tbuckley/cabot-search huggingface dataset:
Aggressive Surgical Policies in a Retrospectively Reviewed Single-Institution Case Series of Retroperitoneal Soft Tissue Sarcoma Patients
Authors: Alessandro Gronchi, Salvatore Lo Vullo, Marco Fiore, Chiara Mussi, Silvia Stacchiotti, Paola Collini, Laura Lozza, Elisabetta Pennacchioli, Luigi Mariani, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2008)

To explore whether the adoption of a systematic attempt to perform wider resections may lead to prognostic improvements in retroperitoneal soft tissue sarcoma (RSTS).Two hundred eighty-eight consecutive patients who were surgically treated at a single referral center were analyzed. Because a shift toward a systematic, more aggressive surgical approach (ie, liberal en bloc resection of adjacent organs) was in place from 2002 onward, patients were divided in two groups accordingly. Overall survival, crude cumulative incidence (CCI) of local recurrence, and distant metastases were estimated. Univariable and multivariable analyses were carried out.Patients who underwent operation in the early period had a 5-year local recurrence rate of 48% compared with 28% for patients who were treated in the recent period. The number of distant metastases was greater in the recent group (22% v 13%), and overall survival was similar. In addition to the period of treatment, important independent determinants for local recurrence-free survival were histologic grade, histologic subtype, and radiation therapy. Overall, liposarcomas and grades 1 to 2 tumors had the greatest local benefit at 5 years.In a single institution, the adoption of a policy of more liberal visceral en bloc resections was paralleled by greater local control. This benefit might translate into a prognostic improvement only on a longer follow-up for patients with a more indolent disease, whereas systemic failures seem to be the main problem in high-grade tumors. Radiation therapy could add some additional benefit to local outcome and possibly to survival.
Immediate Versus Deferred Hormonal Treatment for Patients With Prostate Cancer Who Are Not Suitable for Curative Local Treatment: Results of the Randomized Trial SAKK 08/88
Authors: Urs E. Studer, Dieter Hauri, Silvia Hanselmann, Dominique Chollet, Hans-Jürg Leisinger, Thomas Gasser, Edgar Senn, Felix B. Trinkler, Reto M. Tscholl, George N. Thalmann, Daniel Dietrich
Journal: Journal of Clinical Oncology (2004)

To determine if immediate hormonal therapy is advantageous compared with deferred treatment in newly diagnosed asymptomatic prostate cancer patients who, for any reason, were not candidates for curative local treatment.Between February 1988 and February 1992, 197 patients with a median age of 76 years (range, 56 to 86 years) were randomly assigned to receive either immediate or deferred orchiectomy on symptomatic progression. The two groups did not differ significantly in clinical or laboratory parameters; 67% had T3-4 tumors and 20% had lymph node metastases. Patient accrual was stopped prematurely because of a similar competing trial. Therefore, observation time was prolonged to achieve the desired number of events and statistical power.Deferred orchiectomy was necessary in 58% of the patients. Median time to disease progression was 2.8 years less than for patients with immediate orchiectomy. However, overall pain-free time from random assignment to symptomatic progression after immediate or deferred orchiectomy, and performance status, were identical in both groups. Cancer-specific survival tended to be longer in the immediate group (P = .09) but there was no difference in overall survival between the two groups (P = .96). The median hemoglobin value decreased significantly after immediate orchiectomy (P < .001).For elderly, asymptomatic patients not undergoing curative local treatment, we were unable to show any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival in our limited number of patients. Disabling complications were prevented in the deferred-treatment arm by careful follow-up; 42% of these patients never required any tumor-specific treatment.
Endocrinology of menopause
Authors: Beatrice J. Edwards, Jin Li
Journal: Periodontology 2000 (2012)

Abstract Menopause is a natural process that occurs in women’s lives as part of normal aging. Many women go through the menopausal transition with few or no symptoms, while some have significant, or even disabling, symptoms. This manuscript reviews the physiologic processes and symptoms connected with menopause and the diseases associated with menopause, as well as how menopausal symptoms are managed.
Picoeukaryotic sequences in the Sargasso Sea metagenome
Authors: Gwenael Piganeau, Yves Desdevises, Evelyne Derelle, Herve Moreau
Journal: Genome biology (2008)

With genome sequencing becoming more and more affordable, environmental shotgun sequencing of the microorganisms present in an environment generates a challenging amount of sequence data for the scientific community. These sequence data enable the diversity of the microbial world and the metabolic pathways within an environment to be investigated, a previously unthinkable achievement when using traditional approaches. DNA sequence data assembled from extracts of 0.8 microm filtered Sargasso seawater unveiled an unprecedented glimpse of marine prokaryotic diversity and gene content. Serendipitously, many sequences representing picoeukaryotes (cell size <2 microm) were also present within this dataset. We investigated the picoeukaryotic diversity of this database by searching sequences containing homologs of eight nuclear anchor genes that are well conserved throughout the eukaryotic lineage, as well as one chloroplastic and one mitochondrial gene.We found up to 41 distinct eukaryotic scaffolds, with a broad phylogenetic spread on the eukaryotic tree of life. The average eukaryotic scaffold size is 2,909 bp, with one gap every 1,253 bp. Strikingly, the AT frequency of the eukaryotic sequences (51.4%) is significantly lower than the average AT frequency of the metagenome (61.4%). This represents 4% to 18% of the estimated prokaryotic diversity, depending on the average prokaryotic versus eukaryotic genome size ratio.Despite similar cell size, eukaryotic sequences of the Sargasso Sea metagenome have higher GC content, suggesting that different environmental pressures affect the evolution of their base composition.
Androgen Receptor Splice Variants Dimerize to Transactivate Target Genes
Authors: Duo Xu, Yang Zhan, Yanfeng Qi, Bo Cao, Shanshan Bai, Wei Xu, Sanjiv S. Gambhir, Peng Lee, Oliver Sartor, Erik K. Flemington, Haitao Zhang, Chang-Deng Hu, Yan Dong
Journal: Cancer Research (2015)

Abstract Constitutively active androgen receptor splice variants (AR-V) lacking the ligand-binding domain have been implicated in the pathogenesis of castration-resistant prostate cancer and in mediating resistance to newer drugs that target the androgen axis. AR-V regulates expression of both canonical AR targets and a unique set of cancer-specific targets that are enriched for cell-cycle functions. However, little is known about how AR-V controls gene expression. Here, we report that two major AR-Vs, termed AR-V7 and ARv567es, not only homodimerize and heterodimerize with each other but also heterodimerize with full-length androgen receptor (AR-FL) in an androgen-independent manner. We found that heterodimerization of AR-V and AR-FL was mediated by N- and C-terminal interactions and by the DNA-binding domain of each molecule, whereas AR-V homodimerization was mediated only by DNA-binding domain interactions. Notably, AR-V dimerization was required to transactivate target genes and to confer castration-resistant cell growth. Our results clarify the mechanism by which AR-Vs mediate gene regulation and provide a pivotal pathway for rational drug design to disrupt AR-V signaling as a rational strategy for the effective treatment of advanced prostate cancer. Cancer Res; 75(17); 3663–71. ©2015 AACR.
A Factor Underlying Late-Phase Arrhythmogenicity After Cell Therapy to the Heart
Authors: Steven R. Coppen, Satsuki Fukushima, Yasunori Shintani, Kunihiko Takahashi, Anabel Varela-Carver, Husein Salem, Kenta Yashiro, Magdi H. Yacoub, Ken Suzuki
Journal: Circulation (2008)

Background— Arrhythmia occurrence is a variable but serious concern of cell therapy for treating heart failure. Using a rat postinfarction chronic heart failure model, we compared skeletal myoblast (SMB) with bone marrow cell (BMC) injection to highlight donor cell-specific, late-phase arrhythmogenesis and the underlying factors. Methods and Results— SMBs or BMCs derived from male GFP-transgenic rats, or PBS were injected intramyocardially into female rat hearts 3 weeks after coronary artery occlusion. At 28 days after injection, echocardiography showed that the left ventricular ejection fraction was significantly improved in both the SMB and BMC groups, compared to PBS control despite poor graft survival as assessed by PCR for the male-specific gene. Radio-telemetry analysis revealed that the SMB group displayed a higher occurrence of ventricular premature contractions with an elongation of the QRS complex and the hearts were more susceptible to isopreterenol-induced ventricular tachycardia compared to the BMC and PBS groups. Western blot and immunoconfocal analysis showed that the gap junction protein, connexin43, was widely and persistently decreased in the SMB group compared to the other groups. IL-1β was shown to be upregulated in hearts after SMB injection, and in vitro experiments demonstrated that exposure to IL-1β caused a decrease in connexin43 and intercellular communication in cultured cardiomyocytes. Conclusions— Although cell therapy was capable of improving function of the postinfarction chronically failing heart, there was late-phase arrhythmogenicity specific to donor cell type. Global downregulation of connexin43 in the host myocardium was indicated to be an important factor underlying late-phase arrhythmogenicity after SMB transplantation.
Increased serum concentrations of tissue inhibitor of metalloproteinase-1 in COPD patients
Authors: Y. Higashimoto, Y. Yamagata, T. Iwata, M. Okada, T. Ishiguchi, H. Sato, M. Masuda, H. Itoh
Journal: European Respiratory Journal (2005)

Matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase (TIMP)-1 concentrations are increased in the sputum of asthma and chronic bronchitis patients, and are thought to be related to airflow obstruction. However, serum concentrations of these enzymes have not been clearly evaluated in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to examine the serum concentrations of these enzymes in COPD and asthmatic patients in order to determine their relationship with airway obstruction. Serum samples were obtained from 72 patients with COPD: 66 control subjects and 26 patients with asthma. Smoking histories of control subjects were matched with those of COPD patients. Serum concentrations of TIMP-1 and MMP-9 were determined by ELISA. The circulating TIMP-1 concentration was significantly higher in stable COPD patients than in control and asthmatic subjects, and was significantly negatively correlated with forced expiratory volume in one second/forced vital capacity in COPD patients. The molar ratio between MMP-9 and TIMP-1 was significantly lower in COPD patients than in control subjects. In patients with COPD, the serum TIMP-1 concentration was significantly increased during disease exacerbation. In conclusion, the current findings suggest that serum tissue inhibitors of metalloproteinase-1 concentration can be used as a serum marker of airway obstruction and exacerbation in chronic obstructive pulmonary disease patients.
Spinnaker Formation of Sinus Venosus Valve
Authors: RONALD N. JONES, NELSON R. NILES
Journal: Circulation (1968)

A persistent right valve of the sinus venosus fatally complicated a case of tricuspid atresia in a 10-year-old boy. The center of this large membrane stretched to form a sac resembling a spinnaker. Depending on the relative amounts and directions of blood flowing against it from the coronary sinus below and the venae cavae above, the sail might fill or empty quickly. This gave means of potential obstruction: either of coronary venous flow which, without a tricuspid valvular orifice, could be trapped beneath the membrane; or of all right atrial flow if the sac fell across the sole atrial outlet, the septal defect. Such episodic block caused syncope six times in the last 23 months of life and death in acute right heart failure.
Limited Resection Versus Lobectomy for Older Patients With Early-Stage Lung Cancer: Impact of Histology
Authors: Rajwanth R. Veluswamy, Nicole Ezer, Grace Mhango, Emily Goodman, Marcelo Bonomi, Alfred I. Neugut, Scott Swanson, Charles A. Powell, Mary B. Beasley, Juan P. Wisnivesky
Journal: Journal of Clinical Oncology (2015)

Limited resection has been increasingly used in older patients with stage IA lung cancer. However, the equivalency of limited resection versus lobectomy according to histology is unknown.We identified patients older than 65 years with stage IA invasive adenocarcinoma or squamous cell carcinoma ≤ 2 cm who were treated with limited resection (wedge or segmentectomy) or lobectomy in the Surveillance, Epidemiology, and End Results-Medicare database. We estimated propensity scores that predicted the use of limited resection and compared survival of patients treated with limited resection versus lobectomy. Treatments were considered equivalent if the upper 95th percentile of the hazard ratio (HR) for limited resection was ≤ 1.25.Overall, 27% of 2,008 patients with adenocarcinoma and 32% of 1,139 patients with squamous cell carcinoma underwent limited resection. Survival analyses, adjusted for propensity score by using inverse probability weighting, showed that limited resection was not equivalent to lobectomy in patients with adenocarcinoma (HR, 1.21; upper 95% CI,1.34) or squamous cell carcinoma (HR, 1.21; upper 95% CI, 1.39). Although patients with adenocarcinomas treated with segmentectomy had equivalent survival rates to those treated with lobectomy (HR, 0.97; upper 95% CI, 1.07), outcomes of those treated with wedge resection (HR, 1.29; upper 95% CI, 1.42) did not. Among patients with squamous cell carcinoma, neither wedge resection (HR, 1.34; upper 95% CI, 1.53) nor segmentectomy (HR, 1.19; upper 95% CI, 1.36) were equivalent to lobectomy.We found generally that limited resection is not equivalent to lobectomy in older patients with invasive non-small-cell lung cancer ≤ 2 cm in size, although segmentectomy may be equivalent in patients with adenocarcinoma.
Maternal Obesity and Risk of Gestational Diabetes Mellitus
Authors: Susan Y. Chu, William M. Callaghan, Shin Y. Kim, Christopher H. Schmid, Joseph Lau, Lucinda J. England, Patricia M. Dietz
Journal: Diabetes Care (2007)

OBJECTIVE—Numerous studies in the U.S. and elsewhere have reported an increased risk of gestational diabetes mellitus (GDM) among women who are overweight or obese compared with lean or normal-weight women. Despite the number and overall consistency of studies reporting a higher risk of GDM with increasing weight or BMI, the magnitude of the association remains uncertain. This meta-analysis was conducted to better estimate this risk and to explore differences across studies. RESEARCH DESIGN AND METHODS—We identified studies from three sources: 1) a PubMed search of relevant articles published between January 1980 and January 2006, 2) reference lists of publications selected from the PubMed search, and 3) reference lists of review articles on obesity and maternal outcomes published between January 2000 and January 2006. We used a Bayesian model to perform the meta-analysis and meta-regression. We included cohort-designed studies that reported obesity measures reflecting pregnancy body mass, that had a normal-weight comparison group, and that presented data allowing a quantitative measurement of risk. RESULTS—Twenty studies were included in the meta-analysis. The unadjusted ORs of developing GDM were 2.14 (95% CI 1.82–2.53), 3.56 (3.05–4.21), and 8.56 (5.07–16.04) among overweight, obese, and severely obese compared with normal-weight pregnant women, respectively. The meta-regression analysis found no evidence that these estimates were affected by selected study characteristics (publication date, study location, parity, type of data collection [retrospective vs. prospective], and prevalence of GDM among normal-weight women). CONCLUSIONS—Our findings indicate that high maternal weight is associated with a substantially higher risk of GDM.
Dobutamine Improves Liver Function after Hemorrhagic Shock through Induction of Heme Oxygenase-1
Authors: Alexander Raddatz, Darius Kubulus, Johannes Winning, Inge Bauer, Sascha Pradarutti, Beate Wolf, Sascha Kreuer, Hauke Rensing
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Induction of heme oxygenase-1 (HO-1) protects the liver against reperfusion injury after hemorrhagic shock. Previous data suggest that the beta(1)-adrenoceptor agonist dobutamine induces HO-1 in hepatocytes.To investigate the functional significance of dobutamine pretreatment for liver function after hemorrhagic shock in vivo.Anesthetized rats received either Ringer's (Vehicle/Shock), 10 microg/kg/min of the beta(1)-adrenoceptor agonist dobutamine (Dob/Shock), or 10 microg/kg/min dobutamine and 500 microg/kg/min of the beta(1)-adrenoceptor antagonist esmolol (Dob/Esmolol/Shock) for 6 h. Hemorrhagic shock was induced thereafter (mean arterial pressure, 35 mm Hg for 90 min). Animals were resuscitated with shed blood and Ringer's. In addition, the HO pathway was blocked after dobutamine pretreatment with 10 micromol/kg tin-mesoporphyrin-IX (Dob/SnMP/Shock) or animals received 100 mg/kg of the carbon monoxide donor dichloromethane (DCM/Shock).Hepatocellular metabolism and liver blood flow were measured by plasma disappearance rate of indocyanine green (PDR(ICG)) as a sensitive marker of liver function.Pretreatment with dobutamine induced HO-1 in pericentral hepatocytes and improved PDR(ICG) (Vehicle/Shock: 11.7 +/- 8.12%/min vs. Dob/Shock: 19.7 +/- 2.46%/min, p = 0.006). Blockade of the HO pathway after preconditioning and the combined pretreatment with dobutamine and esmolol decreased PDR(ICG) (Dob/SnMP/Shock: 12.6 +/- 4.24%/min, p = 0.011; Dob/Esmolol/Shock: 10.2 +/- 4.34%/min, p = 0.008). Pretreatment with a carbon monoxide donor improved PDR(ICG) (DCM/Shock: 18 +/- 3.19%/min, p = 0.022) compared with Vehicle/Shock.These results suggest a beta(1)-adrenoceptor-dependent hepatic up-regulation of HO-1 and a better maintained hepatocellular function after hemorrhagic shock in animals pretreated with dobutamine. The improved hepatocellular function may be in part mediated by carbon monoxide because of up-regulation of HO-1. Pretreatment with dobutamine might be a potential means of pharmacologic preconditioning before ischemia-reperfusion of the liver.
Cultured human monocytes synthesize and secrete alpha2-macroglobulin.
Authors: T Hovi, D Mosher, A Vaheri
Journal: The Journal of Experimental Medicine (1977)

alpha2-Macroglobulin levels in the supernates of cultures of different subpopulations of human peripheral blood mononuclear leukocytes were assayed by a radioimmunoassay. Unfractionated mononuclear leukocytes produced greater amounts of the macroglobulin (4.0 vs. 0.8 ng/10(6) cells) than did subpopulations enriched in T or B+T lymphocytes, by passage through nylon wool or cotton wool columns, respectively. Still higher concentrations of alpha2-macroglobulin (40 ng/10(6) cells) were measured in the supernates of glass-adherent mononuclear leukocyte cultures. These results suggest that cells of monocyte-macrophage lineage are mainly, if not exclusively, responsible for the appearance of alpha2- macroglobulin in the supernate of human peripheral blood leukocyte cultures. The de novo synthesis and release of alpha2-macroglobulin by cultured monocytes was demonstrated by immunoprecipitation of radioactivity from supernates of 32S-methionine-labeled glass-adherent cells. Antiserum against purified alpha2-macroglobulin was used in both Ouchterlony double diffusion and double antibody precipitation tests. SDS-polyacrylamide gel electrophoresis of immunoprecipitates showed that most of the radioactivity comigrated with authentic alpha2-macroglobulin subunit at about 160,000 daltons.
Targeting of the VHL-Hypoxia-Inducible Factor-Hypoxia-Induced Gene Pathway for Renal Cell Carcinoma Therapy
Authors: Jeffrey A. Sosman
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Treatment of advanced renal cancer has made little progress in the past 30 yr. Most clinical efforts have incorporated cytokine-based therapy. The presumption has been that the cytokines may trigger a host immune response against the renal cancer. Only IFN-α and high-dose IL-2 seemed to have positive effects on patient outcomes. IFN has prolonged the lives of patients by a few months, and high-dose IL-2 is capable of inducing very prolonged remissions (&gt;5 yr) for a small number of patients. Nephrectomy in the presence of metastatic disease has been established as an effective procedure for select patients, providing palliation and prolonging survival. Finally, enthusiasm has focused on the use of nonmyeloablative allogeneic stem cell transplantation and donor leukocyte infusion for the induction of graft versus tumor effects. Early results are both provocative and promising. A number of agents that target the critical gene products downstream from pVHL and hypoxia-inducible factor-1, such as vascular endothelial growth factor, PDGF, EGF receptor, and TGF-α, have recently become available. The new agents are capable of inhibiting specific cellular targets, and the biologic characteristics of clear cell carcinoma of the kidney support their application. If the correct targets are carefully selected for inhibition in tumors in which the targets are present (clear cell histologic features and loss of VHL expression), then results should resemble those others have observed with targeted therapy, such as the use of STI-571 (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ) for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors or anti-HER2/neu (Herceptin; Genentech, South San Francisco, CA) for treatment of breast cancer. E-mail: jeff.sosman@vanderbilt.edu
Inferring the Evolutionary History of Primate microRNA Binding Sites: Overcoming Motif Counting Biases
Authors: Alfred T. Simkin, Jeffrey A. Bailey, Fen-Biao Gao, Jeffrey D. Jensen
Journal: Molecular Biology and Evolution (2014)

The first microRNAs (miRNAs) were identified as essential, conserved regulators of gene expression, targeting the same genes across nearly all bilaterians. However, there are also prominent examples of conserved miRNAs whose functions appear to have shifted dramatically, sometimes over very brief periods of evolutionary time. To determine whether the functions of conserved miRNAs are stable or dynamic over evolutionary time scales, we have here defined the neutral turnover rates of short sequence motifs in predicted primate 3′-UTRs. We find that commonly used approaches to quantify motif turnover rates, which use a presence/absence scoring in extant lineages to infer ancestral states, are inherently biased to infer the accumulation of new motifs, leading to the false inference of continually increasing regulatory complexity over time. Using a maximum likelihood approach to reconstruct individual ancestral nucleotides, we observe that binding sites of conserved miRNAs in fact have roughly equal numbers of gain and loss events relative to ancestral states and turnover extremely slowly relative to nearly identical permutations of the same motif. Contrary to case studies showing examples of functional turnover, our systematic study of miRNA binding sites suggests that in primates, the regulatory roles of conserved miRNAs are strongly conserved. Our revised methodology may be used to quantify the mechanism by which regulatory networks evolve.