tbuckley/cabot-search huggingface dataset:
Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus
Authors: Peter A.B. Wark, Sebastian L. Johnston, Fabio Bucchieri, Robert Powell, Sarah Puddicombe, Vasile Laza-Stanca, Stephen T. Holgate, Donna E. Davies
Journal: The Journal of Experimental Medicine (2005)

Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects. Viral RNA expression and late virus release into supernatant was increased 50- and 7-fold, respectively in asthmatic cells compared with healthy controls. Virus infection induced late cell lysis in asthmatic cells but not in normal cells. Examination of the early cellular response to infection revealed impairment of virus induced caspase 3/7 activity and of apoptotic responses in the asthmatic cultures. Inhibition of apoptosis in normal cultures resulted in enhanced viral yield, comparable to that seen in infected asthmatic cultures. Examination of early innate immune responses revealed profound impairment of virus-induced interferon-β mRNA expression in asthmatic cultures and they produced &amp;gt;2.5 times less interferon-β protein. In infected asthmatic cells, exogenous interferon-β induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-β, impaired apoptosis and increased virus replication. These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.
Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial
Authors: S. Loi, S. Michiels, R. Salgado, N. Sirtaine, V. Jose, D. Fumagalli, P.-L. Kellokumpu-Lehtinen, P. Bono, V. Kataja, C. Desmedt, M.J. Piccart, S. Loibl, C. Denkert, M.J. Smyth, H. Joensuu, C. Sotiriou
Journal: Annals of Oncology (2014)
Functional roles of two polypeptide chains that compose an antigen-specific suppressor T cell factor.
Authors: M Taniguchi, T Tokuhisa, T Itoh, M Kanno
Journal: The Journal of Experimental Medicine (1984)

The functional roles of the two polypeptide chains that compose the T cell suppressor factor (TsF) that mediates the antigen-specific and genetically restricted suppressor function were studied by using the heavy or light chains isolated from the conventional TsF or the 11S and 13S mRNA translation products of TsF. Either the heavy or the light chain of mRNA translation products reconstitutes the active TsF that suppresses the antibody response in an antigen-specific and genetically restricted manner when it is combined with the isolated heavy or light chain from the conventional TsF. As a consequence, the antigen-binding heavy chain mediates the antigen specificity of TsF. On the other hand, the I-J-positive light chain works as an element to determine the genetic restriction specificity. Thus, the identity of the histocompatibility between the I-J haplotypes on the light chain and the responding cell is essential for the functional expression of TsF. No genetic preference, however, was observed, in the association of the heavy and light chains of TsF.
Reactions to Ephedrine
Authors: R. A. M. Scott
Journal: BMJ (1943)

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Attenuation of angiotensin II-mediated coronary vasoconstriction and vasodilatory action of angiotensin-converting enzyme inhibitor in pacing-induced heart failure in dogs
Authors: Yuji Oikawa, Kazuhira Maehara, Tomiyoshi Saito, Kazuaki Tamagawa, Yukio Maruyama
Journal: Journal of the American College of Cardiology (2001)
Performance of Primary Care Physicians and Other Providers on Key Process Measures in the Treatment of Diabetes
Authors: Fritha Morrison, Maria Shubina, Saveli I. Goldberg, Alexander Turchin
Journal: Diabetes Care (2012)

Studies have shown that patients without a consistent primary care provider have inferior outcomes. However, little is known about the mechanisms for these effects. This study aims to determine whether primary care physicians (PCPs) provide more frequent medication intensification, lifestyle counseling, and patient encounters than other providers in the primary care setting.This retrospective cohort study included 584,587 encounters for 27,225 patients with diabetes and elevated A1C, blood pressure, and/or LDL cholesterol monitored for at least 2 years. Encounters occurred at primary care practices affiliated with two teaching hospitals in eastern Massachusetts.Of the encounters documented, 83% were with PCPs, 13% were with covering physicians, and 5% were with midlevel providers. In multivariable analysis, the odds of medication intensification were 49% (P < 0.0001) and 26% (P < 0.0001) higher for PCPs than for covering physicians and midlevel providers, respectively, whereas the odds of lifestyle counseling were 91% (P < 0.0001) and 21% (P = 0.0015) higher. During visits with acute complaints, covering physicians were even less likely, by a further 52% (P < 0.0001), to intensify medications, and midlevel providers were even less likely, by a further 41% (P < 0.0001), to provide lifestyle counseling. Compared with PCPs, the hazard ratios for time to the next encounter after a visit without acute complaints were 1.11 for covering physicians and 1.19 for midlevel providers (P < 0.0001 for both).PCPs provide better care through higher rates of medication intensification and lifestyle counseling. Covering physicians and midlevel providers may enable more frequent encounters when PCP resources are constrained.
Creatine Transport in Brush-Border Membrane Vesicles Isolated from Rat Kidney Cortex
Authors: MARTA GARCÍA-DELGADO, MARÍA J. PERAL, MERCEDES CANO, MARÍA L. CALONGE, ANUNCIACIÓN A. ILUNDÁIN
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The kidney efficiently salvages creatine from the urine; however, the mechanism(s) that mediates renal creatine reabsorption has not been investigated. This study characterizes the creatine transport mechanism in brush-border membrane vesicles isolated from the rat renal cortex. An osmolality plot revealed that creatine is transported into an osmotically active space and that it is also bound to the membranes. An inwardly directed NaCl gradient stimulated creatine uptake and the time course of uptake exhibited an overshoot phenomenon, which indicates the presence of an active process for creatine in these membranes. The uptake of creatine showed an absolute requirement for both Na+ and Cl-. The NaCl gradient—dependent creatine uptake was stimulated by a valinomycin-induced, inside-negative, K+-diffusion potential, which suggests that the uptake process is electrogenic. Stoichiometric analyses indicated a probable couple ratio of 2 Na+:1 Cl-:1 creatine molecule. The kinetic study showed that creatine is transported by a high-affinity system (Km of 15 μM). Creatine uptake was inhibited by a 100-fold excess of various compounds with the following potency order: cold creatine = guanidinopropionic acid > nipecotic acid > γ-aminobutyric acid (GABA) = β-alanine = betaine, whereas carnitine, glycine, taurine, and choline were without effect. This pattern of inhibition differs from that observed for GABA uptake (unlabeled GABA = GPA > β-alanine > nipecotic acid ≫ creatine). The conclusion drawn was that the apical membrane of the renal cortical tubules contains an active, high-affinity, electrogenic, 2 Na+/1 Cl-/creatine cotransporter.
Prevalence of herpesviridae and hepatitis B virus DNA in the liver of patients with non-A, non-B fulminant hepatic failure
Authors: A Mason, R Sallie, R Perrillo, A Rayner, L Xu, D E Dohner, M Dehner, N Naoumov, L Gelb, B Saha, J O'Grady, R Williams
Journal: Hepatology (1996)

Members of the herpes virus family and hepatitis B virus (HBV) have been implicated as etiologic agents in non-A, non-B (NANB) fulminant hepatic failure (FHF), but the frequency of infection with these agents has not been established using appropriate controls. To examine this issue, we studied 50 NANB FHF patients and 104 liver transplant recipients from North America and Europe. Hepatic DNA was analyzed by polymerase chain reaction (PCR) for evidence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus I (HSV I) and II (HSV II), varicella-zoster virus (VZV), and human herpes virus-6 (HHV-6) nucleic acid sequences. The prevalence of HBV was assessed in North American subjects only. HSV I, HSV II, VZV, and HHV-6 viral sequences were not observed in any samples. Three of 50 FHF (6%) and 14 of 104 control patients (13%) were positive for CMV DNA. Two of 50 FHF (4%) and 10 of 104 control patients (10%) had EBV DNA, and HBV DNA was observed in 3 of 10 North American FHF patients (30%) and 3 of 59 controls (5%) without serum markers for HBV infection. The finding of HBV DNA in the liver of seronegative controls from North America but not Europe suggests that occult hepatitis B sequences in patients with NANB FHF may simply reflect geographic differences. The majority of cryptogenic FHF cases cannot be attributed to infection with herpes viruses or HBV.
Detection of Microbial Nucleic Acids for Diagnostic Purposes
Authors: N. Cary Engleberg, Barry I. Eisenstein
Journal: Annual Review of Medicine (1992)

The last decade has seen an explosion of interest in the use of molecular genetic techniques to diagnose infectious diseases. Specific molecular probes have been developed for nearly all of the significant, known microbial pathogens. The evolution of incrementally more powerful technologies, particularly gene amplification, has made it possible to detect pathogens with exquisite sensitivity, as well as specificity, based on their nucleic acids. As increasingly rapid and automated methods have become incorporated into successive generations of probe tests, these diagnostics have gained increasing acceptance for routine clinical use.
Implications of Apurinic/Apyrimidinic Endonuclease in Reactive Oxygen Signaling Response after Cisplatin Treatment of Dorsal Root Ganglion Neurons
Authors: Yanlin Jiang, Chunlu Guo, Michael R. Vasko, Mark R. Kelley
Journal: Cancer Research (2008)

Abstract Peripheral neuropathy is one of the major side effects of the anticancer drug cisplatin. Although previous work suggests that this neuropathy correlates with formation of DNA adducts in sensory neurons, growing evidence suggests that cisplatin also increases the generation of reactive oxygen species (ROS), which could cause DNA damage. Apurinic/apyrimidinic endonuclease/redox factor-1 (Ape1/Ref-1) is a multifunctional protein involved in DNA base excision repair of oxidative DNA damage and in redox regulation of a number of transcription factors. Therefore, we asked whether altering Ape1 functions would influence cisplatin-induced neurotoxicity. Sensory neurons in culture were exposed to cisplatin for 24 hours and several end points of toxicity were measured, including production of ROS, cell death, apoptosis, and release of the immunoreactive calcitonin gene–related peptide (iCGRP). Reducing expression of Ape1 in neuronal cultures using small interfering RNA (siRNA) enhances cisplatin-induced cell killing, apoptosis, ROS generation, and cisplatin-induced reduction in iCGRP release. Overexpressing wild-type Ape1 attenuates all the toxic effects of cisplatin in cells containing normal endogenous levels of Ape1 and in cells with reduced Ape1 levels after Ape1siRNA treatment. Overexpressing the redox deficient/repair competent C65-Ape1 provides partial rescue, whereas the repair-deficient Ape1 (N226A + R177A) does not protect neurons from cisplatin toxicity. We also observe an increase in phosphorylation of p53 after a decrease in Ape1 levels in sensory neuronal cultures. These results strongly support the notion that Ape1 is a potential translational target such that protecting Ape1 levels and particularly its DNA repair function could reduce peripheral neuropathy in patients undergoing cisplatin treatment. [Cancer Res 2008;68(15):6425–34]
A comparison between interferon gamma release assays and the tuberculin skin test in the contact tracing of patients with chronic kidney disease
Authors: D. W. Connell, A. Singanayagam, R. Charif, P. M. George, P. L. Molyneaux, C. McCrudden, M. Magtoto, E. Harden, S. L. Seneviratne, N. D. Duncan, O. M. Kon
Journal: Thorax (2010)

however, the ICDDR,B is the patent holder.Any potential financial gain will be for the Centre if/when this assay is commercialised.There are no other potential conflicts of interest related to the work presented.
Expansion of CCR5+ CD4+ T-lymphocytes in the course of active pulmonary tuberculosis
Authors: M.B. Santucci, M. Bocchino, S.K. Garg, A. Marruchella, V. Colizzi, C. Saltini, M. Fraziano
Journal: European Respiratory Journal (2004)

Nonsyncytium inducing, macrophage tropic HIV strains predominate in the course of active tuberculosis (TB). The present study assesses the expression of CCR5 in CD4+ T-lymphocytes from blood and bronchoalveolar lavage (BAL) of TB patients, non-TB lung disease controls and healthy controls. Memory (CD45RO+), recently activated (CD69+), proliferating (Ki67+) CCR5+ or CCR3+ CD4+ T-lymphocytes were determined by multiparametric flow cytometry analysis. Results show that BAL CD4+ T-lymphocytes expressing CCR5 or CCR3 were significantly increased when compared to peripheral blood both in patients and in healthy controls. However, the data show that the proportions of peripheral blood CCR5+ CD4+ and CCR3+ CD4+ T-lymphocytes and BAL CCR5+ CD4+ T-lymphocytes, but not BAL CCR3+ CD4+ T-lymphocytes, were significantly increased in TB patients. Furthermore, the observation that BAL CCR5+ CD4+ T-lymphocytes from TB patients expressed early activation markers, were not proliferating and showed down-regulation of CCR5 expression suggests recruitment and trapping at the site of disease. Altogether, these results suggest that the lower respiratory tract mucosa may provide cellular targets accessible for efficient transmission of macrophage tropic HIV-1 variants and that tuberculosis may enhance this phenomenon.
Clinical governance is unworkable
Authors: E N Grosch
Journal: British Journal of Sports Medicine (2004)

If you have a burning desire to respond to a paper published in BJSM, why not make use of our ''rapid response'' option?Log onto our website (www.bjsportmed.com), find the paper that interests you, and send your response via email by clicking on the ''eLetters'' option in the box at the top right hand corner.Providing it isn't libellous or obscene, it will be posted within seven days.You can retrieve it by clicking on ''read eLetters'' on our homepage. Mandatory wearing of helmets for elite cyclists: new perspectives in prevention of head injuriesCycling related injuries, especially those to the head, are common causes of morbidity, death, and disability and could largely be prevented by the proper use of hard shell helmets. 1 2 Unfortunately, obvious evidence is often not acknowledged, and the use of such a valuable preventive measure has been too long ignored.Media coverage of elite competitions, showing most athletes racing without helmets, has unfavourably influenced amateur and young cyclists for a long time.However, owing to the progressive increase in severe and fatal injuries, especially involving elite cyclists, and the evidence that the outcome of most of these tragedies might have been prevented, 1 2 the International Cycling Union announced that, from 5 May 2003, it is mandatory to wear a hard shell helmet in elite men's events for classes 4 and above.This decision was taken in agreement with the Professional Riders Association, who supported the initiative despite some internal differences of opinion.Images transmitted world wide during the 2003 Tour de France, a sporting event second in popularity only to the Olympics, are encouraging, showing all athletes wearing helmets throughout most of the race.This is a valuable message for both amateur cyclists and adolescents, as awareness is often more productive than restrictive measures.In addition, individual persuasion to wear helmets does not have the side effect of reducing the incentive to do cycling.Less cycling, in reaction to restrictive legislation, may counterbalance the beneficial effects on head injury prevention, as regular recreational aerobic activity, such as cycling, has manifest benefits on health, preventing the development of chronic disorders, including atherosclerosis, diabetes, osteoporosis, obesity, depression, and cancer.
Non-cystic fibrosis bronchiectasis in childhood: longitudinal growth and lung function
Authors: C M Bastardo, S Sonnappa, S Stanojevic, A Navarro, P M. Lopez, A Jaffe, A Bush
Journal: Thorax (2008)

Non-cystic fibrosis (non-CF) bronchiectasis often starts in childhood with a significant impact on adult morbidity. Little is known about disease progression through childhood and the effect on growth and spirometry. This study reviews longitudinal lung function and growth in children with non-CF bronchiectasis.The case notes of patients with non-CF bronchiectasis were reviewed retrospectively. Patients were included if at least three calendar years of lung function data were available. Anthropometric measurements and annual spirometry were analysed over both two and four consecutive years. Changes over time were assessed using Generalised Estimating Equations.Fifty-nine patients (31 boys) were identified. At baseline the median age was 8.2 years (range 4.8-15.8), the mean (SD) for height, weight and body mass index (BMI) for age z-scores were -0.68 (1.31), -0.19 (1.34) and 0.19 (1.38), respectively. At baseline, the mean (SD) z-score for forced expiratory volume in 1 s (FEV(1)) was -2.61 (1.82). Over 2 years (n = 59), mean FEV(1) and forced vital capacity (FVC) improved by 0.17 (95% CI 0.01 to 0.34, p = 0.039) and 0.21 (95% CI 0.04 to 0.39, p = 0.016) z-scores per annum, respectively. Over 4 years there was improvement in height-for-age z-scores (slope 0.05, 95% CI 0.01 to 0.095, p = 0.01) but no improvement in other anthropometric variables. There was no change in spirometry (FEV(1) slope 0.00, 95% CI -0.09 to 0.09, p = 0.999 and FVC slope 0.09, 95% CI -0.09 to 0.1, p = 0.859).Children with non-CF bronchiectasis show adequate growth over time. Lung function stabilises but does not normalise with treatment, underscoring the need for early detection and institution of appropriate therapy.
Preclinical Activity of the Rational Combination of Selumetinib (AZD6244) in Combination with Vorinostat in KRAS-Mutant Colorectal Cancer Models
Authors: M. Pia Morelli, John J. Tentler, Gillian N. Kulikowski, Aik-Choon Tan, Erica L. Bradshaw-Pierce, Todd M. Pitts, Amy M. Brown, Sujatha Nallapareddy, John J. Arcaroli, Natalie J. Serkova, Manuel Hidalgo, Fortunato Ciardiello, S. Gail Eckhardt
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Despite the availability of several active combination regimens for advanced colorectal cancer (CRC), the 5-year survival rate remains poor at less than 10%, supporting the development of novel therapeutic approaches. In this study, we focused on the preclinical assessment of a rationally based combination against KRAS-mutated CRC by testing the combination of the MEK inhibitor, selumetinib, and vorinostat, a histone deacetylase (HDAC) inhibitor. Experimental Design: Transcriptional profiling and gene set enrichment analysis (baseline and posttreatment) of CRC cell lines provided the rationale for the combination. The activity of selumetinib and vorinostat against the KRAS-mutant SW620 and SW480 CRC cell lines was studied in vitro and in vivo. The effects of this combination on tumor phenotype were assessed using monolayer and 3-dimensional cultures, flow cytometry, apoptosis, and cell migration. In vivo, tumor growth inhibition, 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET), and proton nuclear magnetic resonance were carried out to evaluate the growth inhibitory and metabolic responses, respectively, in CRC xenografts. Results: In vitro, treatment with selumetinib and vorinostat resulted in a synergistic inhibition of proliferation and spheroid formation in both CRC cell lines. This inhibition was associated with an increase in apoptosis, cell-cycle arrest in G1, and reduced cellular migration and VEGF-A secretion. In vivo, the combination resulted in additive tumor growth inhibition. The metabolic response to selumetinib and vorinostat consisted of significant inhibition of membrane phospholipids; no significant changes in glucose uptake or metabolism were observed in any of the treatment groups. Conclusion: These data indicate that the rationally based combination of the mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, selumetinib, with the HDAC inhibitor vorinostat results in synergistic antiproliferative activity against KRAS-mutant CRC cell lines in vitro. In vivo, the combination showed additive effects that were associated with metabolic changes in phospholipid turnover, but not on FDG-PET, indicating that the former is a more sensitive endpoint of the combination effects. Clin Cancer Res; 18(4); 1051–62. ©2011 AACR.