tbuckley/cabot-search huggingface dataset:
MicroRNA-155 controls pulmonary artery fibroblast cell signalling and proliferation in a knockout mouse model: A role in pulmonary arterial hypertension
Authors: Neil McGlinchey, Connor Bradley, Charles McSharry, Andrew Peacock, David Welsh
Journal: European Respiratory Journal (2014)

Background  Fibroblast proliferation mediated by p38 mitogen-activated protein kinase (p38MAPK) signalling contributes to adventitial thickening in experimental models of pulmonary arterial hypertension (PAH). MicroRNA-155 (miR-155) over expression can down regulate Smad5, a key signalling molecule in the Bone Morphogenetic Protein type-2 receptor (BMPR2) pathway, thereby potentially mimicking the loss-of-function BMPR2 mutations that can cause PAH.  Aims  We hypothesised that miR-155 down regulation would protect against enhanced hypoxic fibroblast proliferation by altering Smad5 and p38MAPK pathway activity.  Methods  Pulmonary adventitial fibroblasts (PAFs) isolated from miR-155 knockout (miR-155 -/- ) and wild-type (WT) mice were cultured in normoxia and hypoxia at various serum concentrations. Smad5 and p38MAPK expression was detected by Western blotting. Proliferation was assessed by [ 3 H] Thymidine incorporation.  Results  miR -/-  fibroblasts showed less p38 MAPK activity (phosphorylation) in hypoxia (see Fig. 1) and increased Smad5 signalling compared with WT cells.  WT fibroblasts proliferated to a higher degree in hypoxic conditions compared to normoxic controls. This effect was abrogated in the miR-155 -/-  cells.  Conclusion  miR-155 may play a role in the pathogenesis of PAH via its control of key signalling pathways linked to pulmonary vascular remodelling.
Abstract 18596: Regional Assessment of Lower Extremity Tissue Oxygenation in Athletes Using Blood Oxygen Level-Dependent Magnetic Resonance Imaging
Authors: Mitchel R Stacy, Christopher M Caracciolo, Prasanta Pal, Maolin Qiu, Smita Sampath, Albert J Sinusas
Journal: Circulation (2013)

Background: Blood oxygen level-dependent (BOLD) MRI allows for evaluation of hemoglobin oxygenation within skeletal muscle, providing a non-invasive index of microvascular function. This study evaluated differences in relative signal intensity of BOLD MRI among lower extremity muscle groups during transient ischemia and reactive hyperemia in college football athletes, while also comparing strength and functional exercise results. Methods: BOLD MRI was performed on the lower leg of 19 males (19.8 ± 1.0 yrs) with a 3T magnet to evaluate regional changes in signal intensity among individual muscle groups during ischemia and reactive hyperemia induced by proximal cuff occlusion. Athletes were separated by position (larger linemen vs. smaller position players) for comparison purposes. The peak hyperemic value (PHV), or the maximum percent change in BOLD signal intensity from baseline, was assessed for each muscle group. Athletes’ lower body strength and jumping ability were evaluated and compared to BOLD responses. Results: Linemen presented with higher body fat and systolic blood pressure (p&lt;0.05). Athletes did not differ in maximal lower body strength; however, position players had greater vertical and broad jump performance (p&lt;0.0001). In analysis of all athletes, the soleus muscle, a slow twitch muscle generally with high capillary density, exhibited the largest PHV. The PHVs of gastrocnemius muscles for position players were significantly higher than linemen (p=0.03) and were associated with greater jumping performance. No differences were observed in other muscle groups when comparing position players and linemen. Conclusions: BOLD MRI offers a non-invasive technique for quantifying regional differences in lower extremity tissue oxygenation in the evaluation of microvascular function in relation to functional performance. Evaluation of changes in BOLD responses may help to evaluate and optimize exercise training for improved function.
Phase II trial of irinotecan in patients with metastatic colorectal carcinoma.
Authors: H C Pitot, D B Wender, M J O'Connell, G Schroeder, R M Goldberg, J Rubin, J A Mailliard, J A Knost, C Ghosh, R J Kirschling, R Levitt, H E Windschitl
Journal: Journal of Clinical Oncology (1997)

PURPOSE To evaluate the objective tumor response rate and toxicities of patients with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT-11). PATIENTS AND METHODS A total of 121 patients with advanced colorectal carcinoma--90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically naive patients--were enrolled between May 1993 and June 1994. Patients were treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2-week rest. RESULTS Among 90 patients with prior 5-FU chemotherapy, 12 partial responses were observed (response rate, 13.3%; 95% confidence interval [CI], 7.1% to 22.1%). Among 31 chemotherapy-naive patients, eight had partial responses (response rate, 25.8%; 95% CI, 11.9% to 44.6%). The median response duration as measured from time of initial treatment for the two groups was 7.7 months and 7.6 months, respectively. The major adverse reactions were gastrointestinal and hematologic. The incidence of grade 3 or 4 diarrhea was 36.4%, while the overall incidence of grade 3 or 4 leukopenia was 21.5% of patients. Only four of 121 patients (3.3%) developed neutropenic fever (grade 4 neutropenia with &gt; or = grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with prior pelvic radiotherapy (chi2 test P = .04), while the incidence of grade 3 or 4 diarrhea demonstrated no association with previous pelvic irradiation. CONCLUSION According to the study design, CPT-11 showed promising activity in chemotherapy-naive patients with advanced colorectal carcinoma and modest activity in patients with prior 5-FU exposure. The toxicity with this schedule appears manageable with appropriate dose modification for individual patient tolerance and an intensive loperamide regimen for the management of diarrhea. Care should be taken when treating patients with prior pelvic radiotherapy because of the increased risk of neutropenia.
Fluorouracil in colorectal cancer--a tale of two drugs: implications for biochemical modulation.
Authors: A F Sobrero, C Aschele, J R Bertino
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine if fluorouracil (FUra) has different mechanisms of action as a function of the dose schedule used. DESIGN The preclinical and clinical literature relating toxicity and antitumor effects of FUra as a function of its dose schedule, with and without modulating agents, was reviewed. RESULTS The data support the hypothesis that FUra may be considered to be two different drugs, depending on its dose schedule (bolus v continuous infusion [CI]). CONCLUSION These results suggest that additional therapeutic benefit may be obtained from FUra regimens by (1) appropriate schedule-dependent modulation, (2) the sequential or alternating use of cycles of bolus followed by cycles of CI FUra appropriately modulated, or (3) hybrid regimens, ie, those that contain both pulse and CI schedules.
Where does the impact of pulmonary rehabilitation happen
Authors: Latinka Basara Toromanovic, Tajana Jalusic Gluncic
Journal: European Respiratory Journal (2013)

Background. Pulmonary rehabilitation (PR) has proven its benefits with specific impairment in pulmonary disease and the functional difficulties emerging from that impairment. Reduction in functional difficulties reflects in better quality of life, lowered depression and anxiety symptoms more than in improved objective measures of pulmonary function.  Aim. The aim of this study was to assess in which segments does the impact of PR occur and to see weather asthma and COPD patients deffer in size of the impact. We hypothesised that the main impact is sustained in subjective measures of improved health.  Methods. Retrospective data was gathered from 95 outpatients with asthma and COPD who completed comprehensive PR program through 15-20 scheduled visits. Data was gathered from disease specific questionnaires of symptom control (ACT, CAT), pulmonary function tests, 6-min walking test, saturation and psychological variables – depression, anxiety, stress and quality of life.  Results. We found significant difference in asthma and COPD symptom control pre and post treatment (p(ACT,CAT)  Conclusions. The impact of pulmonary rehabilitation mainly consists of improvements in symptom control, FEV1, 6-minute walking test result, quality of life and anxiety, depression and stress levels. It seems that asthma and COPD patients do not differ in the effects of pulmonary rehabilitation program.
Risk factors that determine time to first RSV hospitalization in CARESS: The Canadian registry of palivizumab (2005-2011)
Authors: Ian Mitchell, Bosco Paes, Krista Lanctot, Abby Li
Journal: European Respiratory Journal (2012)

Objective: Evaluate risk factors that determine time to first RSV hospitalization in children at high-risk of RSV infection who received prophylaxis.  Design/Methods: A prospective, observational, registry of infants who received 1 dose of palivizumab during the 2005-2011 RSV seasons across 30 sites. Neonatal and demographic data were collected from the parent/caregiver at enrollment. Data related to respiratory infection events were collected monthly.  Results: 10,452 infants were enrolled; average age 5.5±6.0 months. Infants were typically male (56.4%), Caucasian (71.3%), average gestational age (GA) 32.3±5.6 completed weeks. 7006 (67%) infants received palivizumab for prematurity (35 weeks GA) only, 836 (8 %) had chronic lung disease, 1048 (10%) had congenital heart disease and 1562 (15%) had underlying medical disorders (e.g. CNS disorders, airway anomalies and cystic fibrosis). Hospitalization rates for respiratory and RSV-related illness were 6.4% and 1.6%, respectively. Risk factors that predicted RSV hospitalization included: having siblings (HR=2.16, df=1, p=0.001), >5 people in household (HR=2.02, df=1, p  Conclusions: Time to first RSV hospitalization after the first palivizumab dose are similar to those reported in the literature, with a natural history of RSV. The effect of multiple risk factors pose a cumulative increased risk for RSV hospitalization, similar to the Canadian and European risk scoring models for 33-35 weeks9 GA infants.
Tumor clock protein PER2 as a determinant of survival in patients (pts) receiving oxaliplatin-5-FU-leucovorin as first-line chemotherapy for metastatic colorectal cancer (MCC)
Authors: S. Iacobelli, P. Innominato, M. Piantelli, G. A. Bjarnason, B. Coudert, C. Focan, S. Giacchetti, A. Poncet, C. Garufi, F. Lévi
Journal: Journal of Clinical Oncology (2008)

11032 Background: The molecular circadian clock controls malignant proliferation and drug metabolism, with Period 2 (Per2) playing a central role (Nat Rev Cancer 2003, 3: 350; Ann Rev Pharm Toxicol 2007, 47:593). Per genes are down regulated in human breast, lung, gynecologic and blood malignancies. We investigate for the 1st time PER protein expressions in primary tumor (TUM) and in colonic mucosa (MUC) in MCC pts receiving FOLFOX2 or chronoFLO4 (EORTC 05963) (J Clin Oncol 2006, 24:3562) and correlate their expression to pt and tumor features and to clinical outcome. Methods: 13/25 centers (5 countries) collected paraffin-embedded TUM and MUC. PER1, PER2 and PER3 expression were assessed in two 2-mm carrots from each sample with tissue microarrays (TMA) using C-20, N-19 and Q-16 goat polyclonal primary antibodies (S. Cruz Biotechnology, USA). MUC was positive (+) if ≥1% cells expressed PER. The % labeled tumor cells (> 300 counted by 2 pathologists) were categorized as terciles. Results: 221 samples were retrieved (56% of corresponding pt accrual), with 180 adequate for TMA, representative of the trial population characteristics and outcome. The % TUM cells expressing PER1, PER2 and PER3 were significantly correlated (p<0.001). 21% of the pts shared lowest expression of all 3 PERs in TUM. PER2 was not detected in 26% of TUM vs 17% of MUC (p = 0.007). 19% of the pts with constitutive expression of PER2 in MUC had undetectable PER2 in TUM. No significant correlation was found between TUM PER1 or PER3 and pt outcome. The % tumor cells expressing PER2 predicted for PFS (Log Rank, p= 0.049). Furthermore, median overall survival ranged from 16.3 months (mo) (1st tercile, 0- 10% of PER2+ cells) to 18.1 mo (2nd tercile, 11–66%) and 22.6 mo (3rd tercile, 67–100%) (p = 0.038). Multivariate Cox analyses confirmed PER2 expression in primary tumor as an independent prognostic factor of survival (p= 0.036), jointly with performance status (p<0.001) and number of metastatic sites (p=0.007) Conclusions: Down regulation of core clock gene Per2 in tumors predicted for poor survival in chemo-naive pts with metastatic colorectal cancer. This is the first report of an association between clock gene down regulation and outcome in any cancer. No significant financial relationships to disclose.
Multicenter evaluation of the reproducibility of the proposed antifungal susceptibility testing method for fermentative yeasts of the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST)
Authors: M. Cuenca-Estrella, C.B. Moore, F. Barchiesi, J. Bille, E. Chryssanthou, D.W. Denning, J.P. Donnelly, F. Dromer, B. Dupont, J.H. Rex, M.D. Richardson, B. Sancak, P.E. Verweij, J.L. Rodríguez-Tudela
Journal: Clinical Microbiology and Infection (2003)
Abstract 3429: Amlodipine Improves Endothelial Function and Metabolic Parameters in Patients with Hypertension
Authors: Kwang K Koh, Michael J Quon, Seung H Han, Wook-Jin Chung
Journal: Circulation (2007)

Background : Reciprocal relationships between endothelial dysfunction and insulin resistance imply that improvement in endothelial dysfunction will have beneficial metabolic consequences. We hypothesized that amlodipine therapy will improve endothelial dysfunction and metabolic parameters in hypertensive subjects. Methods : Amlodipine (10 mg daily for 8 weeks) or placebo was given to each 45 patients with mild to moderate hypertension in a randomized, double-blind, placebo-controlled, and paralleled study. Age, sex, and body mass index were matched. Results : Amlodipine therapy significantly reduced systolic and diastolic blood pressure and increased HDL-cholesterol to greater extent than placebo therapy (all P&lt; 0.001). Amlodipine therapy significantly improved flow-mediated dilator response to hyperemia and reduced plasma malondialdehyde levels to greater extent than placebo therapy ( P&lt; 0.001 and P =0.035). Amlodipine therapy significantly increased plasma adiponectin levels ( P =0.009) and decreased plasma leptin and resistin levels ( P&lt; 0.001 and P =0.025, respectively) to greater extent than placebo therapy. Correlations were noted between percent changes in adiponectin levels and percent changes in HDL-cholesterol ( r =0.348, P =0.019) and QUICKI ( r =0.326, P =0.029) following amlodipine therapy. Only changes in HDL-cholesterol (β = 0.469, P = 0.019) and QUICKI (β = 1.786, P = 0.069) were independent predictors of changes in adiponectin levels (multivariate regression analysis). We also observed inverse correlations between percent changes in leptin levels and percent changes in QUICKI ( r = −0.569, P&lt; 0.001) following amlodipine therapy with changes in QUICKI (β = 1.810, P &lt; 0.001) as an independent predictor of changes in leptin levels. Conclusions : Amlodipine therapy improves blood pressure, endothelial function, and metabolic parameters in patients with hypertension.
Diagnosing infection in febrile granulocytopenic patients with indium-111-labeled human immunoglobulin G.
Authors: W J Oyen, R A Claessens, J M Raemaekers, B E de Pauw, J W van der Meer, F H Corstens
Journal: Journal of Clinical Oncology (1992)

PURPOSE Delineation of focal infection is a major problem in the management of febrile granulocytopenic patients. The utility of indium-111-labeled human nonspecific immunoglobulin G (In-111-IgG), a newly developed radiopharmaceutical for imaging focal inflammation, was reported in patients with adequate WBC counts. In the present study, we investigated whether In-111-IgG scintigraphy could be used to locate infection in granulocytopenic patients. MATERIALS AND METHODS Granulocytopenic rats with focal infection were imaged after In-111-IgG injection. Thereafter, In-111-IgG scintigraphy was performed in 20 granulocytopenic patients. Images were obtained 4, 24, and 48 hours after injection of 75 mBq In-111-IgG. Scintigraphic findings were compared with clinical, roentgenologic, and ultrasonographic methods and culture results. RESULTS In the animal model high In-111-IgG accumulation was observed in the infectious focus. In the patients, 13 proven pulmonary, abdominal, joint, and soft tissue infections of both bacterial and fungal origin were detected adequately. In-111-IgG uptake not due to verified inflammation was observed in the large bowel of two patients. A thoracic wall infiltrate showing only mild inflammatory activity was not detected. Small toxoplasmosis lesions in heart, liver, and kidneys were obscured by physiologic In-111-IgG activity in these organs. CONCLUSIONS In-111-IgG scintigraphy is a useful technique to delineate focal infection in patients with granulocytopenia. Accumulation of the radiopharmaceutical does not appear to be granulocyte-mediated. In-111-IgG is a safe and convenient radiopharmaceutical that probably contributes to the early diagnosis of focal infection in granulocytopenic patients.
The role of NRF-2 and p38 MAPK on the function of human parenchymal fibroblasts
Authors: Anna Lagan, Nicola Green, Andrew Walker, Gisli Jenkins, Simon Johnson, Andrew Fisher, Alan Knox
Journal: European Respiratory Journal (2013)

Oxidative stress and chronic inflammation are key processes in COPD. Damage to the alveolar epithelium signals to fibroblasts to implement the repair process. Dysregulation in this process can lead to alveolar destruction as seen in emphysema. Sulforaphane (SFN) activates NRF-2 and upregulates antioxidant genes. VX745 inhibits p38MAPK and plays a role in cytokine production. Both are targets for the treatment of COPD. We hypothesised that the compounds would modify the response of parenchymal fibroblasts suffering exogenous stress.  Fibroblasts were grown from parenchymal explants. Confluent cells were serum starved for 24h, pre-treated with SFN & VX745 and stimulated with Cytomix (TNFα IFNγ IL-1β) +/- H 2 O 2 , IL-1 β, TNFα or TGFβ. IL-6 and IFNγ were detected in supernatant by ELISA. Collagen 1 & 3, Integrin β5 and β8 expression was quantitated by qPCR. Proliferation and apoptosis was assessed by BrdU incorporation and CaspACE3 assay. Cytomix+/- H2O2 induced IL-6 and IFNγ release into the supernatant. VX745 and SFN had no effect. IL-1β, TNFα and TGFβ induced IL-6. VX745 had a small inhibitory effect on all agonists but SFN was ineffective. Cytomix+/- H2O2 decreased collagen 1, 3 and Integrin β5 and β8 mRNA expression which was decreased further by SFN whereas VX745 exerted no effect. SFN inhibited proliferation and caused minor dose-dependent increase in apoptosis. VX745 limited proliferation and increased apoptosis at high doses.  There was no difference in responses to p38 inhibition or NRF-2 activation from normal fibroblasts and fibroblasts from patients with COPD. Neither the p38 nor the NRF-2 pathways are likely to be targets for modifying fibroblast function in COPD. On behalf of COPDMAP consortium.
Single-Layer Anastomosis in the Large Bowel: Ten Years' Experience
Authors: N A Matheson, D Valerio, A Farquharson, H Thomson
Journal: Journal of the Royal Society of Medicine (1981)

Satisfactory experience with single-layer colorectal anastomosis during 1969-74 led to an analysis of the results of single-layer large bowel anastomosis during the subsequent years 1975-79. This technique has continued to be associated with a low incidence of anastomotic failure, but anastomotic integrity also depends on rigorous attitudes to bowel preparation, to bacterial contamination and to the avoidance of anastomosis when the risk of anastomotic failure is high.
Smoking on celluloid
Authors: D. Carnall
Journal: BMJ (1998)

Douglas Carnall looks at the Health Education Authority's new campaign against tobacco in films

“The key moment of positive association of cigarettes with romance and desire is the final scene of Now, Voyager (1942), in which Paul Henreid lights two cigarettes and hands one to Bette Davis … marking the heroine's transition to sexual maturity—and the cigarette's to gender parity.”

The discourse of media studies has a distinctive literary flavour: what is new is its presence in the Health Education Authority's latest report. The results show that smoking on film is more prevalent than ever, though in the '90s it serves as dramatic shorthand for the portrayal of stress …
Loss of Gsα impairs liver regeneration through a defect in the crosstalk between cAMP and growth factor signaling
Authors: Changli Lu, Jie Xia, Yongjie Zhou, Xufeng Lu, Lei Zhang, Maling Gou, Lei Li, Xiaoyun Zhang, Hongjie Ji, Keting Zhu, Li Li, Jie Zhang, Ping Yu, Jiayin Yang, Hong Bu, Yujun Shi
Journal: Journal of Hepatology (2015)
Depression and adrenal function in spinal cord injury
Authors: Robert G Frank, Javad H. Kashani, Stephen A. Wonderlich, Alexander Lising, Luis R. Visot
Journal: American Journal of Psychiatry (1985)

Of 32 patients with spinal cord injury, 14 had a DSM-III diagnosis of depressive disorder: 12 had major depression (five with melancholia) and two were dysthymic. In those with major depression, a dexamethasone suppression test lacked sensitivity (30%) and specificity (50%).
Prostaglandins and cyclic AMP in epidermis.
Authors: KENJI ADACHI, KUNIHIKO YOSHIKAWA, KENNETH M. HALPRIN, VICTOR LEVINE
Journal: British Journal of Dermatology (1975)

Prostaglandins E1 and E2 stimulate cyclic AMP accumulation in pig epidermis and in human epidermis from patients with psoriasis. Prostaglandins A1, A2 and F2α are relatively ineffective. The fact that this stimulation is not inhibited by a β‐blocker (propranolol) and that the stimulation by prostaglandin E2 and adrenaline is additive indicates that each drug acts independently on the epidermal adenyl cyclase system. In other words, prostaglandins E1 and E2 act on a site other than the β‐receptor of adenyl cyclase in epidermis. The stimulation by prostaglandins E1 and E2 is not additive; hence they probably act on the same site. Concentrations of prostaglandin E above 3 × 10−7 M are effective in causing stimulation. This concentration may be within the physiological range and the contribution of endogenous prostaglandin levels in the control of intracellular cyclic AMP levels cannot be disregarded.