tbuckley/cabot-search huggingface dataset:
Obesity Contributes to Ovarian Cancer Metastatic Success through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages
Authors: Yueying Liu, Matthew N. Metzinger, Kyle A. Lewellen, Stephanie N. Cripps, Kyle D. Carey, Elizabeth I. Harper, Zonggao Shi, Laura Tarwater, Annie Grisoli, Eric Lee, Ania Slusarz, Jing Yang, Elizabeth A. Loughran, Kaitlyn Conley, Jeff J. Johnson, Yuliya Klymenko, Lana Bruney, Zhong Liang, Norman J. Dovichi, Bentley Cheatham, W. Matthew Leevy, M. Sharon Stack
Journal: Cancer Research (2015)

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy, with high mortality attributable to widespread intraperitoneal metastases. Recent meta-analyses report an association between obesity, ovarian cancer incidence, and ovarian cancer survival, but the effect of obesity on metastasis has not been evaluated. The objective of this study was to use an integrative approach combining in vitro, ex vivo, and in vivo studies to test the hypothesis that obesity contributes to ovarian cancer metastatic success. Initial in vitro studies using three-dimensional mesomimetic cultures showed enhanced cell-cell adhesion to the lipid-loaded mesothelium. Furthermore, in an ex vivo colonization assay, ovarian cancer cells exhibited increased adhesion to mesothelial explants excised from mice modeling diet-induced obesity (DIO), in which they were fed a "Western" diet. Examination of mesothelial ultrastructure revealed a substantial increase in the density of microvilli in DIO mice. Moreover, enhanced intraperitoneal tumor burden was observed in overweight or obese animals in three distinct in vivo models. Further histologic analyses suggested that alterations in lipid regulatory factors, enhanced vascularity, and decreased M1/M2 macrophage ratios may account for the enhanced tumorigenicity. Together, these findings show that obesity potently affects ovarian cancer metastatic success, which likely contributes to the negative correlation between obesity and ovarian cancer survival.
Pertussis Toxin Shows Distinct Early Signalling Events in Platelet-Activating Factor–, Leukotriene B4–, and C5a-Induced Eosinophil Homotypic Aggregation In Vitro and Recruitment In Vivo
Authors: Mauro M. Teixeira, Mark A. Giembycz, Mark A. Lindsay, Paul G. Hellewell
Journal: Blood (1997)
Flexible bronchoscope in pediatrics: Other uses
Authors: Pilar Caro-Aguilera, Estela Perez-Ruiz, Javier Perez-Frias, Lorena Moreno-Requena, Javier Rivas, Dolores Argos
Journal: European Respiratory Journal (2011)

Introduction:  Nutrition supplied through enteral route is of greater benefit to preterm newborn than that supplied through parenteral administration. The insertion of a nasogastric tube (NGT) can occasionally be problematic. Several methods and maneuvers have been described for difficult insertion, but all of them refered to anaesthetized or unconscious patient. We present the case of a NGT insertion assisted by a flexible bronchoscope in a preterm infant.   Case report:  A seven-days old female infant, born at 29 weeks gestation and 979 gr of weigh, was hospitalized in the neonatal intensive care unit (NICU) as she suffered an hyaline membrane disease. She needed mechanical ventilation and enteral nutrition through a NGT. It was not possible to introduce the NGT with the standard procedure. After repeated failures of NGT placement and a mayor complication –pneumothorax-, the neonatologist asked the paediatric pulmonology unit for help as the gastroenterology unit could not help them because their smallest gastroscope was 4.9mm diameter. We used the 2.8mm diameter bronchoscope to go through the esophagus to the stomach. Then we passed a guide through the working channel. After that we removed the bronchoscope maintaining the guide in the stomach. Finally the guide was used to introduce the NGT. We checked the NGT placement with a X-Ray and it was in the correct position.   Conclusion:  NGT is commonly used in NICU. Accurate tube placement is important to ensure a safe and effective enteral feeding. Literature describes misplacement of NGT including its location in the respiratory tract and pleural space, upper oesophagus, or past the pylorus. The introduction aided with an endoscopy visualization can avoid these complications.
Prognostic significance of perirenal fat invasion and tumor size in pT1 to pT3a renal cell carcinoma: Results of a comprehensive multicenter study of the CORONA project—Can we improve prognostic discrimination of patients with stage pT3a tumors?
Authors: Sabine Doris Brookman-May, Matthias May, Richard Zigeuner, Luca Cindolo, Shahrokh F. Shariat, Manfred Wirth, Sven Gunia
Journal: Journal of Clinical Oncology (2015)

416 Background: The renal cell carcinoma (RCC) TNM system merges perirenal fat invasion (PFI) and renal vein invasion (RVI) as stage pT3a despite limited evidence concerning their prognostic equivalence. Additionally, the prognostic value of PFI compared to pT1-pT2 tumors remains controversial. Methods: Data of 7,595 pT1a-pT3a RCC patients undergoing radical nephrectomy or nephron-sparin surgery were pooled from 12 European and U.S. centers (1999-2010). Patients were grouped according to stages and presence of PFI/RVI, i.e., pT1-2N0M0 (n=6,137; 80.8%), pT3aN0M0+PFI (n=1,036; 13.6%), and pT3aN0M0 (RVI±PFI; n=422; 5.6%). Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Univariate and multivariable Cox proportional-hazards regression models, sensitivity and discrimination analyses were conducted to evaluate the impact of clinico-pathological parameters on cancer-specific mortality (CSM). Results: Compared to stage pT1-2, patients staged pT3a were significantly more frequently male (58.9 vs. 53.1%), older (65 vs. 62.1 yrs), more often had clear cell RCC (86.1 vs. 77.7%), Fuhrman grade 3-4 (30.5 vs. 13.4%), tumor size &gt;7 cm (39.6% vs. 13%), and less often underwent NSS (7.1 vs. 36.6%; each p&lt;0.001). On multivariable analysis, CSM of both patients with PFI and RVI±PFI was significantly enhanced compared to pT1-2 patients (HR 1.96 and 2.14, resp.; p&lt;0.001), whereas patients featuring PFI only and RVI±PFI did not differ (HR 0.92; p=0.48). Tumor size instead significantly influenced CSM in stage pT3a (HR 1.07; p&lt;0.001) with a 7 cm cut-off yielding the highest c-index. Conclusions: Since the prognostic impact of PFI and RVI on CSM seems to be comparable, merging both as stage pT3a might be justified. Enhanced prognostic discrimination of stage pT3a RCC patients appears to be possible by employing a 7 cm tumor size cut-off within an alternative staging system.
Teen-Age Alcoholism, Medicine, and the Law
Authors: Ralph S. Ryback
Journal: New England Journal of Medicine (1975)

There is an increasing prevalence of teen-agers who drink alcohol regularly. Half America's high-school students (representing all levels of scholastic achievement and aspiration) go to drinking parties at least once a month and a majority of that group — 61 per cent — admit to getting drunk once a month, according to a study recently released by the National Highway Traffic Safety Administration.1 As each state lowers the purchase age, there is an increasing incidence of new young drinkers who are usually not learning to drink in a controlled, constructive manner from their peers. It rationally follows that with an . . .
Widespread distribution of deletions of the bgl operon in natural isolates of Escherichia coli.
Authors: B G Hall
Journal: Molecular Biology and Evolution (1988)

A deletion that includes the bgl (beta-glucoside utilization) operon of Escherichia coli was originally detected in several rarely occurring natural isolates that utilize cellobiose. Here I show that bgl deletions are present in 95% of the Cel+ isolates obtained from diverse sources. They are also present in 29% of the Cel- strains in two different collections of natural isolates of E. coli. At least three versions of bgl deletions are present in E. coli populations. In the most common version approximately 8 kb of DNA around the bgl region of E. coli K12 is replaced by a specific 6.5-kb DNA fragment. In another version a deletion of similar length is not replaced by the same sequence. A third version involves deletion of approximately 14 kb without the replacement fragment being present. The distribution of these deletions suggests that the version 1 deletion occurred very early in the history of E coli. It also appears likely that there is selection for bgl deletions in Cel+ strains of E. coli. The presence of the version 1 deletion within distantly related phylogenetic groups of E. coli provides evidence for recombination within natural populations of E coli.
Treasury bails out England’s health department
Authors: Anne Gulland
Journal: BMJ (2016)

The UK Treasury has been forced to bail out the Department of Health for England with a £205m (€260m; $300m) cash injection for the 2015-16 financial year.

This means that the department’s budget for the year will rise from £98.7bn to £98.9bn. The Treasury, which announced the increase in funding as part of its annual supplementary estimates, blamed the extra funding on a shortfall in the Pharmaceutical Price Regulation Scheme …
Changes in Zinc Transporter 8 Autoantibodies Following Type 1 Diabetes Onset: The Type 1 Diabetes Genetics Consortium Autoantibody Workshop
Authors: Janet M. Wenzlau, Lisa M. Frisch, John C. Hutton, Pamela R. Fain, Howard W. Davidson
Journal: Diabetes Care (2015)

Zinc transporter 8 autoantibodies (ZnT8A) were analyzed in sera from 1,504 subjects as part of the Type 1 Diabetes Genetics Consortium (T1DGC) Autoantibody Workshop. For these participants with type 1 diabetes (T1D), samples were collected within 3 years of T1D diagnosis. ZnT8A were detected in 862 subjects (57.3%), with the highest frequencies and median titers being associated with the shortest duration of disease. ZnT8A were present at similar frequencies in non-Hispanic whites, non-Hispanic blacks, and Hispanics, but significantly less prevalent in those of Asian ancestry. Sera containing ZnT8A selectively recognizing at least one of the SLC30A8 single nucleotide polymorphisms (encoding ZnT8A) were detected in all populations; however, Trp-specific sera were much less frequent in non-Hispanic blacks, consistent with the anticipated lower frequency of the SLC30A8 rs13266634 T allele in African American populations. ZnT8A positivity was associated with HLA-DQ8, but this was primarily due to the DRB1*0404-DQ8 haplotype. This was in contrast to autoantibodies to IA-2 that were strongly associated with DRB1*0401-DQ8. These effects appeared essentially independent of racial or ethnic background. The DRB1*0401-DQ8 and DRB1*0404-DQ8 haplotypes were associated with T1D subjects positive for GAD65, IA-2, and ZnT8A. In contrast to DRB1*0401-DQ8, there was no significant association of DRB1*0404-DQ8 with single or dual autoantibody positivity. The DRB1*0404-DQ8 haplotype was also associated with T1D subjects whose sera recognized both polymorphic variants of zinc transporter 8, an effect not seen for DRB1*0401-DQ8.
The Membrane Actions of Anesthetics and Tranquilizers
Authors: Philip Seeman
Journal: Pharmacological Reviews (1972)

A diagrammatic summary of the membrane actions of anesthetics and tran-quilizers is shown in figure 15. According to the definition of an anesthetic as a drug which directly blocks the membrane action potential, without appreciably affecting the resting potential, a wide variety of lipid-soluble compounds may be considered as anesthetics. Under conditions of general anesthesia the membrane concentration of an anesthetic is 0.003 moles/kg dry membrane, the anesthetic occupying a volume of 0.02% in the membrane phase. Under conditions of local anesthesia the membrane concentration is 0.04 moles/kg membrane, with an occupying volume of 0.3% in the membrane. The partitioning into the membrane is about 1/10 that of olive oil and about ⅕ that of octanol. These figures hold for many nerve-blocking drugs, and in order to explain differences in the in vivo action of these drugs, other factors must be considered, such as anesthetic sensitization etc. The biomembranes expand or swell about 10 times more than the anesthetic volume of occupation in the membrane, 0.4% expansion occuring under conditions of general anesthesia, and 2 to 3% expansion occuring under conditions of local anesthesia. Although the anesthetics electrically stabilize the membrane, they fluidize and disorder the components within the membrane, probably including membrane water. As a consequence of membrane expansion, membrane-associated enzymes and proteins can be either stimulated or inhibited. The pathways for facilitated fluxes of solutes across membranes are invariably depressed, presumably because of the conformation changes brought about by the membrane-expanding anesthetics; the Na+-conductance channel of the action potential appears to be one of these facilitated pathways. The anesthetic amines displace membrane-bound Ca++ and generally depress passive fluxes of cations. The neutral anesthetics generally increase membrane-bound Ca++ and generally increase the passive fluxes. The membrane fluidization may explain the enhanced neurosecretion of membrane-bound materials, by a mechanism of membrane-membrane fusion.
Phase I and pharmacokinetic study of E7070, a novel sulfonamide, given at a daily times five schedule in patients with solid tumors. A study by the EORTC-Early Clinical Studies Group (ECSG)
Authors: C.J.A. Punt, P. Fumoleau, B. van de Walle, M.N. Faber, M. Ravic, M. Campone
Journal: Annals of Oncology (2001)
Cetuximab as second-line therapy in patients with metastatic esophageal cancer: A phase II Southwest Oncology Group Study
Authors: P. J. Gold, B. Goldman, S. Iqbal, L. P. Leichman, H. J. Lenz, C. D. Blanke
Journal: Journal of Clinical Oncology (2008)

4536 Background: Survival for patients (pts) with metastatic esophageal cancer is poor, with no established therapy for patients failing first-line treatment. Esophageal adenocarcinoma over-expresses the epidermal growth factor receptor (EGFR), providing the rationale for examining the use of the anti-EGFR monoclonal antibody cetuximab. Methods: This was a multicenter, open-label phase II study of single agent cetuximab in pts with metastatic esophageal adenocarcinoma who had failed one prior chemotherapy regimen for advanced disease. Prior (neo) adjuvant therapy was allowed, but prior treatment targeting the EGFR pathway was not. Adequate organ function and Zubrod performance status of 0–2 were required. Pts received cetuximab 400 mg/m2 IV on week one, and 250 mg/m2 IV weekly thereafter. Pts were evaluated for toxicity weekly and for response every 8 weeks. The primary endpoint was a six-month overall survival rate > 40%. Secondary endpoints included progression-free survival, response rate, and toxicity. Tumor tissue was collected for correlative studies. Results: 63 pts were registered, 8 were not eligible. 55 eligible pts (male=49, female=6), median age 61.2 years (range 30.7–88.5) were enrolled. Out of 55 eligible and evaluable pts, 20 survived > 6 months for a 6-month overall survival rate of 36% (95% CI: 24%, 50%). The median overall survival was 4 months (95% CI: 3.2, 5.9), and the median progression-free survival was 1.8 months (95% CI: 1.7, 1.9). There were 3 unconfirmed partial responses. Two pts experienced Grade 4 fatigue, and there was one treatment-related death due to pneumonitis. Four pts had Grade 3 rash, and three of them survived > 6 months. Conclusions: This trial did not meet the primary objective of 23 pts surviving beyond 6 months, and thus cetuximab alone cannot be recommended in the second-line treatment of metastatic esophageal cancer. However, the regimen was associated with a 36% 6-month survival rate, and it was well tolerated. Trials combining cetuximab with cytotoxic chemotherapy in metastatic esophageal cancer are reasonable, and several are in development. Correlative science data from S0415 will be available in June. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone
BMI and risk for death in COPD
Authors: Berne Eriksson, Eva Rönmark, Anne Lindberg, Hana Müllerova, Bo Lundbäck
Journal: European Respiratory Journal (2011)

Background:  Low BMI in COPD is associated with a poor prognosis in clinical settings although nutritional support shows no effect on improving anthropometric measures, lung function, or functional exercise capacity among patients with stable COPD.   Aim:  To study the long-term outcome of BMI-levels in a cohort of COPD subjects derived from a study of the general population.   Methods:  A stratified sample of subjects from a population survey was invited to clinical examinations including lung function tests in 1986. Out of 1506 (91% of the invited) we identified 266 subjects, 64% men, fulfilling the spirometric GOLD criteria of COPD. The subjects with COPD reflected well COPD in the society. The subjects were followed-up to 20 years or until death. Risks for death of these subjects were determined by survival analysis (Cox regression) adjusting for baseline sex, age, heart disease, smoking habits and BMI.   Results:  After 20 years, 46% of the COPD cohort was still alive. At baseline, underweight (BMI   Conclusion:  Mortality in COPD seems to be associated with heart disease where overweight is a risk factor. In a long-term perspective, low BMI was not associated with increased mortality.
Identification of prognostically-relevant signature genes differentially expressed between primary colorectal carcinoma and hepatic metastasis
Authors: A. Y. Lin, M. Chua, Y. L. Choi, W. Yeh, Y. H. Kim, R. Azzi, S. K. So, J. R. Pollack
Journal: Journal of Clinical Oncology (2007)

4116 Background: Colorectal cancer (CRC) is the third most common cancer in the US. Hepatic metastasis (HM), the most common distant metastasis from CRC and occurring in about 60% of CRC patients during the course of their treatment, is a significant clinical problem. Although several clinical prognostic factors for HM from CRC have been identified, little is known about its molecular aspect. Methods: Under IRB approved protocols, we profiled gene expression in a set of 30 specimens from primary CRC and 31 unmatched specimens of HM from CRC. To survey the molecular variations between the two groups, we used cDNA microarrays containing ∼22,000 human genes, and identified differentially expressed genes using the Significance Analysis of Microarrays (SAM) method. To further characterize the clinical relevance of differentially expressed genes, we used immunohistochemistry (IHC) on tissue microarrays of tumor tissues obtained from an independent dataset of 154 patients with primary CRC. Results: Supervised analysis using SAM identified &gt;200 genes with significantly higher expression in HM from CRC compared to primary CRC (and also compared to normal liver), with a false discovery rate (FDR) of &lt;1%. IHC staining of two highly ranked differentially expressed signature genes, SPP1 (osteopontin) and LEF1 (lymphoid enhancer factor-1; a transcriptional mediator of Wnt pathway activation), showed protein overexpression (OE) in 60% and 44% of CRC cases, respectively; with a significant correlation with liver involvement in LEF1 expression (chi-square p=0.04) vs. SPP1 OE (p=0.14). Kaplan Meier analysis revealed significantly worsening survival in patients with LEF1 OE (p&lt;0.01), but not SPP1 (p=0.14). Multivariate analysis identified several relevant prognostic markers: stage (p&lt;0.001), nodal status (p &lt;0.01) and LEF1 OE (p=0.02). Conclusions: Among signature genes differentially expressed between CRC and HM, we demonstrate LEF1, not SPP1, OE to be a poor prognostic factor for survival. Further studies are needed to characterize other signature genes, and to refine our understanding of the role of altered LEF1 expression in CRC tumorigenesis. No significant financial relationships to disclose.
Neutrophil/Lymphocyte Ratio and Piastrinosis Correlate with Clinical Outcome in Metastatic Colorectal Cancer Patients Receiving Regorafenib
Authors: R. Giampieri, M. l De Prete, F. Loupakis, L. Salvatore, T. Prochilo, L. Faloppi, G. Aprile, M. Bianconi, A. Bittoni, A. Falcone, A. Zaniboni, M. Scartozzi, S. Cascinu
Journal: Annals of Oncology (2014)
Multiple tension pneumatocele due to necrotising pneumonia
Authors: Serife Tuba Liman, Aykut Eliçora, Asli Gül Akgül, Salih Topçu, Seymur Salih Mehmetoglu, Serkan Özbay, Zeynep Seda Uyan
Journal: European Respiratory Journal (2013)

Introduction: Pneumatoceles are thin-walled cystic lesions of lung parenchyma. They may be developed after inflammation or injury. They regress after treatment of underlying disease. Necrotising pneumonia is one of the reasons. In childhood, pneumonia may cause pneumatoceles. Tension pneumatocele may be developed with respiratory and cardiovasculary collapse.  Case: Four-year-old boy under treatment of stafilococcus aureus pneumonia was consulted us. Large air-filled multiple cystic lesions were detected compressing the lung.  After a small catheter insertion in one of the cystic lesions, the patient got worse. Other cystic lesions were getting larger radiologically, tension was developed and lesions compressed heart also.  A second catheter was inserted in the upper lesion. Respiratory symptoms were improved, mediastinal shift regressed.  Discussion: Percutaneous decompression may be recommended for single symptomatic pneumatoceles while resection is recommended for symptomatic ones. Because of higher mortality and morbidity rates with surgical management, we think that multiple attempts to percutaneous decompression can be successful and should be tried first.
HIF2 α Is an Essential Molecular Brake for Postprandial Hepatic Glucagon Response Independent of Insulin Signaling
Authors: Sadeesh K. Ramakrishnan, Huabing Zhang, Shogo Takahashi, Brook Centofanti, Sarvesh Periyasamy, Kevin Weisz, Zheng Chen, Michael D. Uhler, Liangyou Rui, Frank J. Gonzalez, Yatrik M. Shah
Journal: Cell Metabolism (2016)