tbuckley/cabot-search huggingface dataset:
Predictors of asthma symptom remission after five years of age
Authors: Steve Turner, Nanda Prabhu, Rebecca Cutts, Keith Allen, Peter Helms, Anthony Seaton, Graham Devereux
Journal: European Respiratory Journal (2011)

Introduction:  Childhood asthma is a common condition characterised by relapse and remission. Here we sought to identify the precision of physiological measurements made in 5-year-olds for predicting asthma outcome at 10 years of age.   Methods:  As part of a cohort study, 5 year old children attended a clinical assessment which included skin prick reactivity, spirometry and bronchodilator response. A respiratory symptom questionnaire was completed at ages 5 and 10 years. Children were categorised as having persistent asthma, early remittent asthma, later onset asthma or being non-asthmatic.   Results:  Of the 1924 originally recruited, questionnaire data were available in 808 children at both 5 and 10 years of age including 37 with persistent asthma, 30 with early remittent asthma and 33 with later onset asthma. Skin prick reactivity was determined in 483 5-year-olds, spirometry in 410, bronchodilator response (BDR) in 164 and FE NO  in 110. Atopy had sensitivity of 82% [95% CI 68, 92] and specificity of 57% [95% CI 42, 68] for predicting persistent asthma in symptomatic 5–year-olds and a sensitivity of 72% [95% CI 50, 87%] and specificity of 79% [95% CI 78-80] for predicting later onset asthma in asymptomatic 5-year-olds. Regardless of asthma status at 5 years, FE NO  >10.7ppb had a sensitivity of 62% and specificity of 89% for asthma at 10 years. Spirometry and BDR were not predictive of later asthma outcomes   Conclusions:  In this community-based cohort, objective physiological measurements taken in 5-year-olds were able to predict asthma outcome in later childhood. The absence of atopy or elevated FE NO  in a young child with asthma or asthma-like symptoms may be helpful in predicting low risk for future asthma symptoms.
Distribution of vitamin C transporters in the lower airways of humans
Authors: G.D. Rankin, N. Larsson, E. Roos-Engstrand, J. Pourazar, A. Blomberg, I. Mudway, A.F. Behndig
Journal: European Respiratory Journal (2013)

Vitamin C (ascorbate, AscH2 + dehydroascorbate, DHA) is an important low-molecular weight antioxidant at the air-lung interface. Despite its critical role, little is known about its transport and the regulation of intra-cellular concentrations in the lung. Whilst several vitamin C transporters are identified, such as sodium-ascorbate co-transporters (SVCT1/2) and glucose transporters (GLUTs), the latter transporting the AscH2 oxidation product DHA, knowledge of their presence and distribution in the human lung is limited (GLUTs) or unknown (SVCTs).

We hypothesised that these transporters are present within the bronchial airways and play a vital role in the regulation of epithelial and respiratory tract lining fluid vitamin C concentrations.

We investigated the distribution of these transporters in endobronchial biopsies obtained by bronchoscopy from 16 mild asthmatics and 16 age-matched healthy controls.

Positive staining was found in blood vessels for SVCT1 and 2; with SVCT 2 and GLUT2 also present in the apical epithelium. Staining with GLUT1 yielded a distinct cell membrane staining. There were no apparent differences between asthmatics and controls. SVCT2 staining was further shown to be predominately localised to goblet cells. SVCT2+goblet cells were negatively correlated with total vitamin C concentrations determined in the bronchial wash of these subjects (ρ=-0.661, p<0.05).

This is the first study to demonstrate that SVCT2 is present in the human lung epithelium, localised mainly within goblet cells. The negative correlation between SVCT2+goblet cells and vitamin C suggests that these cells may play a hitherto unknown function in vitamin C re-uptake and recycling at the air-lung interface.
Cyclosporine promotes glomerular endothelin binding in vivo.
Authors: M Awazu, M Sugiura, T Inagami, I Ichikawa, V Kon
Journal: Journal of the American Society of Nephrology (1991)

It has previously been shown that administration of cyclosporine causes a prompt (within 15 min after infusion) increase in circulating level of endothelin 1 and a pattern of glomerular hypoperfusion and hypofiltration which can be ameliorated with antiendothelin antibody. We now show that 60 min after cyclosporine, serum endothelin 1 level falls to less than 2.55 +/- 0.31 pg/mL (N = 6), a value comparable to that found in normal animals (less than 2 pg/mL). The study presented here also examines whether sustained cyclosporine-induced glomerular dysfunction is associated with altered endothelin receptor characteristics. Saturation and competitive inhibition binding studies in isolated glomerular membranes showed two binding sites. Of these, the density of the low-affinity site was affected by cyclosporine treatment (851 +/- 117 versus 425 +/- 61 fmol/mg of protein; P less than 0.05; N = 6) without a change in equilibrium dissociation constant, KD. The high-affinity site was not affected. The receptor characteristics of another vasoconstrictor, angiotensin II, were not affected by cyclosporine. In addition, there was no difference in endothelin binding sites in hepatic tissue between cyclosporine and control rats. These results raise the intriguing possibility that cyclosporine-induced glomerular dysfunction involves upregulation of endothelin binding sites and that altered endothelin receptors appear specific to the kidney.
Detection of Acquired Provirus Sequences in Mammary Tumors From Low-Expressor, Low-Risk Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Bruce W. Altrock, Robert D. Cardiff, John P. Puma, Judi K. Lund
Journal: JNCI Journal of the National Cancer Institute (1982)

Murine mammary tumor virus (MuMTV) provirus sequences in the DNA from early-occurring (average age 10 mo) and late occurring (age greater than 20 mo) tumors in BALB/cfC3H mice were analyzed by Eco RI restriction endonuclease mapping procedures. All early tumors were MuMTV antigen-positive mammary adenocarcinomas that contained the 0.92- and 4.0-kilo base (kb) exogenous C3H MuMTV-specific Pst I restriction endonuclease fragments. All but 1 of the late mammary adenocarcinomas had MuMTV antigens detected by peroxidase antiperoxidase staining, and all contained the 0.92- and 4.0-kb exogenous virus Pst I fragments. Three late nonmammary tumors lacked both MuMTV antigens and acquired provirus sequences. Greater numbers of MuMTV sequences were detected in both early and late-arising mammary tumors by Eco RI restriction endonuclease mapping than were detected in tissues from uninfected BALB/c mice. However, neither the number nor the location of MuMTV proviruses correlated with tumor latent period.
Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study
Authors: Jakob A. Østergaard, Steffen Thiel, Maria Lajer, Rudi Steffensen, Hans-Henrik Parving, Allan Flyvbjerg, Peter Rossing, Lise Tarnow, Troels K. Hansen
Journal: Diabetes Care (2015)

Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore aimed to investigate this.We studied an existing 12-year prospective cohort with type 1 diabetes with 198 patients with diabetic nephropathy (121 men, age 41 years [95% CI 40-42], estimated glomerular filtration rate [eGFR] 67 mL/min/1.73 m(2) [95% CI 63-70]) and 174 normoalbuminuric patients (103 men, age 43 years [95% CI 41-44], eGFR 93 mL/min/1.73 m(2) [95% CI 91-95]). Mortality rates were compared according to the concentration-determining MBL2 genotype or the MBL concentration. Patients were classified as having high or low MBL expression genotypes. The effect of MBL concentration was estimated by comparing patients with MBL concentrations above or below the median.Ninety-eight patients died during follow-up. The unadjusted hazard ratio (HR) for all-cause mortality was 1.61 (95% CI 1.07-2.43) for patients with high MBL expression genotypes versus patients with low MBL expression genotypes (P = 0.023). All-cause mortality was higher in patients with MBL concentrations above the median than in patients with MBL concentrations below the median (unadjusted HR 1.90 [95% CI 1.26-2.87], P = 0.002).High MBL expression genotypes and high MBL concentrations are both associated with increased mortality rates in type 1 diabetes compared with low MBL expression genotypes and low MBL concentrations.
Bicalutamide for advanced prostate cancer: the natural versus treated history of disease.
Authors: H I Scher, C Liebertz, W K Kelly, M Mazumdar, C Brett, L Schwartz, G Kolvenbag, L Shapiro, M Schwartz
Journal: Journal of Clinical Oncology (1997)

To determine the therapeutic effects of bicalutamide 200 mg in patients with prostate cancers of different hormone sensitivities.Patients with progressive prostate cancer were treated with bicalutamide 200 mg daily. Before treatment, patients' tumors were classified on the basis of prior hormone exposure and by serum testosterone levels into androgen-dependent and androgen-independent groups. Prior exposure to flutamide and response to flutamide withdrawal was also considered. Outcomes were reported independently on the basis of posttherapy changes in prostate-specific antigen (PSA), measurable disease, and radionuclide bone scans.Outcomes varied by prior hormone exposure as a higher proportion of patients with progression of androgen-dependent tumors showed posttherapy PSA decreases of more than 50% or more than 80%, measurable disease regression, and improvement on radionuclide bone scans than did patients with androgen-independent progression. Within the category of androgen-independent progression, clinical benefit was observed in patients who had previously progressed on flutamide, independent of the response to flutamide withdrawal. Patients who had progressed on a gonadotropin-releasing hormone (GnRH) analog alone had a low response proportion, whereas those who progressed after two or more hormone therapies did not respond. Overall, the drug was well tolerated. After progression on bicalutamide monotherapy, one third of patients with androgen-dependent progression responded to medical castration with a GnRH analog.Classifying patient tumors on the basis of prior hormone exposure permits a more precise estimate of the potential benefit of a specific hormone therapy for the individual patient. The precision is further increased by reporting the effects of a drug on each parameter of disease independently. The difference in outcomes for patients with androgen-independent progression suggests that the specific hormone therapy administered and the response to that therapy can influence the biology of the relapsing tumor and the sensitivity to subsequent therapies. The sensitivity to bicalutamide after progression on flutamide deserves further study.
Prospective Evaluation of Paclitaxel Versus Combination Chemotherapy With Fluorouracil, Doxorubicin, and Cyclophosphamide as Neoadjuvant Therapy in Patients With Operable Breast Cancer
Authors: Aman U. Buzdar, S. Eva Singletary, Richard L. Theriault, Daniel J. Booser, Vicente Valero, Nuhad Ibrahim, Terry L. Smith, Lina Asmar, Debra Frye, Nikki Manuel, Shu-Wan Kau, Marsha McNeese, Eric Strom, Kelly Hunt, Frederick Ames, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To compare prospectively the antitumor activity of single-agent paclitaxel to the three-drug combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC) as neoadjuvant therapy in patients with operable breast cancer. PATIENTS AND METHODS: Patients with T1-3N0-1M0 disease were randomized to receive either paclitaxel (250 mg/m 2 ) as 24-hour infusion or FAC in standard doses at every-3-week intervals. Each patient was treated with four cycles of preoperative chemotherapy. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after four cycles of induction chemotherapy. RESULTS: A total of 174 patients were registered, and 87 were randomized to each arm of the study. Clinical response, ie, complete and partial responses, was similar in both arms of the study. Three patients in the FAC arm and one patient in the paclitaxel subgroup had progressive disease. The extent of residual disease by intent-to-treat analysis at the time of surgery was similar between the two arms of the study. CONCLUSION: The results of this prospective study demonstrated that single-agent paclitaxel as neoadjuvant therapy has significant antitumor activity, and this was clinically comparable to FAC. Similar fractions of patients had clinical complete and partial responses, and very few patients had no response to either therapy. The value of alternate non–cross-resistant therapies as used in this protocol on the clinical course of this disease would require longer follow-up.
Unexpected encephalopathy in chronic renal failure
Authors: J L Pimentel, S W Brusilow, W E Mitch
Journal: Journal of the American Society of Nephrology (1994)

A woman with mild chronic renal insufficiency was being treated with glucocorticoids for a presumed chronic inflammatory disease. She developed peritonitis arising from a pelvic abscess, which was drained without complications. Unexpectedly, she became obtunded, and eventually, the neurologic dysfunction was linked to hyperammonemia in spite of normal liver function tests. Hyperammonemia was only transiently controlled in spite of protein restriction, repeated hemodialysis, and the use of biochemical means to reduce ammonia. A recurrent pelvic abscess was drained, and hyperammonemia disappeared. A review of ammonia and nitrogen metabolism indicates that bypassing the liver with shunting of ammonia into the systemic circulation should be added to the causes of symptomatic hyperammonemia. Treatment requires the elimination of the bacteria.
Pulmonary emphysematous dysplasia in young adults
Authors: Stanislav Gorbunkov, Olga Lukina, Larisa Kirukhina, Andrey Akopov
Journal: European Respiratory Journal (2011)

Objective:  Therapeutic approach to the treatment of young patients with severe pulmonary emphysema is not specified.   Method:  From 2004 to 2010 eight patients of young age (24 to 33 years old) with pulmonary emphysema and respiratory failure were observed. All patients were heavy smokers with over a seven pack-years smoking history. All patients were diagnosed with florid irreversible respiratory system changes (average FEV1 23% predicted) with significant hyperinflation (average RV 380% predicted), sharp reduction of diffusing capacity (average DLCO 32% predicted) and blood gases disorder. No alpha 1-antitrypsin deficiency revealed.   Results:  Unilateral LVRS was performed via standard thoracotomy in five patients. Four of the patients had no postoperative complications. One patient suffered postoperative respiratory failure caused by bronchitis exacerbation which required extended use of artificial respiration in postoperative period. A year after the surgery all patients noticed surgical treatment9s positive effect on exercise tolerance and clinical disease progression. None of the patients who undergone surgery had any bacterial exacerbation of the disease, was hospitalized and underwent antibacterial therapy. Dyspnea evaluation tests revealed significant improvements among all operated patients persisting during three years follow-up.   Conclusion:  LVRS performed in young adults has same functional effect as in COPD patients but clinical progression in early postoperative period is more favorable. Because of patients9 young age, in case of impossibility of lung transplantation LVRS is medically justified.
Factors Affecting Mortality From Secondary Disease in Mouse Radiation Chimeras2
Authors: C. C. Congdon, M. A. Kastenbaum, D. A. Gardiner
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Factors Affecting Mortality From Secondary Disease in Mouse Radiation Chimeras Get access C. C. Congdon, C. C. Congdon Biology and Mathematics Divisions, Oak Ridge National Laboratory, Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar M. A. Kastenbaum, M. A. Kastenbaum Biology and Mathematics Divisions, Oak Ridge National Laboratory, Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar D. A. Gardiner D. A. Gardiner Biology and Mathematics Divisions, Oak Ridge National Laboratory, Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 35, Issue 1, July 1965, Pages 227–234, https://doi.org/10.1093/jnci/35.1.227 Published: 01 July 1965 Article history Received: 05 April 1965 Published: 01 July 1965
Mutagenicity of Tris(2,3-dibromopropyl) Phosphate in Mammalian Gonad and Bone Marrow Tissue&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Michael F. Salamone, Roxanne Holdbrook, Morris Katz
Journal: JNCI Journal of the National Cancer Institute (1981)

The mutagenic and clastogenic (chromosome breaking) effects of the flame retardant Tris(2,3-dibromopropyl) phosphate (Tris-BP) were investigated in two mammalian in vivo assays, the bone marrow micronucleus test and the abnormal sperm head assay. Two potency of Tris-BP was determined in the Salmonella-mammalian microsome assay. Tris-BP was mutagenic in all three assays, in both mammalian tests, nearly toxic doses were required in B6C3F mice for positive mutagenic and clastogenic results. In the micronucleus test, Tris-BP was a weak clastogen, whereas in the abnormal sperm head assay, Tris-BP was observed to be strongly mutagenic. The abnormal sperm head data might imply genetic damage to germ tissue. The data suggested a means for possibly monitoring Tris-BP exposure. Thus besides being a strong mutagen on bacterial systems, Tris-BP was also a weak clastogen as detected in bone marrow cells and was a mutagen to gonad tissue.
Abstract 2438: Complications Increase Mortality Risk After De Novo Implantion of a Cardioverter Defibrillator: Initial Findings From the Ontario ICD Database
Authors: Douglas S Lee, Andrew D Krahn, Jeffrey S Healey, David Birnie, Eugene Crystal, Paul Dorian, Christopher S Simpson, Yaariv Khaykin, Douglas Cameron, Amir Janmohamed, Raymond Yee, Zhongliang Chen, Judy Hardy, Jack Tu
Journal: Circulation (2009)
Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy
Authors: Claire Gueguen, Julien Bouley, Hélène Moussu, Sonia Luce, Magalie Duchateau, Julia Chamot-Rooke, Marc Pallardy, Vincent Lombardi, Emmanuel Nony, Véronique Baron-Bodo, Laurent Mascarell, Philippe Moingeon
Journal: Journal of Allergy and Clinical Immunology (2015)
Effect of combining nicotinamide as a PARS-inhibitor with selective iNOS blockade during porcine endotoxemia
Authors: A. Stehr, F. Ploner, I. Tugtekin, M. Matejovic, M. Theisen, C. Zülke, M. Georgieff, P. Radermacher, K.-W. Jauch
Journal: Intensive Care Medicine (2003)
Modeling resolution of direct acute lung injury
Authors: Brijesh Patel, Michael Wilson, Masao Takata
Journal: European Respiratory Journal (2011)

Translational animal models allowing the study of both inflammatory and resolution phases of acute lung injury (ALI) are lacking. Widely used models including intratracheal endotoxin or bleomycin are difficult to translate. Here we developed and optimized a reproducible model of resolving aspiration pneumonitis that mimics human ALI.  C57Bl6 mice were instilled intratracheally with 75μl of 0.1M hydrochloric acid by direct laryngoscopy under anesthesia. At specified timepoints up to 10 days after instillation, respiratory mechanics, arterial blood gases, soluble mediators in bronchoalveolar lavage fluid (BALF), and alveolar fluid clearance (AFC) using an in situ preparation were measured. Acid instillation produced significant increases in BALF protein levels and respiratory elastance. BALF levels of TNF and soluble RAGE, a marker of epithelial damage, both increased, while AFC deteriorated. All of these injury parameters peaked at days 1-3 post-acid, but resolved by days 5-10.  These results indicate that the model replicates major hallmarks of ALI, i.e. changes in respiratory mechanics, gas exchange, lung permeability, inflammation and AFC, but shows full resolution. This model will allow future investigation of novel resolving pathways.  Supported by the Wellcome Trust.
Abstract 183: Branched-Chain Amino Acid Catabolic Reprogramming in Heart Failure
Authors: Haipeng Sun, Kristine Olson, Chen Gao, Domenick A Prosdocimo, Meiyi Zhou, Darwin Jeyaraj, Ji-Youn Youn, Shuxun Ren, Hua Cai, Peipei Ping, Paul C Schulze, Christopher Lynch, Mukesh K Jain, Yibin Wang
Journal: Circulation Research (2014)

Abnormal branched-chain amino acids (BCAA) catabolism has been strongly linked with cardiovascular and metabolic diseases in recent studies. In heart, metabolic reprogramming associated with the onset of heart failure has been established based on fetal-like changes in fatty acid and glucose metabolism, while little is known about the changes in amino acid homeostasis. In this report, we demonstrated a signature of suppressed BCAA catabolism in failing rodent and human hearts. The branched-chain α-keto acids (BCKA), intermediate of BCAA catabolism, accumulates, closely coordinated with reduced expression of key enzymes of BCAA catabolism in pathologically stressed myocardium. The down-regulation of these genes mimics a similar expression pattern observed in neonatal heart, indicating a fetal-like genetic reprogramming. Using both in vitro and in vivo models, we identified KLF15 as a key transcriptional regulator of the BCAA catabolic circuitry in heart. Genetic inactivation of BCAA catabolic pathway resulted in elevated cardiac BCKA levels and promoted cardiac dysfunction in response to mechanical overload, associated with increased oxidative stress and impaired mitochondrial respiration. Taken together, our data established for the first time that BCAA catabolic reprogramming is an integral component of metabolic remodeling that contributes to heart failure progression.