tbuckley/cabot-search huggingface dataset:
Activin A impairs insulin action in cardiomyocytes via up-regulation of miR-143
Authors: Marcel Blumensatt, Sabrina Greulich, Daniella Herzfeld de Wiza, Heidi Mueller, Bujar Maxhera, Martijn J. Rabelink, Rob C. Hoeben, Payam Akhyari, Hadi Al-Hasani, Johannes B. Ruige, D. Margriet Ouwens
Journal: Cardiovascular Research (2013)

Enhanced activin A release from epicardial adipose tissue (EAT) has been linked to the development of cardiac dysfunction in type 2 diabetes (T2D). This study examined whether the inhibition of insulin action induced by epicardial adipokines in cardiomyocytes can be ascribed to alterations in miRNA expression.Expression levels of miRNAs were assessed by real-time PCR in primary adult rat cardiomyocytes (ARC) exposed to conditioned media generated from EAT biopsies (CM-EAT) from patients with and without T2D. CM-EAT-T2D altered the expression of eight miRNAs in ARC vs. CM-EAT from patients without T2D. Of these, only expression of the miR-143/145 cluster was affected by activin A in the same direction as CM-EAT-T2D. Accordingly, activin A neutralizing antibodies prevented the induction of the miR-143/145 cluster by CM-EAT-T2D. Subsequently, the impact of the miR-143/145 cluster on insulin action was investigated. Transfection of HL-1 cells with precursor-miR-143 (pre-miR-143), but not pre-miR-145, blunted the insulin-mediated phosphorylation of Akt and its substrate proline-rich Akt substrate of 40 kDa (PRAS40), and reduced insulin-stimulated glucose uptake. Also lentivirus-mediated expression of pre-miR-143 in ARC reduced insulin-induced Akt phosphorylation. These effects were ascribed to down-regulation of the miR-143 target and regulator of insulin action, the oxysterol-binding protein-related protein 8 (ORP8) in both ARC and HL-1 cells. Finally, LNA-anti-miR-143 protected against the detrimental effects of CM-EAT-T2D on insulin action in ARC.Activin A released from EAT-T2D inhibits insulin action via the induction of miR-143 in cardiomyocytes. This miRNA inhibits the Akt pathway through down-regulation of the novel regulator of insulin action, ORP8.
A new bronchoscopic method to measure airway size
Authors: W.V. Dörffel, I. Fietze, D Hentschel, J Liebetruth, Y. Rückert, P. Rogalla, K-D. Wernecke, G. Baumann, C. Witt
Journal: European Respiratory Journal (1999)

Bronchoscopic evaluation of stenosis is limited due to radial distortion of bronchoscopic images and the unknown distance between the endoscope and the stenotic area. The purpose of this study was the development and validation of a method for measuring cross-sectional areas in large airways. Distance measurements were performed using a laser probe inserted into the working channel of a bronchoscope. The laser probe was positioned to the locus of interest in the airway, a ring of light (helium/neon) projected on to the luminal wall and the images acquired using an electronic bronchoscope. The images taken were distortion-corrected by means of a computer program. The method was validated by simulating airways using tubes of known diameter. Additionally, distortion-corrected bronchoscopic images were compared with distortion-free videoscopic image analysis of tracheal slices taken from pigs. In the case of the plastic tubes, Pearson's correlation coefficient (r) as well as the intraclass correlation coefficient (ICC) were slightly higher (r=0.99, p<0.01, ICC=0.97) than the correlation of cross-sectional areas between bronchoscopic and videoscopic images of tracheal slices (r=0.88, p<0.01, ICC=0.87). This concept allows accurate and reproducible determination of cross-sectional areas in large airways.
Estrogen Attenuates Integrin-β <sub>3</sub> –Dependent Adventitial Fibroblast Migration After Inhibition of Osteopontin Production in Vascular Smooth Muscle Cells
Authors: Guohong Li, Yiu-Fai Chen, Stacey S. Kelpke, Suzanne Oparil, John A. Thompson
Journal: Circulation (2000)

Background —Previous in vitro studies have suggested that estrogen attenuates the vascular injury response by modulating vascular smooth muscle cell (VSMC) expression of soluble factor(s) directing migration of adventitial fibroblasts. Previous in vivo studies have established a role for osteopontin (OPN) and its integrin receptors after vascular injury. In this study, we examined OPN expression in activated VSMCs, its modulation by estrogen, and its effects on adventitial fibroblast migration. In addition, the relative functional roles of β 1 - and β 3 -integrin–matrix interactions were examined. Methods and Results —Primary cultures of VSMCs and adventitial fibroblasts were derived from female Sprague-Dawley rats. Serum-activated VSMCs expressed high levels of OPN mRNA and secreted protein that was effectively inhibited by estrogen treatment (10 −7 mol/L). Compared with VSMCs, fibroblasts expressed similar levels of integrins αν and β 1 and higher levels of integrin-β 3 . Exogenous OPN (5.0 to 40 μg/mL) directed fibroblast migration in a dose-dependent fashion. Anti–β 3 -integrin antibody (F11) pretreatment markedly inhibited adventitial fibroblast migration directed by exogenous OPN or VSMC-conditioned medium in a dose-dependent manner. In contrast, anti–β 1 -integrin antibody (Ha2/5) did not affect fibroblast migration. Similarly, pretreatment with either linear or cyclic RGD peptides (10 to 1000 μmol/L) inhibited fibroblast migration directed by OPN or VSMC-conditioned medium in a dose-dependent manner. Conclusions —These observations suggest that estrogen indirectly attenuates integrin-β 3 –dependent adventitial fibroblast migration after inhibition of OPN expression in VSMCs.
Targeting CUB Domain-Containing Protein 1 with a Monoclonal Antibody Inhibits Metastasis in a Prostate Cancer Model
Authors: Amara C. Siva, Martha A. Wild, Richard E. Kirkland, Mary Jean Nolan, Bing Lin, Toshiaki Maruyama, Ferda Yantiri-Wernimont, Shana Frederickson, Katherine S. Bowdish, Hong Xin
Journal: Cancer Research (2008)

Through a whole-cell panning approach, we previously identified a panel of antibodies that bound to prostate cancer cell surface antigens. One such antigen, CUB domain-containing protein 1 (CDCP1), was recognized by monoclonal antibody 25A11 and is a single transmembrane molecule highly expressed in several metastatic cancers as well as on CD34(+)CD133(+) myeloid leukemic blast cells. We show CDCP1 expression on prostate cancer cell lines by real-time quantitative PCR (RT-qPCR), flow cytometry, and immunohistochemistry and on prostate cancer patient samples by RT-qPCR and immunohistochemical staining. In cell-based assays, antibody 25A11 inhibited prostate cancer cell migration and invasion in vitro. Further characterization showed that CDCP1 is internalized on antibody binding. When 25A11 was coupled to the cytotoxin saporin either directly or via a secondary antibody, both resulted in prostate cancer cell killing in vitro. In vivo targeting studies with an anti-CDCP1 immunotoxin showed significant inhibition of primary tumor growth as well as metastasis in a mouse xenograft model. These data provide support for continued evaluation of anti-CDCP1 therapy for potential use in cancer in primary and metastatic disease.
Lung volume calculated from electrical impedance tomography in ICU patients at different PEEP levels
Authors: Ido G. Bikker, Steffen Leonhardt, Jan Bakker, Diederik Gommers
Journal: Intensive Care Medicine (2009)

To study and compare the relationship between end-expiratory lung volume (EELV) and changes in end-expiratory lung impedance (EELI) measured with electrical impedance tomography (EIT) at the basal part of the lung at different PEEP levels in a mixed ICU population.End-expiratory lung volume, EELI and tidal impedance variation were determined at four PEEP levels (15-10-5-0 cm H2O) in 25 ventilated ICU patients. The tidal impedance variation and tidal volume at 5 cm H2O PEEP were used to calculate change in impedance per ml; this ratio was then used to calculate change in lung volume from change in EELI. To evaluate repeatability, EELV was measured in quadruplicate in five additional patients.There was a significant but relatively low correlation (r = 0.79; R2 = 0.62) and moderate agreement (bias 194 ml, SD 323 ml) between DeltaEELV and change in lung volume calculated from the DeltaEELI. The ratio of tidal impedance variation and tidal volume differed between patients and also varied at different PEEP levels. Good agreement was found between repeated EELV measurements and washin/washout of a simulated nitrogen washout technique.During a PEEP trial, the assumption of a linear relationship between change in global tidal impedance and tidal volume cannot be used to calculate EELV when impedance is measured at only one thoracic level just above the diaphragm.
A Critical Subset Model Provides a Conceptual Basis for the High Antiviral Activity of Major HIV Drugs
Authors: Lin Shen, S. Alireza Rabi, Ahmad R. Sedaghat, Liang Shan, Jun Lai, Sifei Xing, Robert F. Siliciano
Journal: Science Translational Medicine (2011)

Disruption of the cooperative action of multiple copies of a drug target explains the high antiviral activity of the most active HIV drugs.
Organic anion transport in HepG2 cells: Absence of the high-affinity, chloride-dependent transporter
Authors: Albert D. Min, Tobias Goeser, Rui Liu, Celeste G. Campbell, Phyllis M. Novikoff, Allan W. Wolkoff
Journal: Hepatology (1991)

In previous studies, we identified a 55 kD organic anion-binding protein in liver cell sinusoidal plasma membrane subfractions. Other investigators identified another 55 kD bromosulfophthalein/bilirubin binding protein on the surface of rat hepatocytes and HepG2 cells and suggested that this protein served as a transporter for these ligands. In this study, transport of 35S-sulfobromophthalein by the human hepatoma cell line, HepG2, was quantified in the presence and absence of bovine serum albumin to further clarify the possible function of these plasma membrane binding proteins. In contrast to results in normal rat hepatocytes, virtually no uptake of 35S-sulfobromophthalein by HepG2 cells in the presence of bovine serum albumin was found. In the absence of albumin, HepG2 cells expressed temperature-dependent uptake of 35S-sulfobromophthalein. However, the high-affinity Cl(-)-dependent sulfobromophthalein transport that characterizes normal rat hepatocytes was absent, as indicated by an approximately 95-fold lower affinity and 170-fold higher capacity of HepG2 cells for sulfobromophthalein compared with previous results with rat hepatocytes. These results suggest that 55 kD sulfobromophthalein/bilirubin-binding protein on the liver cell surface differs from organic anion-binding protein and is not responsible for sulfobromophthalein extraction in the presence of albumin, although it may play some role in lower affinity transport by cells. Immunoblot analysis and metabolic labeling of HepG2 cells demonstrated synthesis of organic anion-binding protein. However, light microscopic immunocytochemistry and immunoprecipitation of surface iodinated rat hepatocytes and HepG2 cells with antibody to a recombinant organic anion-binding protein fusion protein indicated absence of organic anion-binding protein on the surface of HepG2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial
Authors: Raquel González, Ghyslain Mombo-Ngoma, Smaïla Ouédraogo, Mwaka A. Kakolwa, Salim Abdulla, Manfred Accrombessi, John J. Aponte, Daisy Akerey-Diop, Arti Basra, Valérie Briand, Meskure Capan, Michel Cot, Abdunoor M. Kabanywanyi, Christian Kleine, Peter G. Kremsner, Eusebio Macete, Jean-Rodolphe Mackanga, Achille Massougbodgi, Alfredo Mayor, Arsenio Nhacolo, Golbahar Pahlavan, Michael Ramharter, María Rupérez, Esperança Sevene, Anifa Vala, Rella Zoleko-Manego, Clara Menéndez
Journal: PLoS Medicine (2014)

Clara Menéndez and colleagues conducted an open-label randomized controlled trial in HIV-negative pregnant women in Benin, Gabon, Mozambique, and Tanzania to evaluate the safety and efficacy of mefloquine compared to sulfadoxine-pyrimethamine for intermittent preventative therapy for malaria. Please see later in the article for the Editors' Summary
Plasma corticosteroid levels in out-patients treated with topical steroids
Authors: LYN WILSON, D.I. WILLIAMS, STEPHANIE D. MARSH
Journal: British Journal of Dermatology (2006)

Plasma corticosteroid levels in 295 out-patients using halogenated topical steroids were compared with levels in 158 controls. The mean level of the treated patients was 12-5 /(g/ioo ml compared with 14 μg/100 ml in the controls; 96% of the patients who used topical steroids and 99",) of the controls had levels of 6 μg/100 ml or more. Five of the six patients whose plasma corticosteroid levels were less than 5μg/100 ml on first sampling had normal values on retesting after an interval of 2 weeks or more.
Failure of a reinforced triple course of hepatitis B vaccination in patients transplanted for HBV-related cirrhosis
Authors: Mario Angelico, Daniele Di Paolo, Massimo O. Trinito, Alessandra Petrolati, Antonio Araco, Settimio Zazza, Raffaella Lionetti, Carlo U. Casciani, Giuseppe Tisone
Journal: Hepatology (2002)

Long-term immunoprophylaxis with anti-HBs immunoglobulins (HBIg) is used to prevent hepatitis B (HBV) reinfection after liver transplantation for HBV-related cirrhosis. This approach is highly expensive. A recent report proposed posttransplant HBV vaccination with a reinforced schedule as an alternative strategy to allow HBIg discontinuation. We investigated the efficacy of a reinforced triple course of HBV vaccination in 17 patients transplanted for HBsAg—positive cirrhosis 2 to 7 years earlier. The first cycle consisted of 3 double intramuscular doses (40 μg) of recombinant vaccine at month 0, 1, and 2, respectively. This was followed, in nonresponders, by a second cycle of 6 intradermal 10 μg doses every 15 days. All nonresponders then received a third cycle identical to the first one. Vaccination started 4.5 months after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. All patients were seronegative for HBsAg and HBV-DNA (by PCR) and positive for anti-HBe, and 7 were positive for anti-HDV. After the first cycle one patient (#5, 53 years old, male) developed an anti-HBs titer of 154 IU/L, another (#12) reached a titer of 20 IU/L and the remainder had titers &lt;10 IU/L. At month 7, patient #5 reached a titer of 687 IU/L. After the second cycle only one additional patient (#9) had a slight response (an anti-HBs titer of 37 IU/L). After the third cycle patient #9 rose to an anti-HBs titer of 280 IU/L, patient #12 dropped to 10 IU/L, and no other patient responded. In conclusion, a highly reinforced HBV vaccination program is effective only in a few patients who had liver transplants for HBV—related cirrhosis.
Health Status of Air Force Veterans Occupationally Exposed to Herbicides in Vietnam
Authors: William H. Wolfe
Journal: JAMA (1990)

The Air Force Health Study is a 20-year comprehensive assessment of the health of Air Force veterans of Operation Ranch Hand, the unit responsible for aerial spraying of herbicides in Vietnam. The study compares the health and noncombat mortality of Ranch Hand veterans with a comparison group of Air Force veterans primarily involved with cargo missions in Southeast Asia but who were not exposed to herbicides. This report summarizes the health of these veterans as determined at the third in a series of physical examinations. Nine hundred ninety-five Ranch Hands and 1299 comparison subjects attended the second follow-up examination in 1987. The two groups were similar in reported health problems, diagnosed skin conditions, and hepatic, cardiovascular, and immune profiles. Ranch Hands have experienced significantly more basal cell carcinomas than comparison subjects. The two groups were not different with respect to melanoma and systemic cancer. (<i>JAMA</i>. 1990;264:1824-1831)
Cardiac Tissue Engineering in an In Vivo Vascularized Chamber
Authors: Andrew N. Morritt, Susan K. Bortolotto, Rodney J. Dilley, XiaoLian Han, Andrew R. Kompa, David McCombe, Christine E. Wright, Silviu Itescu, James A. Angus, Wayne A. Morrison
Journal: Circulation (2007)

Background— Cardiac tissue engineering offers the prospect of a novel treatment for acquired or congenital heart defects. We have created vascularized pieces of beating cardiac muscle in the rat that are as thick as the adult rat right ventricle wall. Method and Results— Neonatal rat cardiomyocytes in Matrigel were implanted with an arteriovenous blood vessel loop into a 0.5-mL patented tissue-engineering chamber, located subcutaneously in the groin. Chambers were harvested 1, 4, and 10 weeks after insertion. At 4 and 10 weeks, all constructs that grew in the chambers contracted spontaneously. Immunostaining for α-sarcomeric actin, troponin, and desmin showed that differentiated cardiomyocytes present in tissue at all time points formed a network of interconnected cells within a collagenous extracellular matrix. Constructs at 4 and 10 weeks were extensively vascularized. The maximum thickness of cardiac tissue generated was 1983 μm. Cardiomyocytes increased in size from 1 to 10 weeks and were positive for the proliferation markers Ki67 and PCNA. Connexin-43 stain indicated that gap junctions were present between cardiomyocytes at 4 and 10 weeks. Echocardiograms performed between 4 and 10 weeks showed that the tissue construct contracted spontaneously in vivo. In vitro organ bath experiments showed a typical cardiac muscle length-tension relationship, the ability to be paced from electrical field pulses up to 3 Hz, positive chronotropy to norepinephrine, and positive inotropy in response to calcium. Conclusion— In summary, the use of a vascularized tissue-engineering chamber allowed generation of a spontaneously beating 3-dimensional mass of cardiac tissue from neonatal rat cardiomyocytes. Further development of this vascularized model will increase the potential of cardiac tissue engineering to provide suitable replacement tissues for acquired and congenital defects.
Gastropleural fistula due to gastric lymphoma presenting as tension pneumothorax and empyema
Authors: CJ Warburton, PM Calverley
Journal: European Respiratory Journal (1997)

The formation of a gastropleural fistula is an uncommon complication of a number of conditions. The case of a patient with gastropleural fistula, as a complication of gastric lymphoma, is presented. The patient developed a tension pneumothorax and empyema. On cytological examination of the empyematous fluid, the presence of food debris aided diagnosis. The patient died 2 days after a total gastrectomy. The development of this complication in gastric lymphoma appears to have a particularly poor prognosis.
An Underrecognized Subepicardial Reentrant Ventricular Tachycardia Attributable to Left Ventricular Aneurysm in Patients With Normal Coronary Arteriograms
Authors: Feifan Ouyang, Matthias Antz, Florian T. Deger, Dietmar Bänsch, Anselm Schaumann, Sabine Ernst, Karl-Heinz Kuck
Journal: Circulation (2003)

In patients with apparently normal hearts, ventricular tachycardia (VT) may only involve the subepicardial myocardium.Four patients with exercise-induced fast VT with right bundle branch block morphology were investigated. ECG showed a small q wave in leads II, III, and aVF during sinus rhythm (SR) in all 4 patients. Left ventricular angiography showed small inferolateral aneurysms in all patients. Coronary arteriograms were normal in all 4 patients. Six unstable VTs (cycle length, 200 to 305 ms) and 1 stable VT (cycle length 370 ms) were reproducibly induced in the 4 patients. During SR, endocardial mapping was normal in all 4 patients, and epicardial mapping showed fragmented and late potentials in the left inferolateral wall anatomically consistent with the left ventricle aneurysm. During tachycardia, epicardial mapping showed a macroreentrant VT with focal endocardial activation in the patient with stable VT, whereas in 2 patients with unstable VT, a diastolic potential was only recorded and coincided with the late potential in the same area. Epicardial ablation was performed in 3 patients and successfully abolished those VTs. No VT recurred in 2 patients during follow-up of 2 and 9 months. Clinical VT recurred 6 months after the ablation and was successfully ablated in a repeated epicardial ablation in 1 patient. In the remaining patient without epicardial ablation, an implantable cardiac defibrillator was implanted. There were multiple shocks during a follow-up of 31 months.In patients with normal coronary arteriograms and left ventricle aneurysm, exercise-induced VT with right bundle branch block morphology may have a subepicardial arrhythmogenic substrate, which may be amenable to epicardial ablation.
High-frequency oscillatory ventilation is not superior to conventional mechanical ventilation in surfactant-treated rabbits with lung injury
Authors: D. Gommers, A. Hartog, R Schnabel, A De Jaegere, B. Lachmann
Journal: European Respiratory Journal (1999)

The aim of this study was to compare high-frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) with and without surfactant in the treatment of surfactant-deficient rabbits. A previously described saline lung lavage model of lung injury in adult rabbits was used. The efficacy of each therapy was assessed by evaluating gas exchange, lung deflation stability and lung histopathology. Arterial oxygenation did not improve in the CMV group without surfactant but increased rapidly to prelavage values in the other three study groups. During deflation stability, arterial oxygenation decreased to postlavage values in the group that received HFOV alone, but not in both surfactant-treated groups (HFOV and CMV). The HFOV group without surfactant showed more cellular infiltration and epithelial damage compared with both surfactant-treated groups. There was no difference in gas exchange, lung deflation stability and lung injury between HFOV and CMV after surfactant therapy. It is concluded that the use of surfactant therapy in combination with high-frequency oscillatory ventilation is not superior to conventional mechanical ventilation in improving gas exchange, lung deflation stability and in the prevention of lung injury, if lungs are kept expanded. This indicates that achieving and maintaining alveolar expansion (i.e. open lung) is of more importance than the type of ventilator.