tbuckley/cabot-search huggingface dataset:
CPAP for the Metabolic Syndrome in Patients with Obstructive Sleep Apnea
Authors: Surendra K. Sharma, Swastik Agrawal, Deepak Damodaran, Vishnubhatla Sreenivas, Tamilarasu Kadhiravan, Ramakrishnan Lakshmy, Priya Jagia, Atin Kumar
Journal: New England Journal of Medicine (2011)

Obstructive sleep apnea is associated with an increased prevalence of the metabolic syndrome and its components. It is unclear whether treatment of obstructive sleep apnea syndrome with continuous positive airway pressure (CPAP) would modify these outcomes.In our double-blind, placebo-controlled trial, we randomly assigned patients with obstructive sleep apnea syndrome to undergo 3 months of therapeutic CPAP followed by 3 months of sham CPAP, or vice versa, with a washout period of 1 month in between. Before and after each intervention, we obtained measurements of anthropometric variables, blood pressure, fasting blood glucose levels, insulin resistance (with the use of homeostasis model assessment), fasting blood lipid profile, glycated hemoglobin levels, carotid intima-media thickness, and visceral fat. The metabolic syndrome was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria, with Asian cutoff values for abdominal obesity.A total of 86 patients completed the study, 75 (87%) of whom had the metabolic syndrome. CPAP treatment (vs. sham CPAP) was associated with significant mean decreases in systolic blood pressure (3.9 mm Hg; 95% confidence interval [CI], 1.4 to 6.4; P=0.001), diastolic blood pressure (2.5 mm Hg; 95% CI, 0.9 to 4.1; P<0.001), serum total cholesterol (13.3 mg per deciliter; 95% CI, 5.3 to 21.3; P=0.005), non-high-density lipoprotein cholesterol (13.3 mg per deciliter; 95% CI, 4.8 to 21.8; P=0.009), low-density lipoprotein cholesterol (9.6 mg per deciliter; 95% CI, 2.5 to 16.7; P=0.008), triglycerides (18.7 mg per deciliter; 95% CI, 4.3 to 41.6; P=0.02), and glycated hemoglobin (0.2%; 95% CI, 0.1 to 0.4; P=0.003). The frequency of the metabolic syndrome was reduced after CPAP therapy (reversal found in 11 of 86 patients [13%] undergoing CPAP therapy vs. 1 of 86 [1%] undergoing sham CPAP). Accelerated hypertension developed 1 patient receiving CPAP therapy first, intolerance to CPAP developed in 2 others, and another patient declined to continue sham CPAP.In patients with moderate-to-severe obstructive sleep apnea syndrome, 3 months of CPAP therapy lowers blood pressure and partially reverses metabolic abnormalities. (Funded by Pfizer; ClinicalTrials.gov number, NCT00694616.).
Topoisomerase II Alpha and Responsiveness of Breast Cancer to Adjuvant Chemotherapy
Authors: F. P. O'Malley, S. Chia, D. Tu, L. E. Shepherd, M. N. Levine, V. H. Bramwell, I. L. Andrulis, K. I. Pritchard
Journal: JNCI Journal of the National Cancer Institute (2009)

Amplification or deletion of the topoisomerase II alpha ( TOP2A ) gene in breast cancers has been postulated to be more closely associated with responsiveness to anthracycline-containing chemotherapy than amplification of the human epidermal growth factor receptor type 2 ( HER2 ) gene. We studied 438 tumors from 710 premenopausal women with node-positive breast cancer who received cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) as adjuvant chemotherapy in the randomized National Cancer Institute of Canada Clinical Trials Group Mammary 5 (MA.5) trial. TOP2A alterations and HER2 amplification were quantified by fluorescence in situ hybridization. The association of TOP2A and HER2 status with recurrence-free survival (RFS) and overall survival (OS) in the two treatment groups was analyzed using Kaplan–Meier curves, the log-rank test, and Cox proportional hazard models. All statistical tests were two-sided. In patients whose tumors showed TOP2A alterations (either amplifications or deletions), treatment with CEF was statistically significantly superior to treatment with CMF in terms of RFS (adjusted hazard ratio [HR] = 0.35, 95% confidence interval [CI] = 0.17 to 0.73, P = .005) and OS (adjusted HR = 0.33, 95% CI = 0.15 to 0.75, P = .008). In patients without TOP2A amplification or deletion, the corresponding adjusted hazard ratios for RFS and OS were 0.90 (95% CI = 0.66 to 1.23, P = .49) and 1.09 (95% CI = 0.77 to 1.56, P = .62). Adjusted tests of interaction between treatment and TOP2A status were P = .09 for RFS and P = .02 for OS. Adjusted tests of interaction between treatment and HER2 status were P = .008 for RFS and P = .02 for OS. TOP2A gene alterations (amplifications or deletions) are associated with an increase in responsiveness to anthracycline-containing chemotherapy regimens relative to non-anthracycline regimens that is similar to that seen in patients with HER2 amplification.
THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES
Authors: Peyton Rous
Journal: The Journal of Experimental Medicine (1925)

In continuation of the observations on vital staining by means of phthalein indicators, reported in a previous paper, some members of the group with acid ranges have been employed. The results accord closely with those already obtained, in pointing to the existence of characteristic differences in the reaction within the organs. Roughly speaking, these latter fall into two groups. Within the members of the one a noteworthy acidity would appear to prevail, whereas in those of the other acidity seems slight at most, and in a few instances signs of a faint alkalinity are to be met. In general the "acid" organs are such as have a great metabolic activity whereas the "neutral" group manifest but an inconsiderable one. All of the tissues examined seem to be relatively acid compared with the blood plasma. The findings with the phthaleins as a group are discussed.
Association between focal erosions and generalised bone loss in psoriatic arthritis
Authors: A. P. Anandarajah, M. El-Taha, C. Peng, G. Reed, J. D. Greenberg, C. T. Ritchlin
Journal: Annals of the Rheumatic Diseases (2011)

Bone erosions are frequent in patients with psoriatic arthritis (PsA) but the prevalence of generalised bone loss in PsA is not well understood.1,–,6 To formally address this question, we analysed data from the Consortium of Rheumatology Researchers of North America registry.

Erosions on plain x-rays of hands and feet and T-scores at the lumbar spine, femoral neck and total hip were identified as the key outcome variables. Key independent variables included gender, age, weight, C reactive protein, functional status, Health Assessment Questionnaire, body mass index and medication use. Medications included methotrexate, other disease-modifying antirheumatic drugs (DMARDs), anti-tumour necrosis factor (anti-TNF) agents, prednisone use (yes or no) and prednisone dose …
Oxidative stress in serum of patients with alpha-1 antitrypsin deficiency
Authors: Francisco Dasí, Mónica Amor, Francisco Sanz, Pilar Codoñer-Franch, María Mercedes Navarro-García, Amparo Escribano
Journal: European Respiratory Journal (2013)

Background : Oxidative stress (OE) has been shown to be a contributing factor in the development of liver and lung damage in animal models of alpha-1 antitrypsin deficiency (AATD).   Rationale and aims : In humans, AAT shows a high degree of variability and it has been proposed that emphysema progression is heavily influenced by the antioxidant defenses of the lung. We hypothesize that those patients with low AAT levels and high OE levels will be more prone to develop severe emphysema. The aim of this study is to determine in serum the OE profile of children with AATD and study the association with the AAT phenotype.   Methods : Forty-seven children diagnosed with AATD were prospectively included in the study. Patients were classified in three risk groups of developing lung disease: low (MM, MS; SS), intermediate (MZ; SZ) and high risk (ZZ). The OE status was evaluated in serum by monitoring the total glutathione, oxidized vs reduced glutathione ratio (GSSG/GSH) and the oxidation products 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA) and protein carbonyl (PC).   Results : High-risk (ZZ) patients showed significantly higher GSSG/GSH ratio, 8-OHdG, MDA and PC but lower levels of total glutathione than the low-risk group. Interestingly, intermediate-risk (MZ and SZ patients) patients showed OE values between high and low risk patients.   Conclusions : OE is increased in serum of high-risk (ZZ) AATD patients, indicating that OE could be an important contributing factor in the development of lung disease when AAT levels are low. Our results open up a new strategy to use OE parameters as biomarkers of lung disease progression.   Funding Sources : Supported by SVN, GVA AP-096/11, ISCIII PI11/02884 grants.
Epithelial Line From Normal Human Colon Mucosa&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: B S Danes, E Sutanto
Journal: JNCI Journal of the National Cancer Institute (1982)

An epithelial line was established from an explant culture derived from human colon mucosa exhibiting a normal phenotype by taking advantage of two differences in in vitro cell behavior of mixed cell (epithelial-fibroblast) monolayer [rate of adherence to a plastic surface from a suspension and toxicity to collagenase (25 U/ml medium) in the culture medium]. Cells with an epithelial morphology could be identified at all times throughout the first 5 culture months--first as epithelial sheets migrating from explants, then as small clusters within the fibroblast monolayer, and finally after 5 months of selective culturing as the only cell type present. The line maintained an epithelium-like morphology and growth pattern through 27 continuous culture months (35 subcultures) and was clearly distinguishable from colon fibroblast cultures grown under the same conditions. The ultrastructural features of this line that grew as a continuum included extensive membrane interdigitations with intercellular junctions, tonofilaments, mucus droplets, no Weibel-Palade bodies (characteristic of endothelial cells), and microridges uniformly covering the cell surfaces; all of these features were absent in colon fibroblast cultures. Growth kinetics (generation time, saturation density, and life-span) were distinctly different from those of colon fibroblast cultures grown under the same conditions. During 27 continuous culture months, the cells remained diploid (2-3% hyperdiploidy) and showed no evidence of senescence.
Altered Lipid Metabolism in Human Platelets after Primary Aggregation
Authors: Daniel Deykin
Journal: Journal of Clinical Investigation (1973)

Thrombin and poly-l-lysine alter the incorporation of acetate, glycerol, and fatty acids into the lipids of washed human platelets. Both aggregating agents decrease the incorporation of acetate into all lipid classes other than free fatty acids. Similarly, glycerol incorporation into complex lipids is impaired by both thrombin and polylysine. Thrombin caused marked depression of the incorporation of palmitic acid into both lecithin and triglycerides. By contrast it enhanced the incorporation of oleic acid into lecithin, but not into triglycerides. The data suggest that the process of primary platelet aggregation is associated with a defect in the assembly of complex lipids.
Retrospective comparison of bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for allogeneic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes
Authors: Philippe Guardiola, Volker Runde, Andrea Bacigalupo, Tapani Ruutu, Franco Locatelli, Marc A. Boogaerts, Antonio Pagliuca, Jan J. Cornelissen, Harry C. Schouten, Enric Carreras, Jürgen Finke, Anja van Biezen, Ronald Brand, Dietger Niederwieser, Eliane Gluckman, Theo M. de Witte
Journal: Blood (2002)
Traumatic rupture of the thoracic aorta
Authors: G. Keen, R. A. Bradbrook, F. McGinn
Journal: Thorax (1969)

Seven patients who had traumatic ruptures of the thoracic aorta are reported. Four of these died within a few hours of admission, allowing no opportunity for diagnosis or treatment. However, three survived long enough for elective surgery to be undertaken. A diagnosis of ruptured aorta was missed in one patient (case 2), and the difficulties of diagnosing this condition, even during thoracotomy, are emphasized. The value of serial chest radiography and forward aortography is discussed. Two of these patients underwent successful aortic repair, using left atrio-femoral bypass.
Postradiotherapy Neck Dissection for Lymph Node–Positive Head and Neck Cancer: The Use of Computed Tomography to Manage the Neck
Authors: Stanley L. Liauw, Anthony A. Mancuso, Robert J. Amdur, Christopher G. Morris, Douglas B. Villaret, John W. Werning, William M. Mendenhall
Journal: Journal of Clinical Oncology (2006)

Purpose To determine how to use node response on computed tomography (CT) to indicate the need for neck dissection. Patients and Methods Five hundred fifty patients with lymph node–positive head and neck cancer were treated between 1990 and 2002 with radiotherapy (RT) at a median dose of 74.4 Gy; 24% of these patients (n = 133) were treated with chemotherapy. Three hundred forty-one patients (62%) underwent planned post-RT neck dissection. Physical examination and contrast-enhanced CT were performed 30 days after completion of RT. CT images were reviewed in 211 patients for lymph node size (largest axial dimension) and presence of a focal abnormality (lucency, enhancement, or calcification). By correlating post-RT CT to neck dissection pathology, criteria associated with a low likelihood of residual disease were identified. A subset of patients who fit these criteria of radiographic response who did not undergo post-RT neck dissection was observed for recurrence. Results Radiographic complete response (rCR) was defined as the absence of any large (&gt; 1.5 cm) or focally abnormal lymph node. Correlation of response with neck dissection pathology indicated a negative predictive value of 77% for complete clinical response and 94% for rCR. In 32 patients (median follow-up time, 3.2 years) with rCR who did not undergo post-RT neck dissection, the 5-year ultimate neck control rate (100%) and cause-specific survival rate (72%) were not significantly different from the rates of patients with a negative post-RT neck dissection. Conclusion Patients with rCR 4 weeks after RT can be spared from a post-RT neck dissection regardless of initial node stage.
The vascular micromilieu in obstructive sleep apnoea
Authors: R. Schulz
Journal: European Respiratory Journal (2005)

Obstructive sleep apnoea (OSA) is increasingly recognised as an important cardiovascular risk factor. In particular, OSA has been shown to increase the risk of diurnal arterial hypertension in a dose-dependent manner, and is now considered as one of the most common causes of secondary arterial hypertension 1, 2. Furthermore, OSA increases the likelihood of developing vaso-occlusive disease, notably myocardial infarction and stroke, although this association seems to be weaker than that observed for arterial hypertension 3. Of note, the epidemiological studies demonstrating a genuine relationship between OSA and cardiovascular disorders have been controlled with respect to confounding factors such as age, body weight and metabolic disease.

How does one explain the causal link between OSA and cardiovascular disease? The repetitive collapse of the upper airway during sleep generates a unique pattern of hypoxia, with frequent cycles of hypoxia and re-oxygenation during the night, and a constant normoxia while awake. Accumulating evidence suggests that this chronic intermittent hypoxia causes a specific disturbance in the vascular micromilieu, with vasoconstrictive, pro-inflammatory and pro-coagulant forces predominating. Finally, the disturbance in the vascular micromilieu leads to endothelial dysfunction in these patients 4. This reduction in endothelial-dependent vasorelaxation has been established as a pathogenic factor in both systemic arterial hypertension and atherosclerosis. Treatment of OSA by continuous positive airway pressure (CPAP) ventilation not only eliminates apnoeas and nocturnal oxygen desaturations, but also exerts cardio-protective effects. …
Trends in Postpartum Diabetes Screening and Subsequent Diabetes and Impaired Fasting Glucose Among Women With Histories of Gestational Diabetes Mellitus
Authors: Assiamira Ferrara, Tiffany Peng, Catherine Kim
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to examine trends in postpartum glucose screening for women with gestational diabetes mellitus (GDM), predictors of screening, trends in postpartum impaired fasting glucose (IFG) and diabetes, and diabetes and pre-diabetes detected by postpartum fasting plasma glucose (FPG) versus a 75-g oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS—This was a cohort study of 14,448 GDM pregnancies delivered between 1995 and 2006. Postpartum screening was defined as performance of either an FPG or OGTT at least 6 weeks after delivery and within 1 year of delivery. RESULTS—Between 1995 and 2006, the age- and race/ethnicity-adjusted proportion of women who were screened postpartum rose from 20.7% (95% CI 17.8–23.5) to 53.8% (51.3–56.3). Older age, Asian or Hispanic race/ethnicity, higher education, earlier GDM diagnosis, use of diabetes medications during pregnancy, and more provider contacts after delivery were independent predictors of postpartum screening. Obesity and higher parity were independently associated with lower screening performance. Among women who had postpartum screening, the age- and race/ethnicity-adjusted proportion of IFG did not change over time (24.2 [95% CI 20.0–27.8] in 1995–1997 to 24.3 [22.6–26.0] in 2004–2006), but the proportion of women with diabetes decreased from 6.1 (95% CI 4.2–8.1) in 1995–1997 to 3.3 (2.6–4.0) in 2004–2006. Among women who received an OGTT in 2006, 38% of the 204 women with either diabetes or pre-diabetes were identified only by the 2-h glucose measurements. CONCLUSIONS—Postpartum screening has increased over the last decade, but it is still suboptimal. Compared with FPGs alone, the 2-h values identify a higher proportion of women with diabetes or pre-diabetes amenable to intervention.
Human Adrenomedullin Up-regulates Interleukin-13 Receptor α2 Chain in Prostate Cancer<i>In vitro</i>and<i>In vivo</i>: A Novel Approach to Sensitize Prostate Cancer to Anticancer Therapy
Authors: Bharat H. Joshi, Pamela Leland, Alfonso Calvo, Jeffrey E. Green, Raj K. Puri
Journal: Cancer Research (2008)

Abstract Interleukin-13 (IL-13) receptor α2 (IL-13Rα2), a high-affinity IL-13 binding subunit and a tumor antigen, is amplified in a variety of human tumor cell lines and tumors in vivo. By cDNA microarray, we have shown that gene transfer of human and rat adrenomedullin (AM) up-regulates IL-13Rα2 in a human prostate tumor cell line. Here, we show that IL-13Rα2 mRNA and protein are also up-regulated in PC-3 prostate tumor cells by recombinant AM (rAM) and human synthetic AM peptide in a dose-dependent manner in vitro and in vivo in mouse prostate tumor model. The 8- to 10-fold up-regulation of IL-13Rα2 by rAM or AM peptide in prostate tumor cells in vitro and in vivo increased their sensitivity to IL-13PE cytotoxin consisting of IL-13 and a truncated form of Pseudomonas exotoxin. Immunodeficient mice with established prostate tumors transfected with AM or treated with AM peptide showed reduction in tumor size by intratumoral administration of IL-13PE in a dose-dependent manner. At the highest dose (three 100 μg/kg/d every alternate day), &amp;gt;70% reduction of tumor size was observed compared with controls (P ≤ 0.01). These results indicate that two completely unrelated hormones (AM and IL-13) are closely related to each other and that we have identified a novel role of AM in sensitizing certain types of prostate tumors to IL-13R–directed therapeutic agent. [Cancer Res 2008;68(22):9311–7]
Gemcitabine concurrent with continuous infusional 5-fluorouracil in advanced biliary cancers: a review of the Princess Margaret Hospital experience
Authors: J.J. Knox, D. Hedley, A. Oza, L.L. Siu, G.R. Pond, M.J. Moore
Journal: Annals of Oncology (2004)

Unresectable biliary tract cancer has a very poor prognosis. A combination of weekly gemcitabine plus continuous infusional 5-fluorouracil (5-FU) (GEM/CVI 5-FU) was evaluated as therapy for this cancer.The charts of 27 patients with advanced biliary tract adenocarcinoma treated with GEM/CVI 5-FU at the Princess Margaret Hospital were evaluated for response, survival and toxicity. The treatment consisted of a 30-min infusion of gemcitabine at 900 mg/m(2) on days 1, 8 and 15 of a 28-day cycle plus 5-FU given via a peripherally inserted central line at 200 mg/m(2)/day continuously for 21 days, every 28 days.Objective responses were observed in nine patients (33%; 95% confidence interval 17% to 54%). An additional eight patients (30%) achieved stable disease for a median of 4 months (range 2.3-11). Median time to progression and overall survival were 3.7 and 5.3 months, respectively. Direct chemotherapy-related toxicity was mild, with only 11% grade > or =3 myelosuppression. Central venous catheter complications were common (26%). There were no treatment-related deaths.This study shows that GEM/CVI 5-FU is active and well tolerated in advanced and metastatic biliary tract cancers.
Targets of the Tumor Suppressor <i>miR-200</i> in Regulation of the Epithelial–Mesenchymal Transition in Cancer
Authors: Mark J. Schliekelman, Don L. Gibbons, Vitor M. Faca, Chad J. Creighton, Zain H. Rizvi, Qing Zhang, Chee-Hong Wong, Hong Wang, Christin Ungewiss, Young-Ho Ahn, Dong-Hoon Shin, Jonathan M. Kurie, Samir M. Hanash
Journal: Cancer Research (2011)

The microRNA-200 (miR-200) family restricts epithelial-mesenchymal transition (EMT) and metastasis in tumor cell lines derived from mice that develop metastatic lung adenocarcinoma. To determine the mechanisms responsible for EMT and metastasis regulated by this microRNA, we conducted a global liquid chromatography/tandem mass spectrometry analysis to compare metastatic and nonmetastatic murine lung adenocarcinoma cells which had undergone EMT because of loss of miR-200. An analysis of syngeneic tumors generated by these cells identified multiple novel proteins linked to metastasis. In particular, the analysis of conditioned media, cell surface proteins, and whole-cell lysates from metastatic and nonmetastatic cells revealed large-scale modifications in the tumor microenvironment. Specific increases were documented in extracellular matrix (ECM) proteins, peptidases, and changes in distribution of cell adhesion proteins in the metastatic cell lines. Integrating proteomic data from three subproteomes, we defined constituents of a multilayer protein network that both regulated and mediated the effects of TGFβ. Lastly, we identified ECM proteins and peptidases that were directly regulated by miR-200. Taken together, our results reveal how expression of miR-200 alters the tumor microenvironment to inhibit the processes of EMT and metastasis.
Learning to internalize: A developmental perspective
Authors: Bruce Hood
Journal: Behavioral and Brain Sciences (2001)

As Hecht points out, finding unequivocal evidence for phylogenetic knowledge structures is problematic, if not impossible. But if phylogeny could be dropped, then internalization starts to resemble the “theory theory” approaches of developmental psychology. For example, an appreciation of falling objects leads to a very strong bias that could be regarded as internalized knowledge acquired during ontogeny. [Hecht; Shepard]
Cold temperature induces mucin hypersecretion from normal human bronchial epithelial cells in vitro through a transient receptor potential melastatin 8 (TRPM8)–mediated mechanism
Authors: MinChao Li, Qi Li, Gang Yang, Victor P. Kolosov, Juliy M. Perelman, Xiang Dong Zhou
Journal: Journal of Allergy and Clinical Immunology (2011)