tbuckley/cabot-search huggingface dataset:
Glucagon and the circulation.
Authors: A E Farah
Journal: Pharmacological Reviews (1983)

Glucagon is a vasodilator substance that reduces blood pressure via a decreased vascular resistance in the splanchnic and hepatic vasculature. Species differences in the response of various vascular beds to glucagon have been documented. In the kidney, glucagon in relatively large doses increased renal plasma flow, glomerular filtration, and electrolyte excretion. It has been shown that intraarterial injection of glucagon into the renal artery can produce an increase in electrolyte excretion on the side that received an injection with minimal or no changes in glomerular filtration. This indicated a direct tubular effect of this polypeptide. This effect may be related to the increased glomerular filtration observed in poorly controlled diabetics where insulin concentrations are low and glucagon concentrations are high. The tubular effects of glucagon are probably mediated via cAMP and prostaglandin formation in renal tubular cells, especially the ascending limbs of Henle and collecting ducts. Glucagon increases the RNA concentration in glomerular tissue, and this effect is probably independent of cAMP. The latter effect of glucagon has been related to the glomerular enlargement and membrane thickening observed in poorly controlled insulin-dependent diabetics. Starvation natriuresis has been related to increased concentrations of glucagon in blood. The likely mechanism is that glucagon increased the renal excretion of organic acids, possibly by inhibiting the renal tubular reabsorption of these acids. Little is known concerning the effects of glucagon on the cAMP content of vascular smooth muscle. Indirect evidence suggests that such effects may be mediated via the production of cAMP. If this can be established, it would be likely that the glucagon-induced vasodilation is due to a cAMP-dependent phosphorylation of the myosin light chain kinase. This kinase shows reduced sensitivity to the Ca++ calmodulin complex when it is phosphorylated by the cAMP-dependent kinase and thus may produce relaxation of smooth muscle. In cardiac muscle, glucagon produced positive inotropic and chronotropic effects. These effects show species differences and in some species activate only the auricle with minimal effects of ventricular muscle. The effects of glucagon in general resemble those of a beta-adrenergic agent; however, glucagon seems to be nonarrhythmogenic in a variety of cardiac preparations and its effects are not blocked by propranolol. In some of these experimental conditions the chronotropic effects of glucagon play an important role in the antiarrhythmogenic effects, although direct cardiac membrane effects have been postulated. Several factors can modify the
Platelet endothelial aggregation receptor-1: a novel modifier of neoangiogenesis
Authors: Christophe Vandenbriele, Alexandre Kauskot, Ine Vandersmissen, Maarten Criel, Rachel Geenens, Sander Craps, Aernout Luttun, Stefan Janssens, Marc F. Hoylaerts, Peter Verhamme
Journal: Cardiovascular Research (2015)

Platelet endothelial aggregation receptor-1 (PEAR1) is a cell membrane protein, expressed on platelets and endothelial cells (ECs). PEAR1 sustains αIIbβ3 activation in aggregating platelets and attenuates megakaryopoiesis via controlling the degree of Akt phosphorylation. Its role in EC biology is unknown. The aim of this study was to determine the expression of PEAR1 in the human endothelium of various tissues and to investigate its role in ECs in vitro and in angiogenesis, using Pear1−/− mice. PEAR1 is present on the membrane and on filo- and lamellipodia of human cultured ECs, and its expression coincides with CD31 in various tissues. PEAR1 expression is variable in ECs of different origin. Lentiviral knockdown of PEAR1 in cultured ECs doubled EC proliferation and significantly stimulated EC migration, in turn enhancing in vitro tube formation on matrigel through the Akt/PTEN-dependent p21/CDC2 pathway. Even when physiological blood vessel formation was unaffected in Pear1−/− mice, neoangiogenesis in these mice was significantly increased both in a hind limb ischaemia ligation model [4.7-fold increase in capillary density in the ligated limb of Pear1−/− mice compared with ligated limbs in wild-type (WT) mice] and in a skin wound-healing model, resulting in a two-fold faster wound closure in Pear1−/− mice compared with WT littermates. We established an inverse correlation between endothelial PEAR1 expression and vascular assembly both in vitro and in vivo. These findings identify PEAR1 as a novel modifier of neoangiogenesis.
Contact tracing among the classmates of a 15 year old smear negative pulmonary tuberculosis
Authors: Nooshin Baghaie, Soheila Khalilzadeh, Mohammad Reza Boloorsaz, Nazanin Parsanejad
Journal: European Respiratory Journal (2011)

Objectives:  This study aimed to identify the infected or disease cases among contacts of the 15 year old girl with Smear Negative Pulmonary tuberculosis in an school outbreak and establish prophylaxis and treatment needed.   Methods:  52 contacts were screened by a tuberculin skin test and Chest X ray initially, Those children who had either a positive PPD or an abnormal chest X-ray were candidate for a tripled Gastric washing (Smear, Culture, Polymerase chain reaction (PCR)) and a Chest spiral CT scan.   Results:  20 contacts (38%) were considered as an infected due to either positive TST or abnormal Chest X-Ray. 28% had a positive Tuberculin Skin Test. Consequently 3 (5.7%) cases of active TB were identified through our investigations.   Conclusion:  Our study suggest that even children with TB, who may have a negative smear, can transmit infection to others and therefore should be considered infectious until proven otherwise and contact tracing should be considered for contacts of all symptomatic pulmonary tuberculosis children.
PANORAMA 2: A phase II study of panobinostat (LBH589) in combination with bortezomib (BTZ) and dexamethasone (DEX) in patients with relapsed and BTZ-refractory multiple myeloma (MM).
Authors: M. Alsina, S. Lonial, D. M. Weber, S. E. Coutre, B. P. Kang, T. Glynos, G. Warsi, S. M. Snodgrass, P. G. Richardson
Journal: Journal of Clinical Oncology (2010)

TPS308 Background: BTZ, a backbone of novel therapy for patients (pts) with MM, is an effective agent but pts will relapse and ultimately become refractory to BTZ-based therapy as well as other novel agents, thereby constituting a high unmet medical need. Panobinostat (PAN; LBH589) is a potent pan-deacetylase inhibitor (pan-DACi) that targets HDAC6, disrupts aggresome and HSP90 activity, and promotes MM cell death. Combination with BTZ has shown synergistic cytotoxicity in preclinical studies. In a phase Ib MM study, combination of oral PAN with iv BTZ displayed a predictable and manageable safety profile with limited neurotoxicity and clinical efficacy seen with CR + PR + MR in 68% of pts, including 8 of 13 (62%) BTZ-refractory pts. Hence this combination is to be further evaluated in the PANORAMA program (PANobinostat ORAl in Multiple myelomA) Phase III (PANORAMA 1) and Phase II (PANORAMA 2) studies. PANORAMA 2is a U.S.-based, multicenter, single-arm study to evaluate the efficacy of PAN + BTZ + DEX in pts with relapsed and BTZ- refractory MM to assess if the combination with PAN can resensitize pts to BTZ+DEX. Methods: Adult pts with relapsed BTZ- refractory MM (≥2 prior lines of therapy, including an IMiD [thalidomide/lenalidomide], who had progressed on/within 60 days [D] of last BTZ-based therapy) are eligible. Pts receive maximum 8 21-D cycles of PAN (po 20 mg D1, 3, 5, 8, 10, 12) + BTZ (iv 1.3 mg/m2 D1, 4, 8, 11) + DEX (po 20 mg D1, 2, 4, 5, 8, 9, 11, 12). This provides a 1-wk treatment break to maximize tolerability and therapy duration. Per Simon's 2-stage design (H1: ORR >10% vs H0: ORR ≤10%, powered for ORR=25%), Stage 1 will enroll 24 pts. If PR or better in ≥4 pts is seen, 23 additional pts will be enrolled to stage 2. Study endpoint will be met upon ≥8 responses total. Treatment is continued until PD, unacceptable toxicity, or consent withdrawal. Pt follow-up is for 28 D post last dose for safety and up to 2 years for tumor assessment and survival. Primary endpoint is ORR (PR or better); secondary endpoints include MR rate, time to response, DoR, PFS, TTP, OS, and safety, including PN graded by FACT GOG/NTX. Exploratory endpoints include VGPR rate and biomarker studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Bristol-Myers Squibb, Celgene, Facet Biotech, Millennium, Novartis Novartis Novartis Bristol-Myers Squibb, Celgene, Facet Biotech, Gloucester Pharmaceuticals, Millennium, Novartis
Randomized study on the effect of zoledronic acid treatment for prostate cancer with bone metastasis during initial combined androgen blockade.
Authors: Satoru Ueno, Atsushi Mizokami, Mikio Namiki, Takashi Fukagai, Naohiro Fujimoto, Hitoshi Ooka, Yukihiro Kondo, Gaku Arai, Hisamitsu Ide, Kazuyoshi Kataoka, Kohei Kawaguchi, Masayoshi Shimamura, Matsuo Orito, Takeyuki Ishida, Daisuke Ikeda
Journal: Journal of Clinical Oncology (2012)

48 Background: Zoledronic acid (ZA) eventually reduces risk of skeletal morbidity carries beneficial effect on bone pain. Moreover, ZA eventually extends a period to bone pain and the SRE onset after CRPC (castration-resistant prostate cancer) and improves the QOL of the patients. ZA, therefore, has become a standard supportive therapy for CRPC with bone metastasis. However, it remains unclear when the physicians should start ZA treatment for prostate cancer (PCa) patients with bone metastasis. In the present study, we investigated whether we could extend a period before androgen sensitive PCa with bone metastasis becoming CRPC by ZA treatment. Methods: The patients were randomly classified in two groups (combined androgen blockade (CAB) alone group and CAB + ZA treatment group) based on Gleason score (less than 7 or more) EOD score (less than 2 or more). Four mg ZA treatment was conducted every 4 weeks. We evaluated serum PSA value, bone-related markers, and SRE. The first end point was a period before androgen sensitive PCa with bone metastasis becoming CRPC. Results: Untreated 59 PCa patients with bone metastasis were enrolled by 2011 from 2006. Thirty patients were classified in the CAB alone group and 29 patients in the CAB + ZA group. There were no significant difference in age (72,5 and 71.7 yo, respectively), PSA (381.3 ng/ml and 399.0 ng/ml, respectively), Gleason score, and EOD score between CAB alone group and CAB + ZA group. Although there was no significant difference in PSA-progression free survival (PFS) (p=0.14), tendency that CAB + ZA shows better PFS than CAB alone group was observed (time to 50% PFS was extended 9.4 months than CAB alone group). Moreover, the sub analysis using the patients with more than Gleason score 7 or with more than EOD score 1, CAB +ZA group showed better PFS (p=0.074 in Gleason score and p=0.028 in EOD score. Conclusions: This result indicates that CAB with ZA from initial treatment can extend a period before PCa, especially high advanced PCa recurring.
Efficacy of aclidinium bromide in patients with stable COPD: Pooled analysis of phase III data by GOLD 2013 criteria
Authors: Mike Thomas, David Price, Rosa Segarra, Esther Garcia Gil
Journal: European Respiratory Journal (2014)

Background   GOLD 2013 guidelines classify patients with COPD in terms of risk and symptoms (A: low risk, less symptoms; B: low risk, more symptoms; C: high risk, less symptoms and D: high risk, more symptoms). Long-acting muscarinic antagonists such as aclidinium are now recommended as first-choice option for Group B–D patients and as an alternative choice for Group A patients.   Aim   To assess the efficacy of aclidinium 400 µg twice daily (BID) in patients with COPD according to GOLD 2013 criteria.   Methods   Data were pooled from the placebo and aclidinium 400 µg BID arms of three, 6-month, placebo-controlled studies evaluating aclidinium mono- or combination-therapy in patients with moderate-to-severe COPD, stratified to GOLD group using SGRQ total score (surrogate for CAT).   Results   In total, 1787 patients were included (mean±SD: age 63.3±8.4 years, 63.0% male, 54.25±13.13 % predicted). At baseline, mean FEV 1  ranged from 1.103 L (Group C) to 1.695 L (Group A); 7.9% of patients were Group A, 48.4% Group B, 3.1% Group C and 41.4% Group D. At Week 24, aclidinium was associated with improved trough and peak FEV 1  in all GOLD groups compared with placebo (see Table). Numerically the largest differences in trough FEV 1  between aclidinium and placebo were in Group A.   Conclusions   Aclidinium improved lung function in all patients regardless of GOLD group; the numerically largest improvements were in Group A.
Effect of cytostatic agents on the number of alveolar phagocytes and the efficacy of ceftriaxone in an experimental murine lung infection
Authors: W Calame, H Mattie
Journal: European Respiratory Journal (1991)

Mice made monocytopenic and granulocytopenic by cyclophosphamide or monocytopenic by etoposide were infected by exposure to an aerosol containing Klebsiella pneumoniae. Eighteen hours later ceftriaxone was administered and three hours after that the experiment was ended. At the time of infection and at 18 and 21 h the numbers of alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid were significantly lower in the cyclophosphamide-pretreated animals than in the controls. Furthermore, outgrowth of K. pneumoniae in the lungs was significantly stronger in cyclophosphamide-pretreated mice and a fourfold higher dose of ceftriaxone was needed to obtain the same antibacterial effect as in the controls. In the etoposide-pretreated mice the number of alveolar macrophages in BAL was not significantly lower than that in the controls, but the number of granulocytes was. Compared with the controls, there was no significant difference in the number of K. pneumoniae in the lungs, and the efficacy of ceftriaxone did not differ either.
Prospective Study of Coffee Consumption and the Risk of Cancer2
Authors: Abraham Nomura, Lance K. Heilbrun, Grant N. Stemmermann
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Prospective Study of Coffee Consumption and the Risk of Cancer Get access Abraham Nomura, Abraham Nomura Search for other works by this author on: Oxford Academic PubMed Google Scholar Lance K. Heilbrun, Lance K. Heilbrun Search for other works by this author on: Oxford Academic PubMed Google Scholar Grant N. Stemmermann Grant N. Stemmermann Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 4, April 1986, Pages 587–590, https://doi.org/10.1093/jnci/76.4.587 Published: 01 April 1986 Article history Received: 14 March 1985 Revision received: 16 October 1985 Accepted: 02 December 1985 Published: 01 April 1986
Comparative genomic and genetic analysis of glioblastoma-derived brain tumor-initiating cells and their parent tumors
Authors: Brad Davis, Yaoqing Shen, Candice C. Poon, H. Artee Luchman, Owen D. Stechishin, Carly S. Pontifex, Wei Wu, John J. Kelly, Michael D. Blough
Journal: Neuro-Oncology (2015)

BackgroundGlioblastoma (GBM) is a fatal cancer that has eluded major therapeutic advances. Failure to make progress may reflect the absence of a human GBM model that could be used to test compounds for anti-GBM activity. In this respect, the development of brain tumor-initiating cell (BTIC) cultures is a step forward because BTICs appear to capture the molecular diversity of GBM better than traditional glioma cell lines. Here, we perform a comparative genomic and genetic analysis of BTICs and their parent tumors as preliminary evaluation of the BTIC model.
Comparison of efficacy of grippe vaccination in asthma and COPD patients
Authors: Goran Andonovski, Zoran Stojanovski
Journal: European Respiratory Journal (2011)

Objective:  To compare the efficacy of the seasonal grippe vaccination in asthma and COPD patients.   Material and methods:  We evaluate the number of exacerbations and number of hospitalisations in 48 subjects with stage 2 and 3 (moderate/severe) COPD and 45 subjects with mild persistent and moderate persistent Asthma in 6 months period All of them received grippe vaccination before winter. An equal number of COPD and asthma subjects were evaluated like controls. They were not immunized against seasonal influenza. The both groups were matched by sex and age, and receive steroid inhalers (asthmatics), and salbutamol (COPDs) regularly.   Results:  In the first group (immunized subjects) we found 12 (25%) exacerbations and 2 (4,2%) hospitalizations (asthma subjects) and 19 (44,2%) exacerbations and 3 (7,0%) hospitalisations (COPD subjects). Very similar number of exacerbations or hospitalizations we found in non immunized group. But in comparison with previous year (first group) when asthma (48) and COPD (45) subjects didn9t received grippe vaccination the number of hospitalisations were significantly higher ( P     Conclusion:  Our results suggest that grippe vaccination may play role in number of hospitalisations in both. (Asthma and COPD subjects)
Herpes simplex pneumonia in a young immunocompetent man
Authors: E Martinez, A de Diego, A Paradis, M Perpina, M Hernandez
Journal: European Respiratory Journal (1994)

We report the case of a 33 year old man with herpetic bronchitis and bilateral pneumonitis. He presented without mucocutaneous lesions, and his cellular and humoral immunity were not compromised. Diagnosis was established on histological and cytological findings and confirmed by serology. Acyclovir treatment led to a favourable outcome.
Mechanisms of Tumor Homograft Rejection. II. Studies on the Mechanism of Rejection of Sarcoma I Ascites Tumor in the C57BL/Ks Mouse&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Beulah Holmes, Russell S. Weiser
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Mechanisms of Tumor Homograft Rejection. II. Studies on the Mechanism of Rejection of Sarcoma I Ascites Tumor in the C57BL/Ks Mouse Get access Beulah Holmes, Beulah Holmes Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar Russell S. Weiser Russell S. Weiser Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 36, Issue 5, May 1966, Pages 975–983, https://doi.org/10.1093/jnci/36.5.975 Published: 01 May 1966 Article history Received: 08 November 1965 Published: 01 May 1966
Nonalcoholic Fatty Liver Disease
Authors: Mary E. Rinella
Journal: JAMA (2015)

Nonalcoholic fatty liver disease and its subtype nonalcoholic steatohepatitis affect approximately 30% and 5%, respectively, of the US population. In patients with nonalcoholic steatohepatitis, half of deaths are due to cardiovascular disease and malignancy, yet awareness of this remains low. Cirrhosis, the third leading cause of death in patients with nonalcoholic fatty liver disease, is predicted to become the most common indication for liver transplantation.To illustrate how to identify patients with nonalcoholic fatty liver disease at greatest risk of nonalcoholic steatohepatitis and cirrhosis; to discuss the role and limitations of current diagnostics and liver biopsy to diagnose nonalcoholic steatohepatitis; and to provide an outline for the management of patients across the spectrum of nonalcoholic fatty liver disease.PubMed was queried for published articles through February 28, 2015, using the search terms NAFLD and cirrhosis, mortality, biomarkers, and treatment. A total of 88 references were selected, including 16 randomized clinical trials, 44 cohort or case-control studies, 6 population-based studies, and 7 meta-analyses.Sixty-six percent of patients older than 50 years with diabetes or obesity are thought to have nonalcoholic steatohepatitis with advanced fibrosis. Even though the ability to identify the nonalcoholic steatohepatitis subtype within those with nonalcoholic fatty liver disease still requires liver biopsy, biomarkers to detect advanced fibrosis are increasingly reliable. Lifestyle modification is the foundation of treatment for patients with nonalcoholic steatosis. Available treatments with proven benefit include vitamin E, pioglitazone, and obeticholic acid; however, the effect size is modest (<50%) and none is approved by the US Food and Drug Administration. The association between nonalcoholic steatohepatitis and cardiovascular disease is clear, though causality remains to be proven in well-controlled prospective studies. The incidence of nonalcoholic fatty liver disease-related hepatocellular carcinoma is increasing and up to 50% of cases may occur in the absence of cirrhosis.Between 75 million and 100 million individuals in the United States are estimated to have nonalcoholic fatty liver disease and its potential morbidity extends beyond the liver. It is important that primary care physicians, endocrinologists, and other specialists be aware of the scope and long-term effects of the disease. Early identification of patients with nonalcoholic steatohepatitis may help improve patient outcomes through treatment intervention, including transplantation for those with decompensated cirrhosis.
Differences in genetic background of atopic and non-atopic asthma in children
Authors: Vojko Berce, Carina Pinto Kozmus, Uros Potocnik
Journal: European Respiratory Journal (2012)

Background.  Childhood asthma has been divided into phenotypes, which differ in the age of presentation, triggers, lung function and natural history. Despite the enormous increase in the knowledge about asthma genetics, there are very few data regarding the differences in genetic background of asthma phenotypes.   Aims and objectives.  To find out whether the genetic background of atopic and non-atopic asthma differs, we analyzed the association of genetic polymorphisms already associated with asthma or inflammatory diseases with different asthma phenotypes and quantitative traits.   Methods.  We analyzed a case-control cohort composed of 189 Slovenian children aged between 5 and 18 years with mild or moderate persistent atopic asthma, 99 with non-atopic asthma and 273 controls. We measured numerous clinical and laboratory parameters and carried out genotyping for polymorphisms CCR5-delta32, IL4RA Q551R, IL4 C-33T, NOD2 R702W, CTLA4 CT60, MUC7 – VNTR, TNF C-1031T, TGFB1 C-509T, SLC22A4 C1672T, CD14 C-159T and IL23R rs7517847.   Results.  In non-atopic asthmatics the frequency of CCR5-delta32 allele was 2.6%, which is significantly less than 9.0% in the control group (p=0.03) and the frequency of IL4RA Arg551 allele was 7.7%, which is also significantly less than 19.9% in the control group (p   Conclusions.  Our findings point to differences in the pathogenesis of different asthma phenotypes and contribute to understanding of asthma as a complex and heterogeneous disease on the genetic level too.
Measles resurgence in France in 2008, a preliminary report
Authors: I Parent du Châtelet, D Floret, D Antona, D Lévy-Bruhl
Journal: Eurosurveillance (2009)

Since the beginning of 2008, France is experiencing a resurgence of measles. It started in a religious traditionalist group with low coverage and secondarily spread to the general population. This situation is the consequence of the insufficient vaccine coverage (less than 90 % at 24 months of age) which had led to the accumulation of susceptibles over the last years. More than 550 cases have been notified in 2008, the vast majority being unvaccinated. One measles-related death has occurred early 2009. Efforts to enhance communication to the general public and the health professionals on measles vaccination and control measures around cases are ongoing.