tbuckley/cabot-search huggingface dataset:
Evidence Favoring the Use of an α <sub>2</sub> -Selective Vasopressor Agent for Cardiopulmonary Resuscitation
Authors: Tommaso Pellis, Max Harry Weil, Wanchun Tang, Shijie Sun, Jing Xie, Lei Song, Paul Checchia
Journal: Circulation (2003)

Both alpha1- and beta-adrenergic agonists increase the severity of global myocardial ischemic injury. We hypothesized that combined beta- and alpha1-adrenergic blockade would improve initial resuscitation and postresuscitation myocardial and neurological functions. We further hypothesized that the resulting alpha2-actions of relatively brief duration would favor improved functions compared with the more prolonged effect of nonadrenergic vasopressin.Three groups of 5 male domestic pigs weighing 37+/-3 kg were investigated. Ventricular fibrillation was untreated for 7 minutes before the start of precordial compression, mechanical ventilation, and attempted defibrillation. Animals were randomized to receive central venous injections of equipressor doses of (1) epinephrine, (2) epinephrine in which both alpha1- and beta-adrenergic effects were blocked by previous administration of prazosin and propranolol, and (3) vasopressin during CPR. All but 1 animal were successfully resuscitated. After injection of epinephrine, significantly better cardiac output and fractional area change, together with lesser increases in troponin I, were observed after alpha1- and beta-adrenergic blockade. Postresuscitation neurological function was also improved after alpha1- and beta-block in comparison with unblocked epinephrine and after vasopressin.Equipressor doses of epinephrine, epinephrine after alpha1- and beta-adrenergic blockade, and vasopressin were equally effective in restoring spontaneous circulation after prolonged ventricular fibrillation. However, combined alpha1- and beta-adrenergic blockade, which represented a predominantly selective alpha2-vasopressor effect, resulted in improved postresuscitation cardiac and neurological recovery.
Cardiac hypertrophy and histone deacetylase–dependent transcriptional repression mediated by the atypical homeodomain protein Hop
Authors: Hyun Kook, John J. Lepore, Aaron D. Gitler, Min Min Lu, Wendy Wing-Man Yung, Joel Mackay, Rong Zhou, Victor Ferrari, Peter Gruber, Jonathan A. Epstein
Journal: Journal of Clinical Investigation (2003)

Activation of multiple pathways is associated with cardiac hypertrophy and heart failure. Repression of antihypertrophic pathways has rarely been demonstrated to cause cardiac hypertrophy in vivo. Hop is an unusual homeodomain protein that is expressed by embryonic and postnatal cardiac myocytes. Unlike other homeodomain proteins, Hop does not bind DNA. Rather, it modulates cardiac growth and proliferation by inhibiting the transcriptional activity of serum response factor (SRF) in cardiomyocytes. Here we show that Hop can inhibit SRF-dependent transcriptional activation by recruiting histone deacetylase (HDAC) activity and can form a complex that includes HDAC2. Transgenic mice that overexpress Hop develop severe cardiac hypertrophy, cardiac fibrosis, and premature death. A mutant form of Hop, which does not recruit HDAC activity, does not induce hypertrophy. Treatment of Hop transgenic mice with trichostatin A, an HDAC inhibitor, prevents hypertrophy. In addition, trichostatin A also attenuates hypertrophy induced by infusion of isoproterenol. Thus, chromatin remodeling and repression of otherwise active transcriptional processes can result in hypertrophy and heart failure, and this process can be blocked with chemical HDAC inhibitors.
Efficacy of intra-articular bevacizumab for relapsing diffuse-type giant cell tumour
Authors: M J Nissen, A Boucher, L Brulhart, J Menetrey, C Gabay
Journal: Annals of the Rheumatic Diseases (2014)

Diffuse-type giant cell tumours (GCT), also known as pigmented villonodular synovitis, are characterised by synovial hypertrophy that affects one or several joints, bursas or tendon sheaths, especially in young adults.1 GCT are generally treated by surgical synovectomy.1 ,2 However, the recurrence rate is high, with figures of up to 55%.3 Adjuvant therapies exist, such as external beam radiotherapy (EBM) or intra-articular injection of radiopharmaceuticals (eg, yttrium-90).4–⇓6 Nevertheless, outcomes remain suboptimal and new management options are required. We describe herein the use of bevacizumab, a humanised monoclonal antivascular endothelial growth factor (VEGF) antibody, as an alternative therapy in a case of severe and refractory diffuse-type GCT.

A 24-year-old man without prior past medical history consulted for painful knee swelling. Arthroscopy with biopsy was performed and the …
Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial
Authors: Edo Vellenga, Wim L. J. van Putten, Mars B. van 't Veer, Josée M. Zijlstra, Willem E. Fibbe, Marinus H. J. van Oers, Leo F. Verdonck, Pierre W. Wijermans, Gustaaf W. van Imhoff, Pieternella J. Lugtenburg, Peter C. Huijgens
Journal: Blood (2007)
Multimodal therapy with intravenous biweekly leucovorin, 5-fluorouracil and irinotecan combined with hepatic arterial infusion pirarubicin in non-resectable hepatic metastases from colorectal cancer (a European Association for Research in Oncology trial)
Authors: L. Zelek, R. Bugat, D. Cherqui, G. Ganem, P. Valleur, R. Guimbaud, O. Dupuis, T. Aziza, P.L. Fagniez, J. Auroux, H. Kobeiter, C. Tayar, A.C. Braud, E. Haddad, A. Piolot, M. Buyse, P. Piedbois
Journal: Annals of Oncology (2003)
Pulmonary deposition of a nebulised aerosol during mechanical ventilation.
Authors: S H Thomas, M J O'Doherty, H M Fidler, C J Page, D F Treacher, T O Nunan
Journal: Thorax (1993)

BACKGROUND: There is increasing use of therapeutic aerosols in patients undergoing mechanical ventilation. Few studies have measured aerosol delivery to the lungs under these conditions with adequate experimental methods. Hence this study was performed to measure pulmonary aerosol deposition and to determine the reproducibility of the method of measurement during mechanical ventilation. METHODS: Nine male patients were studied during mechanical ventilation after open heart surgery and two experiments were performed in each to determine the reproducibility of the method. A solution of technetium-99m labelled human serum albumin (99mTc HSA (50 micrograms); activity in experiment 1, 74 MBq; in experiment 2, 185 MBq) in 3 ml saline was administered with a Siemens Servo 945 nebuliser system (high setting) and a System 22 Acorn nebuliser unit. Pulmonary deposition was quantified by means of a gamma camera and corrections derived from lung phantom studies. RESULTS: Pulmonary aerosol deposition was completed in 22 (SD 4) minutes. Total pulmonary deposition (% nebuliser dose (SD)) was 2.2 (0.8)% with 1.5% and 0.7% depositing in the right and left lungs respectively; 0.9% of the nebuliser activity was detected in the endotracheal tube or trachea and 51% was retained within the nebuliser unit. Considerable variability between subjects was found for total deposition (coefficient of variation (CV) 46%), but within subject reproducibility was good (CV 15%). CONCLUSIONS: Administration of aerosol in this way is inefficient and further research is needed to find more effective alternatives in patients who require mechanical respiratory support. This method of measurement seems suitable for the assessment of new methods of aerosol delivery in these patients.
IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland
Authors: Pasquale Sansone, Gianluca Storci, Simona Tavolari, Tiziana Guarnieri, Catia Giovannini, Mario Taffurelli, Claudio Ceccarelli, Donatella Santini, Paola Paterini, Kenneth B. Marcu, Pasquale Chieco, Massimiliano Bonafè
Journal: Journal of Clinical Investigation (2007)

High serum levels of IL-6 correlate with poor outcome in breast cancer patients. However, no data are available on the relationship between IL-6 and mammary stem/progenitor cells, which may fuel the genesis of breast cancer in vivo. Herein, we address this issue in the MCF-7 breast cancer cell line and in primary human mammospheres (MS), multicellular structures enriched in stem/progenitor cells of the mammary gland. MS from node invasive breast carcinoma tissues expressed IL-6 mRNA at higher levels than did MS from matched non-neoplastic mammary glands. In addition, IL-6 mRNA was detected only in basal-like breast carcinoma tissues, an aggressive breast carcinoma variant showing stem cell features. IL-6 treatment triggered Notch-3–dependent upregulation of the Notch ligand Jagged-1 and promotion of MS and MCF-7–derived spheroid growth. Moreover, IL-6 induced Notch-3–dependent upregulation of the carbonic anhydrase IX gene and promoted a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS. Finally, autocrine IL-6 signaling relied upon Notch-3 activity to sustain the aggressive features of MCF-7–derived hypoxia-selected cells. In conclusion, these data support the hypothesis that IL-6 induces malignant features in Notch-3–expressing stem/progenitor cells from human ductal breast carcinoma and normal mammary gland.
A PURE STRAIN OF CARTILAGE CELLS IN VITRO
Authors: Albert Fischer
Journal: The Journal of Experimental Medicine (1922)

1. A strain of cartilage cells, obtained from the pars cartilago sclerae of the eye of chick embryos, has been cultivated for more than 3 months in vitro. 2. The initial growth of the cartilage was possible only on the free surface of the coagulum. 3. The hyaline substance disappeared during cultivation in vitro. The succeeding stages of a transformation from small, lymphocyte-like cells into large, spindle-shaped cells were observed. The cartilage cells were spindle-shaped and grew in close contact, forming thin membranes. In surface-grown cartilage cells, the nucleus, usually containing one large nucleolus, stained less deeply than the cytoplasm. 4. The rate of growth of cartilage was slower than that of fibroblasts and epithelium. After cultivation on the surface of the coagulum, the cartilage cells could multiply even when embedded in the coagulum. But their growth was less extensive and uniform.
HDAC6 Inhibition Restores Ciliary Expression and Decreases Tumor Growth
Authors: Sergio A. Gradilone, Brynn N. Radtke, Pamela S. Bogert, Bing Q. Huang, Gabriella B. Gajdos, Nicholas F. LaRusso
Journal: Cancer Research (2013)

Abstract Primary cilia are multisensory organelles recently found to be absent in some tumor cells, but the mechanisms of deciliation and the role of cilia in tumor biology remain unclear. Cholangiocytes, the epithelial cells lining the biliary tree, normally express primary cilia and their interaction with bile components regulates multiple processes, including proliferation and transport. Using cholangiocarcinoma as a model, we found that primary cilia are reduced in cholangiocarcinoma by a mechanism involving histone deacetylase 6 (HDAC6). The experimental deciliation of normal cholangiocyte cells increased the proliferation rate and induced anchorage-independent growth. Furthermore, deciliation induced the activation of mitogen-activated protein kinase and Hedgehog signaling, two important pathways involved in cholangiocarcinoma development. We found that HDAC6 is overexpressed in cholangiocarcinoma and overexpression of HDAC6 in normal cholangiocytes induced deciliation and increased both proliferation and anchorage-independent growth. To evaluate the effect of cilia restoration on tumor cells, we targeted HDAC6 by short hairpin RNA (shRNA) or by the pharmacologic inhibitor, tubastatin-A. Both approaches restored the expression of primary cilia in cholangiocarcinoma cell lines and decreased cell proliferation and anchorage-independent growth. The effects of tubastatin-A were abolished when cholangiocarcinoma cells were rendered unable to regenerate cilia by stable transfection of IFT88-shRNA. Finally, inhibition of HDAC6 by tubastatin-A also induced a significant decrease in tumor growth in a cholangiocarcinoma animal model. Our data support a key role for primary cilia in malignant transformation, provide a plausible mechanism for their involvement, and suggest that restoration of primary cilia in tumor cells by HDAC6 targeting may be a potential therapeutic approach for cholangiocarcinoma. Cancer Res; 73(7); 2259–70. ©2013 AACR.
Frequency of Gestational Diabetes Mellitus at Collaborating Centers Based on IADPSG Consensus Panel–Recommended Criteria
Authors: David A. Sacks, David R. Hadden, Michael Maresh, Chaicharn Deerochanawong, Alan R. Dyer, Boyd E. Metzger, Lynn P. Lowe, Donald R. Coustan, Moshe Hod, Jeremy J.N. Oats, Bengt Persson, Elisabeth R. Trimble
Journal: Diabetes Care (2012)

OBJECTIVE To report frequencies of gestational diabetes mellitus (GDM) among the 15 centers that participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study using the new International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. RESEARCH DESIGN AND METHODS All participants underwent a 75-g oral glucose tolerance test between 24 and 32 weeks’ gestation. GDM was retrospectively classified using the IADPSG criteria (one or more fasting, 1-h, or 2-h plasma glucose concentrations equal to or greater than threshold values of 5.1, 10.0, or 8.5 mmol/L, respectively). RESULTS Overall frequency of GDM was 17.8% (range 9.3–25.5%). There was substantial center-to-center variation in which glucose measures met diagnostic thresholds. CONCLUSIONS Although the new diagnostic criteria for GDM apply globally, center-to-center differences occur in GDM frequency and relative diagnostic importance of fasting, 1-h, and 2-h glucose levels. This may impact strategies used for the diagnosis of GDM.
New insights into intestinal secretion
Authors: Jörg D Schulzke, Britta Siegmund, Dorothee Günzel
Journal: Gut (2013)

Apart from malabsorption and intestinal barrier dysfunction (via a ‘leak-flux’ mechanism), diarrhoea may reflect active ion secretion in the small intestine and/or colon. In recent years, our understanding about intestinal secretory mechanisms has increased enormously. Important new findings are (1) chloride, bicarbonate and potassium may be secreted simultaneously, but via independent transport processes and (2) movement of a specific ion across cell membranes may occur via several types of channels selective for that ion, but differing in their molecular structure and intrinsic biophysical properties. Additionally, Linley and coworkers now present evidence that (3) specific types of chloride and potassium channels involved in chloride and potassium secretion are differentially expressed in the apical membrane of enterocytes and goblet cells along the surface cell-crypt cell axis. Thus, we are now in a position to reconsider the ancient concept of exclusively secretory crypt cells and absorptive surface cells.1

In general, underlying active intestinal ion secretion is Na+/K+-ATPase-dependent primary transport, which results in low intracellular sodium and high intracellular potassium concentrations. The sodium gradient across the basolateral membrane facilitates basolateral chloride or bicarbonate uptake via sodium-coupled cotransport (secondary active transport), as a result of which these anions accumulate intracellularly above their electrochemical equilibrium. As a result of this gradient across the apical membrane, they are subsequently …
Phase I and Pharmacokinetic Study of 7-Hydroxystaurosporine and Carboplatin in Advanced Solid Tumors
Authors: Martin J. Edelman, Kenneth S. Bauer, Suhlan Wu, Ruth Smith, Sonia Bisacia, Janet Dancey
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Based on preclinical data showing synergy between 7-hydroxystaurosporine (UCN-01) and platinum agents, a phase I trial of carboplatin with UCN-01 administered as a 3 h infusion in patients with advanced solid tumors was done. The primary goals of this trial were to evaluate the tolerability of this combination and the pharmacokinetics of UCN-01 when administered over 3 h and to compare the tolerability and pharmacokinetics with previously described schedules. Patients and Methods: Patients with advanced solid tumors, good performance status, normal organ function, and no potentially curative therapy were eligible for the trial. Carboplatin was escalated from an area under the curve (AUC) of 3 to an AUC of 5. UCN-01 was escalated from 50 to 90 mg/m2. Results: Twenty-three patients with advanced solid tumors (20 with prior platinum treatment) received a total of 60 cycles of therapy. Full doses of both agents (carboplatin AUC 5, UCN-01 90 mg/m2 in cycle 1, 45 mg/m2 in subsequent cycles) could be administered. The major toxicity noted was hypotension, which could be abrogated with the use of saline prehydration and posthydration. No responses were seen; however, seven patients were able to receive more than two courses of therapy. Of note, two of three patients with refractory, progressive small cell lung cancer were able to receive six cycles of therapy without evidence of progression. One patient experienced resolution of paraneoplastic syndrome of inappropriate antidiuretic hormone. The pharmacokinetic variables Cmax and t1/2 of the 3 h infusion were essentially identical to those previously observed when UCN-01 was administered over 72 h. The average t1/2 for cycle 1 was 506 ± 301 h, and the mean Cmax for all dose levels was &amp;gt;30 μmol/L. The mean AUC over the dosing interval for each dose level ranged from ∼6,000 to 9,000 μmol/L h. Thus, the AUC of UCN-01 after the 3 h infusion was lower than was observed after a 72 h infusion. Conclusion: The regimen of carboplatin and UCN-01 (administered as a 3 h infusion) was well tolerated. Further development of this combination, particularly in small cell lung cancer, is warranted.
Association of Increased Upper Trunk and Decreased Leg Fat With 2-h Glucose in Control and HIV-Infected Persons
Authors: Lisa A. Kosmiski, Rebecca Scherzer, Steven B. Heymsfield, David Rimland, Michael S. Simberkoff, Stephen Sidney, Michael G. Shlipak, Peter Bacchetti, Mary L. Biggs, Carl Grunfeld
Journal: Diabetes Care (2011)

Changes in body fat distribution and abnormal glucose metabolism are common in HIV-infected patients. We hypothesized that HIV-infected participants would have a higher prevalence of impaired glucose tolerance (IGT) compared with control subjects.A total of 491 HIV-infected and 187 control participants from the second examination of the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) underwent glucose tolerance testing (GTT). Multivariable regression was used to identify factors associated with GTT parameters.The prevalence of impaired fasting glucose (IFG) (>110 mg/dL) was similar in HIV-infected and control participants (21 vs. 25%, P = 0.23). In those without IFG, the prevalence of IGT was slightly higher in HIV-infected participants compared with control subjects (13.1 vs. 8.2%, P = 0.14) and in HIV+ participants with lipoatrophy versus without (18.1 vs. 11.5%, P = 0.084). Diabetes detected by GTT was rare (HIV subjects 1.3% and control subjects 0%, P = 0.65). Mean 2-h glucose levels were 7.6 mg/dL higher in the HIV-infected participants (P = 0.012). Increased upper trunk subcutaneous adipose tissue (SAT) and decreased leg SAT were associated with 2-h glucose and IGT in both HIV-infected and control participants. Adjusting for adipose tissue reduced the estimated effects of HIV. Exercise, alcohol use, and current tenofovir use were associated with lower 2-h glucose levels in HIV-infected participants.In HIV infection, increased upper trunk SAT and decreased leg SAT are associated with higher 2-h glucose. These body fat characteristics may identify HIV-infected patients with normal fasting glucose but nonetheless at increased risk for diabetes.
Early and late effects of exercise and athletic training on neural mechanisms controlling heart rate
Authors: R. Furlan, S. Piazza, S. Dell'Orto, E. Gentile, S. Cerutti, M. Pagani, A. Malliani
Journal: Cardiovascular Research (1993)

Objective: This study addresses the long term and short term effects of heavy dynamic exercise on neural control of heart rate. Methods: A group of healthy controls was compared with (1) a group of trained athletes during a period of yearly rest (detrained) and (2) a group of trained athletes at the peak of their training routine. Additionally, a group of 10 controls was studied 1, 24, and 48 h after a single bout of maximal dynamic exercise. Spectral analysis of RR interval variability provided markers of sympathetic (low frequency, LF, 0.10 Hz) and vagal (high frequency, HF, 0.25 Hz) modulation of the sinoatrial node. Results: (1) In detrained athletes resting bradycardia was accompanied by a predominant HF rhythmic component suggestive of a prevailing vagal tone. (2) Trained athletes showed a resting bradycardia together with high LF values, thus suggesting a more complex neural interaction modulating heart rate. An additional longitudinal part of the study, performed on a group of detrained athletes who were examined for the second time after resuming training, confirmed the finding of a prevailing LF component in resting conditions. (3) In the 10 control subjects maximal dynamic exercise induced an increase in LF which outlasted the cessation of exercise up to 24 h, suggesting a persistent sympathetic activation. (4) Passive tilt, a manoeuvre which enhances sympathetic drive, produced a greater enhancement of the LF component in trained athletes than in control subjects. Conclusions: The cardiac sympathetic excitation outlasting heavy dynamic exercise may explain the coexistence of training bradycardia with signs of enhanced sympathetic activity in trained champion athletes. Cardiovascular Research 1993;27:482-488
Inherited factors in diffuse bronchiectasis in the adult: a prospective study
Authors: F Verra, E Escudier, J Bignon, MC Pinchon, M Boucherat, JF Bernaudin, H de Cremoux
Journal: European Respiratory Journal (1991)

To evaluate the prevalence of inherited respiratory ciliary structure and underlying mucus abnormalities in the diffuse bronchiectasis syndrome, we investigated 53 subjects comprising 38 patients with diffuse bronchiectasis confirmed by high-resolution thoracic computed tomography, ten with chronic bronchitis and no diffuse bronchiectasis and five healthy nonsmoking control subjects. The clinical history was determined by means of a standardized questionnaire. Axonemal abnormalities of respiratory cilia were evaluated on bronchial or nasal mucosa samples by transmission electron microscopy (structure) and stroboscopic observation (function). Cystic fibrosis (CF) and Young's syndrome were detected by means of the sweat test and semen analysis when male infertility was suspected. Among the 38 patients with diffuse bronchiectasis, a primary ciliary dyskinesia (PCD) was detected in five (13%) with a high proportion (range: 55-100%) of cilia showing axonemal ultrastructural abnormalities always involving the dynein arms. The prevalence of this inherited condition was higher in North African (36%) than in European patients (4%) (p less than 0.01). After exclusion of the five patients with PCD, the patients with diffuse bronchiectasis showed axonemal ultrastructural abnormalities similar to those with chronic bronchitis. The diagnosis of underlying mucus disorders was based on two types of criterion, i.e. for CF, sweat chloride levels greater than 80 mmol.l-1, or the combination of diagnostic criteria proposed by Stern et al. Respectively, five (three Young's syndrome and two CF) and seven (one Young's syndrome and six CF) cases of inherited mucus disorders were suspected. Our results showed that PCD was highly prevalent among the adult North African patients with diffuse bronchiectasis but relatively rare in the Europeans.