tbuckley/cabot-search huggingface dataset:
Risk of angioedema following invasive or surgical procedures in <scp>HAE</scp> type I and <scp>II</scp> – the natural history
Authors: E. Aygören‐Pürsün, I. Martinez Saguer, W. Kreuz, T. Klingebiel, D. Schwabe
Journal: Allergy (2013)

Background Hereditary angioedema (HAE), caused by deficiency in C1-inhibitor (C1-INH), leads to unpredictable edema of subcutaneous tissues with potentially fatal complications. As surgery can be a trigger for edema episodes, current guidelines recommend preoperative prophylaxis with C1-INH or attenuated androgens in patients with HAE undergoing surgery. However, the risk of an HAE attack in patients without prophylaxis has not been quantified. Objectives This analysis examined rates of perioperative edema in patients with HAE not receiving prophylaxis. Methods This was a retrospective analysis of records of randomly selected patients with HAE type I or II treated at the Frankfurt Comprehensive Care Centre. These were examined for information about surgical procedures and the presence of perioperative angioedema. Results A total of 331 patients were included; 247 underwent 700 invasive procedures. Of these procedures, 335 were conducted in 144 patients who had not received prophylaxis at the time of surgery. Categories representing significant numbers of procedures were abdominal (n = 113), ENT (n = 71), and gynecological (n = 58) procedures. The rate of documented angioedema without prophylaxis across all procedures was 5.7%; in 24.8% of procedures, the presence of perioperative angioedema could not be excluded, leading to a maximum potential risk of 30.5%. Predictors of perioperative angioedema could not be identified. Conclusion The risk of perioperative angioedema in patients with HAE type I or II without prophylaxis undergoing surgical procedures ranged from 5.7% to 30.5% (CI 3.5–35.7%). The unpredictability of HAE episodes supports current international treatment recommendations to consider short-term prophylaxis for all HAE patients undergoing surgery.
Role of Three-Dimensional Echocardiography in Breast Cancer: Comparison With Two-Dimensional Echocardiography, Multiple-Gated Acquisition Scans, and Cardiac Magnetic Resonance Imaging
Authors: Jonathan Walker, Navdeep Bhullar, Nazanin Fallah-Rad, Matthew Lytwyn, Mehrdad Golian, Tielan Fang, Arthur R. Summers, Pawan K. Singal, Ivan Barac, Iain D. Kirkpatrick, Davinder S. Jassal
Journal: Journal of Clinical Oncology (2010)

In patients with breast cancer, the administration of doxorubicin and trastuzumab is associated with an increased risk of cardiotoxicity. Although multiple-gated acquisition (MUGA) scans and two-dimensional transthoracic echocardiography (TTE) are conventional methods for baseline and serial assessment of left ventricular ejection fraction (LVEF) in these patients, little is known about the use of real-time three-dimensional TTE (RT3D TTE) in this clinical setting. The aim of this study was to assess the accuracy of MUGA, 2D TTE, and RT3D TTE for determining LVEF in comparison to cardiac magnetic resonance imaging (CMR).Between 2007 and 2009 inclusive, 50 female patients with human epidermal growth factor receptor 2-positive breast cancer received adjuvant trastuzumab after doxorubicin. Serial MUGA, 2D TTE, RT3D TTE, and CMR were performed at baseline, 6, and 12 months after the initiation of trastuzumab.A comparison of left ventricular end diastolic volume (LVEDV) demonstrated a modest correlation between 2D TTE and CMR (r = 0.64 at baseline; r = 0.69 at 12 months, respectively). A comparison of LVEDV between RT3D TTE and CMR demonstrated a stronger correlation (r = 0.87 at baseline; r = 0.95 at 12 months, respectively). Although 2D TTE demonstrated a weak correlation with CMR for LVEF assessment (r = 0.31 at baseline, r = 0.42 at 12 months, respectively), both RT3D TTE and MUGA showed a strong correlation when compared with CMR (r = 0.91 at baseline; r = 0.90 at 12 months, respectively).As compared with conventional MUGA, RT3D TTE is a feasible, accurate, and reproducible alternate imaging modality for the serial monitoring of LVEF in patients with breast cancer.
The XX sex chromosome complement in mice is associated with increased spontaneous lupus compared with XY
Authors: Manda V Sasidhar, Noriko Itoh, Stefan M Gold, Gregory W Lawson, Rhonda R Voskuhl
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Many autoimmune diseases are characterised by a female predominance. This may be caused by sex hormones, sex chromosomes or both. This report uses a transgenic mouse model to investigate how sex chromosome complement, not confounded by differences in gonadal type, might contribute to lupus pathogenesis. <h3>Methods</h3> Transgenic NZM2328 mice were created by deletion of the Sry gene from the Y chromosome, thereby separating genetic from gonadal sex. Survival, renal histopathology and markers of immune activation were compared in mice carrying the XX versus the XY<sup>−</sup> sex chromosome complement, with each genotype being ovary bearing. <h3>Results</h3> Mice with XX sex chromosome complement compared with XY<sup>−</sup> exhibited poorer survival rates and increased kidney pathology. Splenic T lymphocytes from XX mice demonstrated upregulated X-linked CD40 ligand expression and higher levels of activation markers ex vivo. Increased MMP, TGF and IL-13 production was found, while IL-2 was lower in XX mice. An accumulation of splenic follicular B cells and peritoneal marginal zone B cells was observed, coupled with upregulated costimulatory marker expression on B cells in XX mice. <h3>Conclusion</h3> These data show that the XX sex chromosome complement, compared with XY<sup>−</sup>, is associated with accelerated spontaneous lupus.
Sexuality in Patients with Noninvasive Mechanical Ventilation Due to Chronic Respiratory Failure
Authors: BERND SCHÖNHOFER, KIRSTEN VON SYDOW, THOMAS BUCHER, MARCO NIETSCH, STEFAN SUCHI, DIETER KÖHLER, PAUL W. JONES
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

In patients with chronic respiratory failure (CRF) noninvasive mechanical ventilation (NMV) improves quality of life. We studied some basic issues concerning sexuality in patients with NMV. In 383 patients with NMV for CRF (age, > 40 yr) physiologic data (lung function, blood gases, and exercise) were taken from within the 6 mo period before enrollment. The questionnaire was focused on sexuality after initiation of NMV. Of the patients, 54.3% sent back the questionnaire. NMV was used for 41.1 +/- 27.0 mo. A total of 34.1% of patients were sexually active. Compared with patients receiving NMV, control persons had a higher rate of sexual activity (84%, p < 0.0001) and masturbation rate (13 versus 40%). Sexually active patients had greater VC (2.1 versus 1.8 L), higher FEV(1) (1.4 versus 1.1 L), higher Pa(O(2)) at rest (64.0 versus 60.4 mm Hg), a higher maximal work load (72.0 versus 58.8 W), were younger, and most of them were married or had sexual partners. Changes in sexual activity after NMV initiation were reported to be as follows: "Nothing changed," 46.3%; "less active," 35.8%; "more active," 12.6%; and "fantasy increased," 10.5%. Increased sexual fantasy predominated in men. "Sexually active" patients with NMV had sexual intercourse 5.4 +/- 4.8 times per month. Sexuality in patients receiving NMV for CRF is markedly reduced compared with normal subjects. In half of the patients, sexual activity is influenced by initiation of NMV.
Prevalence and Clinical Outcome of Hyperglycemia in the Perioperative Period in Noncardiac Surgery
Authors: Anna Frisch, Prakash Chandra, Dawn Smiley, Limin Peng, Monica Rizzo, Chelsea Gatcliffe, Megan Hudson, Jose Mendoza, Rachel Johnson, Erica Lin, Guillermo E. Umpierrez
Journal: Diabetes Care (2010)

OBJECTIVE Hospital hyperglycemia, in individuals with and without diabetes, has been identified as a marker of poor clinical outcome in cardiac surgery patients. However, the impact of perioperative hyperglycemia on clinical outcome in general and noncardiac surgery patients is not known. RESEARCH DESIGN AND METHODS This was an observational study with the aim of determining the relationship between pre- and postsurgery blood glucose levels and hospital length of stay (LOS), complications, and mortality in 3,184 noncardiac surgery patients consecutively admitted to Emory University Hospital (Atlanta, GA) between 1 January 2007 and 30 June 2007. RESULTS The overall 30-day mortality was 2.3%, with nonsurvivors having significantly higher blood glucose levels before and after surgery (both P &amp;lt; 0.01) than survivors. Perioperative hyperglycemia was associated with increased hospital and intensive care unit LOS (P &amp;lt; 0.001) as well as higher numbers of postoperative cases of pneumonia (P &amp;lt; 0.001), systemic blood infection (P &amp;lt; 0.001), urinary tract infection (P &amp;lt; 0.001), acute renal failure (P = 0.005), and acute myocardial infarction (P = 0.005). In multivariate analysis (adjusted for age, sex, race, and surgery severity), the risk of death increased in proportion to perioperative glucose levels; however, this association was significant only for patients without a history of diabetes (P = 0.008) compared with patients with known diabetes (P = 0.748). CONCLUSIONS Perioperative hyperglycemia is associated with increased LOS, hospital complications, and mortality after noncardiac general surgery. Randomized controlled trials are needed to determine whether perioperative diabetes management improves clinical outcome in noncardiac surgery patients.
Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells
Authors: Ratana Banjerdpongchai, Prachya Kongtawelert, Orawan Khantamat, Chantragan Srisomsap, Daranee Chokchaichamnankit, Pantipa Subhasitanont, Jisnuson Svasti
Journal: Journal of Hematology & Oncology (2010)

Zearalenone (ZEA) is a phytoestrogen from Fusarium species. The aims of the study was to identify mode of human leukemic cell death induced by ZEA and the mechanisms involved. Cell cytotoxicity of ZEA on human leukemic HL-60, U937 and peripheral blood mononuclear cells (PBMCs) was performed by using 3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Reactive oxygen species production, cell cycle analysis and mitochondrial transmembrane potential reduction was determined by employing 2',7'-dichlorofluorescein diacetate, propidium iodide and 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, respectively. Caspase-3 and -8 activities were detected by using fluorogenic Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC) and Ile-Glu-Thr-Asp-7-amino-4-methylcoumarin (IETD-AMC) substrates, respectively. Protein expression of cytochrome c, Bax, Bcl-2 and Bcl-xL was performed by Western blot. The expression of proteins was assessed by two-dimensional polyacrylamide gel-electrophoresis (PAGE) coupled with LC-MS2 analysis and real-time reverse transcription polymerase chain reaction (RT-PCR) approach. ZEA was cytotoxic to U937 > HL-60 > PBMCs and caused subdiploid peaks and G1 arrest in both cell lines. Apoptosis of human leukemic HL-60 and U937 cell apoptosis induced by ZEA was via an activation of mitochondrial release of cytochrome c through mitochondrial transmembrane potential reduction, activation of caspase-3 and -8, production of reactive oxygen species and induction of endoplasmic reticulum stress. Bax was up regulated in a time-dependent manner and there was down regulation of Bcl-xL expression. Two-dimensional PAGE coupled with LC-MS2 analysis showed that ZEA treatment of HL-60 cells produced differences in the levels of 22 membrane proteins such as apoptosis inducing factor and the ER stress proteins including endoplasmic reticulum protein 29 (ERp29), 78 kDa glucose-regulated protein, heat shock protein 90 and calreticulin, whereas only ERp29 mRNA transcript increased. ZEA induced human leukemic cell apoptosis via endoplasmic stress and mitochondrial pathway.
Nox1 Is Involved in Angiotensin II–Mediated Hypertension
Authors: Kuniharu Matsuno, Hiroyuki Yamada, Kazumi Iwata, Denan Jin, Masato Katsuyama, Masato Matsuki, Shinji Takai, Kiyofumi Yamanishi, Mizuo Miyazaki, Hiroaki Matsubara, Chihiro Yabe-Nishimura
Journal: Circulation (2005)

Increased production of reactive oxygen species (ROSs) by angiotensin II (Ang II) is involved in the initiation and progression of cardiovascular diseases. NADPH oxidase is a major source of superoxide generated in vascular tissues. Although Nox1 has been identified in vascular smooth muscle cells as a new homolog of gp91phox (Nox2), a catalytic subunit of NADPH oxidase, the pathophysiological function of Nox1-derived ROSs has not been fully elucidated. To clarify the role of Nox1 in Ang II-mediated hypertension, we generated Nox1-deficient (-/Y) mice.No difference in the baseline blood pressure was observed between Nox1(+/Y) and Nox1(-/Y). Infusion of Ang II induced a significant increase in mean blood pressure, accompanied by augmented expression of Nox1 mRNA and superoxide production in the aorta of Nox1(+/Y), whereas the elevation in blood pressure and production of superoxide were significantly blunted in Nox1(-/Y). Conversely, the infusion of pressor as well as subpressor doses of Ang II did elicit marked hypertrophy in the thoracic aorta of Nox1(-/Y) similar to Nox1(+/Y). Administration of a nitric oxide synthase inhibitor (L-NAME) to Nox1(+/Y) did not affect the Ang II-mediated increase in blood pressure, but it abolished the suppressed pressor response to Ang II in Nox1(-/Y). Finally, endothelium-dependent relaxation and the level of cGMP in the isolated aorta were preserved in Nox1(-/Y) infused with Ang II.A pivotal role for ROSs derived from Nox1/NADPH oxidase was suggested in the pressor response to Ang II by reducing the bioavailability of nitric oxide.
Long-term outcomes of patients with extensively drug-resistant tuberculosis in South Africa: a cohort study
Authors: Elize Pietersen, Elisa Ignatius, Elizabeth M Streicher, Barbara Mastrapa, Xavier Padanilam, Anil Pooran, Motasim Badri, Maia Lesosky, Paul van Helden, Frederick A Sirgel, Robin Warren, Keertan Dheda
Journal: The Lancet (2014)
Recombinant human interleukin 5 is a selective activator of human eosinophil function.
Authors: A F Lopez, C J Sanderson, J R Gamble, H D Campbell, I G Young, M A Vadas
Journal: The Journal of Experimental Medicine (1988)

Human rIL-5 was found to selectively stimulate morphological changes and the function of human eosinophils. This molecule is thus a prime candidate for the selective eosinophilia and eosinophil activation seen in disease.
The Complete Maternal and Paternal Mitochondrial Genomes of the Mediterranean Mussel Mytilus galloprovincialis: Implications for the Doubly Uniparental Inheritance Mode of mtDNA
Authors: Athanasia Mizi, Eleftherios Zouros, Nicholas Moschonas, George C. Rodakis
Journal: Molecular Biology and Evolution (2005)

The maternal (F) and paternal (M) mitochondrial genomes of the mussel Mytilus galloprovincialis have diverged by about 20% in nucleotide sequence but retained identical gene content and gene arrangement and similar nucleotide composition and codon usage bias.Both lack the ATPase8 subunit gene, have two tRNAs for methionine and a longer open-reading frame for cox3 than seen in other mollusks.Between the F and M genomes, tRNAs are most conserved followed by rRNAs and protein-coding genes, even though the degree of divergence varies considerably among the latter.Divergence at nad3 is exceptionally low most likely because this gene includes the origin of transcription of the lagging strand (O L ).Noncoding regions are the least conserved with the notable exception of the central domain of the main control region and a segment of another noncoding region immediately following nad3.The amino acid divergence (14%) of the two genomes is smaller than in two other pairs of conspecific genomes that are available in GenBank, that of the clam Venerupis philippinarum (34%) and of the fresh water mussel Inversidens japanensis (50%), suggesting that doubly uniparental inheritance of mtDNA emerged at different times in the three species or that there has been a relatively recent replacement of the male genome by the female in the Mytilus line.The latter hypothesis is supported from phylogenetic and population studies of Mytilidae.That the M genome contains a full complement of genes with no premature termination codons argues against it being a selfish element that rides with the sperm.It is shorter than the F by 118 bp, which apparently cannot account for the postulated replicative advantage of this genome over the F in male gonads.The high similarity of the two genomes explains why the F genome may assume the role of the M genome, but it does not exclude the possibility that for this to happen some M-specific sequences must be transferred on to the F genome by means of recombination.If such sequences exist they would most likely be located in noncoding regions.
Maximum-Likelihood Tree Estimation Using Codon Substitution Models with Multiple Partitions
Authors: Stefan Zoller, Veronika Boskova, Maria Anisimova
Journal: Molecular Biology and Evolution (2015)

Many protein sequences have distinct domains that evolve with different rates, different selective pressures, or may differ in codon bias. Instead of modeling these differences by more and more complex models of molecular evolution, we present a multipartition approach that allows maximum-likelihood phylogeny inference using different codon models at predefined partitions in the data. Partition models can, but do not have to, share free parameters in the estimation process. We test this approach with simulated data as well as in a phylogenetic study of the origin of the leucin-rich repeat regions in the type III effector proteins of the pythopathogenic bacteria Ralstonia solanacearum. Our study does not only show that a simple two-partition model resolves the phylogeny better than a one-partition model but also gives more evidence supporting the hypothesis of lateral gene transfer events between the bacterial pathogens and its eukaryotic hosts.
Obesity Is an Independent Prognostic Variable in Colon Cancer Survivors
Authors: Frank A. Sinicrope, Nathan R. Foster, Daniel J. Sargent, Michael J. O'Connell, Cathryn Rankin
Journal: Clinical Cancer Research (2010)

Obesity is associated with an increased risk of colon cancer. However, the influence of body mass index (BMI) on the prognosis of colon cancer survivors and its relationship to gender remains unknown.BMI (kg/m(2)) was categorized in patients with tumor-node-metastasis stage II and III colon carcinomas (n = 4,381) enrolled in seven randomized trials of 5-fluorouracil-based adjuvant chemotherapy. Cox proportional hazards models were used to determine the association of BMI with disease-free survival (DFS) and overall survival (OS).Among colon cancer patients, 868 (20%) were obese (BMI, >or=30 kg/m(2)), of which 606 were class 1 (BMI, 30-34 kg/m(2)) and 262 were class 2,3 (BMI, >or=35 kg/m(2)). Obese versus normal-weight patients were more likely to be younger, have distal tumors, show intact DNA mismatch repair, and have more lymph node metastases (P < 0.017). In a multivariate analysis, BMI was significantly associated with both DFS (P = 0.030) and OS (P = 0.0017). Men with class 2,3 obesity showed reduced OS compared with normal-weight men [hazard ratio, 1.35; 95% confidence interval, 1.02-1.79; P = 0.039]. Women with class I obesity had reduced OS [hazard ratio, 1.24; 95% confidence interval, 1.01-1.53; P = 0.045] compared with normal-weight women. Overweight status was associated with improved OS in men (P = 0.006), and underweight women had significantly worse OS (P = 0.019). BMI was not predictive of therapeutic benefit.Obesity is an independent prognostic variable in colon cancer survivors and shows gender-related differences. These data suggest that obesity-related biological factors can influence clinical outcome.
RG7116, a Therapeutic Antibody That Binds the Inactive HER3 Receptor and Is Optimized for Immune Effector Activation
Authors: Christian Mirschberger, Christian B. Schiller, Michael Schräml, Nikolaos Dimoudis, Thomas Friess, Christian A. Gerdes, Ulrike Reiff, Valeria Lifke, Gabriele Hoelzlwimmer, Irene Kolm, Karl-Peter Hopfner, Gerhard Niederfellner, Birgit Bossenmaier
Journal: Cancer Research (2013)

Abstract The EGF receptor (EGFR) HER3 is emerging as an attractive cancer therapeutic target due to its central position in the HER receptor signaling network. HER3 amplifies phosphoinositide 3-kinase (PI3K)–driven tumorigenesis and its upregulation in response to other anti-HER therapies has been implicated in resistance to them. Here, we report the development and characterization of RG7116, a novel anti-HER3 monoclonal antibody (mAb) designed to block HER3 activation, downregulate HER3, and mediate enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) via glycoengineering of the Fc moiety. Biochemical studies and X-ray crystallography revealed that RG7116 bound potently and selectively to domain 1 of human HER3. Heregulin binding was prevented by RG7116 at concentrations more than 1 nmol/L as was nearly complete inhibition of HER3 heterodimerization and phosphorylation, thereby preventing downstream AKT phosphorylation. In vivo RG7116 treatment inhibited xenograft tumor growth up to 90% relative to controls in a manner accompanied by downregulation of cell surface HER3. RG7116 efficacy was further enhanced in combination with anti-EGFR (RG7160) or anti-HER2 (pertuzumab) mAbs. Furthermore, the ADCC potency of RG7116 was enhanced compared with the nonglycoengineered parental antibody, both in vitro and in orthotopic tumor xenograft models, where an increased median survival was documented. ADCC degree achieved in vitro correlated with HER3 expression levels on tumor cells. In summary, the combination of strong signaling inhibition and enhanced ADCC capability rendered RG7116 a highly potent HER3-targeting agent suitable for clinical development. Cancer Res; 73(16); 5183–94. ©2013 AACR.
Role of affective associations in the planning and habit systems of decision-making related to addiction
Authors: Marc T. Kiviniemi, Rick A. Bevins
Journal: Behavioral and Brain Sciences (2008)

Abstract The model proposed by Redish et al. considers vulnerabilities within decision systems based on expectancy-value assumptions. Further understanding of processes leading to addiction can be gained by considering other inputs to decision-making, particularly affective associations with behaviors. This consideration suggests additional decision-making vulnerabilities that might explain addictive behaviors.