levels of B-type natriuretic peptide (BNP), a cardiac hormone, reflect the severity of cardiac dysfunction. Because the plasma BNP level changes dramatically during the period after the onset of acute myocardial infarction (AMI), identification of a suitable sampling time is problematic. There have been several reports indicating that the plasma BNP level obtained in the acute phase of AMI can be used as a prognostic marker. We examined whether the plasma BNP level measured 3 to 4 weeks after the onset of AMI represents a reliable prognostic marker for patients with AMI. Methods and Results— We analyzed 145 consecutive patients with AMI. Plasma BNP levels were measured during the 3 to 4 weeks after onset of AMI. Of those patients, 23 experienced fatal cardiac events during this study. The mean follow-up period was 58.6 months. Log BNP, left ventricular end-diastolic pressure, and pulmonary vascular resistance were all significantly higher in the cardiac death group, and there were more men and more patients with a history of heart failure in the cardiac death group. A Cox proportional hazards model analysis showed that log BNP was an independent predictor of cardiac death. The survival rate was significantly higher in patients with log BNP &lt;2.26 (180 pg/mL) than in those with log BNP ≥2.26. Conclusions— The plasma BNP level obtained 3 to 4 weeks after the onset of AMI can be used as an independent predictor of cardiac death in patients with AMI.
Genetic Variants in miRNAs Predict Bladder Cancer Risk and Recurrence
Authors: Meilin Wang, Haiyan Chu, Pu Li, Lin Yuan, Guangbo Fu, Lan Ma, Danni Shi, Dongyan Zhong, Na Tong, Chao Qin, Changjun Yin, Zhengdong Zhang
Journal: Cancer Research (2012)

miRNAs play important roles in numerous cellular processes, including development, proliferation, apoptosis, and carcinogenesis. Because altered expression and function of miRNAs has been observed in bladder cancer, we investigated whether genetic variations in miRNAs are associated with bladder cancer risk and prognosis. Using bioinformatics tools, we selected five single-nucleotide polymorphisms located in miRNAs and used these to evaluate miRNA-disease associations in a two-stage model, consisting of 1,019 bladder cancer cases and 1,182 controls (683 cases and 728 controls in the training set and 336 cases and 454 controls in the test set). We found that miR-146a rs2910164 C allele was associated with significantly decreased risk of bladder cancer in both the training and test sets, as well as the combined set [OR = 0.80, 95% confidence interval (CI) = 0.71-0.90, P = 2.92 × 10(-4)]. Furthermore, the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence, compared with the GG genotype (P = 0.016). Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated expression of IRAK1 and TRAF6 in bladder cancer cells. Additional examination of 64 bladder cancer tissues showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele (P = 0.010). Taken together, our findings show that miR-146a rs2910164 plays an important role in the risk and recurrence of bladder cancer, suggesting it may represent a biomarker for risk prevention and therapeutic intervention. Further larger and prospective cohorts are needed to validate our findings.
Phylogenetic profiling of the Arabidopsis thalianaproteome: what proteins distinguish plants from other organisms?
Authors: Rodrigo A Gutiérrez, Pamela J Green, Kenneth Keegstra, John B Ohlrogge
Journal: Genome biology (2004)

The availability of the complete genome sequence of Arabidopsis thaliana together with those of other organisms provides an opportunity to decipher the genetic factors that define plant form and function. To begin this task, we have classified the nuclear protein-coding genes of Arabidopsis thaliana on the basis of their pattern of sequence similarity to organisms across the three domains of life.We identified 3,848 Arabidopsis proteins that are likely to be found solely within the plant lineage. More than half of these plant-specific proteins are of unknown function, emphasizing the general lack of knowledge of processes unique to plants. Plant-specific proteins that are membrane-associated and/or targeted to the mitochondria or chloroplasts are the most poorly characterized. Analyses of microarray data indicate that genes coding for plant-specific proteins, but not evolutionarily conserved proteins, are more likely to be expressed in an organ-specific manner. A large proportion (13%) of plant-specific proteins are transcription factors, whereas other basic cellular processes are under-represented, suggesting that evolution of plant-specific control of gene expression contributed to making plants different from other eukaryotes.We identified and characterized the Arabidopsis proteins that are most likely to be plant-specific. Our results provide a genome-wide assessment that supports the hypothesis that evolution of higher plant complexity and diversity is related to the evolution of regulatory mechanisms. Because proteins that are unique to the green plant lineage will not be studied in other model systems, they should be attractive priorities for future studies.