tbuckley/cabot-search huggingface dataset:
Bronchial responsiveness to hyperventilation in children with asthma: inhibition by ipratropium bromide.
Authors: N Wilson, C Dixon, M Silverman
Journal: Thorax (1984)

Isocapnic hyperventilation dose response curves were constructed for 11 asthmatic children before and after pretreatment with placebo or ipratropium bromide, 40-1500 micrograms given by inhalation, on three separate days. The response before and after placebo was highly reproducible (within subject coefficient of variation 7.5%, 18%, and 22% for intervals of two hours, within two weeks, and over two weeks). It was independent of baseline lung function. Complete protection against hyperventilation induced asthma was achieved by ipratropium bromide 40 micrograms in six children and by 200 micrograms or more in a further four. The remaining child was unaffected by any dose of ipratropium up to 1500 micrograms. The dose of ipratropium required for protection was better related to the subjects9 requirement for regular medication than to their sensitivity to hyperventilation or baseline lung function.
Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin
Authors: Karla L Lightfield, Jenny Persson, Sky W Brubaker, Chelsea E Witte, Jakob von Moltke, Eric A Dunipace, Thomas Henry, Yao-Hui Sun, Dragana Cado, William F Dietrich, Denise M Monack, Renée M Tsolis, Russell E Vance
Journal: Nature Immunology (2008)
Augmentation of umbilical cord blood (UCB) transplantation with ex vivo–expanded UCB cells: results of a phase 1 trial using the AastromReplicell System
Authors: Jennifer Jaroscak, Kristin Goltry, Alan Smith, Barbara Waters-Pick, Paul L. Martin, Timothy A. Driscoll, Richard Howrey, Nelson Chao, Judy Douville, Sue Burhop, Pingfu Fu, Joanne Kurtzberg
Journal: Blood (2003)
Age, Period, and Cohort Effects: Influences on Differences between Cross-sectional and Longitudinal Pulmonary Function Results
Authors: Michael D. Lebowitz
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

"Age, Period, and Cohort Effects: Influences on Differences between Cross-sectional and Longitudinal Pulmonary Function Results." American Journal of Respiratory and Critical Care Medicine, 154(6_pt_2), pp. S273–S277
Relationship Between Homocysteine and Mortality in Chronic Kidney Disease
Authors: Vandana Menon, Mark J. Sarnak, Tom Greene, Xuelei Wang, Arema A. Pereira, Gerald J. Beck, John W. Kusek, Jacob Selhub, Allan J. Collins, Andrew S. Levey, Michael G. Shlipak
Journal: Circulation (2006)

The relationship between total homocysteine (tHcy) and outcomes has not been investigated in patients with chronic kidney disease stages 3 to 4.The Modification of Diet in Renal Disease Study was a randomized, controlled trial of 840 patients. Serum tHcy was measured in frozen samples collected at baseline (n=804). Survival status and cause of death were obtained from the National Death Index. To evaluate its association with all-cause and cardiovascular disease (CVD) mortality, tHcy was evaluated both as tertiles (<14.7, 14.7 to 19.5, > or =19.6 micromol/L) and as a continuous variable (per 10/micromol/L). Participants had a mean age of 52+/-12 years and glomerular filtration rate (GFR) of 33+/-12 mL/min per 1.73 m2; 60% were male, and 85% were white. During a median follow-up of 10 years, 195 (24%) died from any cause, and 118 (15%) from CVD. The level of GFR was lower and proteinuria higher in the highest tHcy tertile. There was no association between the highest tertile of tHcy and all-cause (hazard ratio [HR]; 95% confidence interval [CI[, 1.32, 0.94 to 1.85) or CVD (HR; 95% CI, 1.50, 0.96 to 2.34) mortality in univariate analyses; this association was further attenuated by adjustment for GFR (HR; 95% CI all-cause, 1.04, 0.72 to 1.51; CVD, 1.20, 0.73 to 1.95). There was no association between tHcy as a continuous variable and all-cause (0.98, 0.83 to 1.16) or CVD (1.04, 0.85 to 1.27) mortality.Hyperhomocystinemia does not appear to be a risk factor for all-cause or CVD mortality in the Modification of Diet in Renal Disease Study. Prior studies demonstrating an association between tHcy and CVD risk may have inadequately adjusted for the confounding effects of kidney function.
Patterns of failure following local excision and local excision and postoperative radiation therapy for invasive rectal adenocarcinoma.
Authors: C G Willett, J E Tepper, S Donnelly, W C Wood, P C Shellito, G V Rodkey, M A Stracher, C C Compton
Journal: Journal of Clinical Oncology (1989)

The clinical course of 40 patients undergoing conservative surgical excision and 26 patients undergoing local excision and postoperative radiation therapy of rectal carcinoma was reviewed. Surgical procedures were transanal excision (55 patients), Kraske procedure (ten patients), and fulguration (one patient). The five-year actuarial survival, disease-free survival, and local control of all 66 patients were 70%, 77%, and 63%, respectively. For patients undergoing local excision alone, the prognostic features of lesion size greater than 3 cm, poorly differentiated histology, invasion into muscularis propria or deeper, moderate to marked stromal fibrosis, vascular or lymph vessel invasion, fragmented resection, and positive resection margins were associated with a local failure rate of 20% or greater. Of the 26 patients receiving postoperative radiation therapy, four patients have developed local failure. For subgroups of patients with small rectal carcinomas confined to the mucosa, local excision may be a reasonable alternative to abdominoperineal resection. For tumors with deeper invasion but limited to the bowel wall, local excision plus pelvic irradiation can be offered to preserve anorectal function.
Beneficial Effects on Skeletal Muscle of the Angiotensin II Type 1 Receptor Blocker Irbesartan in Experimental Heart Failure
Authors: Luciano Dalla Libera, Barbara Ravara, Annalisa Angelini, Katia Rossini, Marco Sandri, Gaetano Thiene, Giovanni Battista Ambrosio, Giorgio Vescovo
Journal: Circulation (2001)

Background —In congestive heart failure (CHF), skeletal muscle shows increased expression of fast myosin heavy chains (MHC) and fibers, muscle atrophy, increased fatigability, and decreased endurance. Atrophy is secondary to myocyte apoptosis, which is probably triggered by tumor necrosis factor-α (TNFα). Angiotensin II receptors are thought to play a role in controlling apoptosis. We tested the hypothesis that angiotensin II receptor blockade could prevent skeletal muscle apoptosis in rats with CHF. Methods and Results —CHF was induced by injecting 36 rats with 30 mg/kg monocrotaline. Ten additional animals were injected with saline and acted as controls. After 2 weeks, 18 of the 36 rats with CHF were treated with 7 mg · kg –1 · d –1 irbesartan through osmotic minipumps, and 10 of the 36 rats were treated with 2 mg · kg –1 · d –1 nifedipine in drinking water. After 2 additional weeks, rats were killed. Tibialis anterior cross-sectional area, MHC composition, myocyte apoptosis, Bcl-2, pro-caspase 3, and activated caspases 3 and 9 were determined, as were plasma levels of TNFα and angiotensin II. Myocyte apoptosis and muscle atrophy were significantly decreased with irbesartan compared with untreated CHF rats. Irbesartan-treated rats had fewer cells labeled positively with terminal deoxynucleotidal transferase–mediated dUTP nick-end labeling and fewer caspases; however, they also had increased Bcl-2 levels and muscle fiber cross-sectional areas. The MHC pattern in irbesartan-treated animals was similar to that in controls. Nifedipine animals behaved like the untreated CHF animals. Angiotensin II was increased 3- to 4-fold in all CHF rats (treated and untreated). TNFα levels were decreased in irbesartan-treated rats but not in nifedipine-treated rats. Conclusions —Angiotensin II receptor blockade can protect from the development of apoptosis-dependent atrophy and from changes in MHCs. The reduction of TNFα may play a role in this process.
Cutaneous vasculitis developed in a patient with breast cancer undergoing aromatase inhibitor treatment
Authors: H Shoda, S Inokuma, N Yajima, Y Tanaka, K Setoguchi
Journal: Annals of the Rheumatic Diseases (2005)

In conclusion, infliximab can be used safely in daily clinical practice, but both doctors and patients should be aware of the (infection) risks, especially in patients receiving a higher dose (.3 mg/kg) of infliximab, in order to anticipate and minimise these risks.
PhiC31/PiggyBac modified stromal stem cells: effect of interferon γ and/or tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on murine melanoma
Authors: Vahid Bahrambeigi, Nafiseh Ahmadi, Stefan Moisyadi, Johann Urschitz, Rasoul Salehi, Shaghayegh Haghjooy Javanmard
Journal: Molecular Cancer (2014)

TRAIL and IFNγ are promising anti-cancer cytokines and it has been shown that IFNγ may sensitize cancer cells to TRAIL. Adipose derived mesenchymal stem cells (ADSCs) are attractive vehicles for delivering anti-cancer agents. In this study, we evaluated the therapeutic potential of PhiC31 (φC31) recombinase and/or piggyBac transposase (pBt) modified ADSCs expressing either TRAIL, IFNγ, or co-expressing TRAIL/IFNγ in mouse models of melanoma. The expression and bioactivity of mouse IFNγ and TRAIL in φC31 and pBt modified cells were confirmed. We examined the effects of modified ADSCs on signal intensity of red fluorescence protein expressed by melanoma cells in subcutaneous tumors or established lung metastases and on survival (6 mice per group). We also conducted a flow cytometric analysis of systemic CD4+CD25+FOXP3+ T regulatory cells (Tregs) and histological analysis of melanoma tumors. Data were analyzed by Student t test, ANOVA, and log-rank tests. All statistical tests were two-sided. We demonstrated non-viral DNA-integrating vectors can be used for stable transgene expression. IFNγ inhibited melanoma cell growth in vitro probably via IFNγ-induced JAK/STAT1 signaling pathway activation. Murine TRAIL induced apoptosis in the human cell lines CAOV-4 and Ej-138, while MCF7 and B16F10 cells appeared to be insensitive to TRAIL. Treatment of melanoma cells with IFNγ did not influence their response to TRAIL. In contrast, results from in vivo studies showed that IFNγ-expressing ADSCs, engrafted into tumor stroma, inhibited tumor growth and angiogenesis, prevented systemic increase of Tregs, increased PD-L1 expression and CD8+ infiltration (but not interleukin-2+ cells), and prolonged the survival of mice (68 days, 95% confidence interval [CI] =52 to 86 days compared to 36 days, 95% CI =29 to 39 days for control, P < .001). For the first time, we employed DNA integrating vectors for safe and stable modification of MSCs. Our data indicate potential of non-virally modified IFNγ-expressing ADSCs for treatment of melanoma through direct effects of IFNγ. This study may have a significant role in the management of cancer in the future.
Misconceptions About Diabetes and Its Management Among Low-Income Minorities With Diabetes
Authors: Devin M. Mann, Diego Ponieman, Howard Leventhal, Ethan A. Halm
Journal: Diabetes Care (2009)

OBJECTIVE To determine diabetic patients' knowledge and beliefs about the disease and medications that could hinder optimal disease management. RESEARCH DESIGN AND METHODS A cross-sectional survey of 151 type 2 diabetic patients characterizing diabetes knowledge and beliefs about the disease and medications was conducted. RESULTS Mean diabetes duration was 13 years. Over half of the patients (56%) believed that normal glucose is ≤200 mg/dl, 54% reported being able to feel when blood glucose levels are high, 36% thought that they will not always have diabetes, 29% thought that their doctor will cure them of diabetes, one in four (23%) said there is no need to take diabetes medications when glucose levels are normal, and 12% believed they have diabetes only when glucose levels are high. CONCLUSIONS Diabetes knowledge and beliefs inconsistent with a chronic disease model of diabetes were prevalent in this sample. Suboptimal knowledge and beliefs are potentially modifiable and are logical targets for educational interventions to improve diabetes self-management.
Epidemiology of Chlamydia trachomatis infection in women and the cost-effectiveness of screening
Authors: J.A. Land, J.E.A.M. Van Bergen, S.A. Morre, M.J. Postma
Journal: Human Reproduction Update (2009)

The majority of Chlamydia trachomatis infections in women are asymptomatic, but may give rise to pelvic inflammatory disease (PID) and tubal infertility. Screening programmes aim at reducing morbidity in individuals by early detection and treatment, and at decreasing the overall prevalence of infection in the population. A number of modelling studies have tried to calculate the threshold prevalence of chlamydia lower genital tract infection above which screening becomes cost-effective. There is considerable debate over the exact complication rates after chlamydia infections, and more precise estimates of PID and tubal infertility are needed, for instance to be inserted in economic models. With reference to key studies and systematic reviews, an overview is provided focusing on the epidemiology of chlamydia infection and the risk-estimates of its late complications. In the literature, the generally assumed risk of developing PID after lower genital tract chlamydia infection varies considerably, and is up to 30%. For developing tubal infertility after PID the risks are 10–20%. This implies that the risk of test-positive women of developing tubal infertility would range between 0.1 and 6%. We included chlamydia IgG antibody testing in a model and estimated a risk of tubal infertility up to 4.6%. The risk of developing late complications after chlamydia lower genital tract infection appears low. High quality RCTs dealing with the transition from cervicitis to infertility are needed to broaden the evidence. In screening programmes, chlamydia antibody testing, as an intermediate marker for potential adverse sequelae, might enable more precise estimates.
Transposition of the Great Arteries
Authors: Carole A. Warnes
Journal: Circulation (2006)

Many patients with ventriculoarterial discordance have survived to adulthood. Those with complete transposition of the great arteries have often had an atrial switch procedure (Mustard or Senning operation) performed, which leaves the morphological right ventricle (RV) supporting the systemic circulation. RV failure and tricuspid regurgitation are common. Some patients may ultimately require cardiac transplantation. Sinus node dysfunction is increasingly common with longer follow-up, and some patients need pacemaker implantation. Atrial arrhythmias are frequent, and atrial flutter may be a marker for sudden death. Patients with an arterial switch procedure are also surviving to adulthood. Long-term problems include coronary stenoses, distortion of the pulmonary arteries, dilatation of the neoaortic root, and aortic regurgitation. Patients with congenitally corrected transposition have both atrioventricular and ventriculoarterial discordance and therefore also have a morphological RV and delicate tricuspid valve in the systemic circulation. Associated defects, such as abnormalities of the tricuspid valve, ventricular septal defect, and pulmonary stenosis, occur in the majority of patients. Heart block occurs with increasing age. Atrial arrhythmias occur frequently, and their occurrence should prompt a search for a hemodynamic problem. Progressive tricuspid regurgitation occurs with age and is associated with deterioration of RV function. Surgical treatment should be considered at the earliest sign of RV dilatation or dysfunction. All patients should be seen periodically in a center where expertise in the clinical evaluation, imaging, and hemodynamic assessment of adult congenital heart disease is available.
Recognition of pleural mesothelioma by mucin-1(950-958)/human leukocyte antigen A*0201-specific CD8+ T-cells
Authors: D. Roulois, V. Vignard, F. Gueugnon, N. Labarrière, M. Grégoire, J-F. Fonteneau
Journal: European Respiratory Journal (2011)

Recent clinical investigations have demonstrated that T-cell-based immunotherapy of malignant pleural mesothelioma (MPM) could represent an alternative to the other therapeutic strategies. However, its development suffers from the lack of identified tumour antigenic targets. Mucin (MUC)1, which is expressed and recognised by cytotoxic T-cells in numerous cancer types, has not been investigated as a potential immune target in MPM. Thus, the objective of this study was to analyse MUC1 expression by MPM cells and to determine whether this antigen can be the target of cytotoxic CD8+ T-cells (cytotoxic T-lymphocytes (CTLs)). We first evaluated the expression and glycosylation of MUC1 by MPM cell lines using different MUC1-specific monoclonal antibodies. We then obtained a CTL clone specific for a MUC1 peptide (residues 950–958) presented by human leukocyte antigen (HLA)-A*0201 and studied its interferon-γ and cytotoxic response to MPM cell lines. We found that all MPM cell lines expressed MUC1 protein at the cell surface with different glycosylation profiles. We also observed that HLA-A*0201+ MPM cell lines are recognised and lysed by a HLA-A*0201/MUC1(950–958)-specific CTL clone independently of the MUC1 glycosylation profile. Thus, MUC1 expression and antigen presentation by MPM cells may represent an attractive target for immunotherapeutic treatment of MPM despite its hyperglycosylated profile.
High molecular weight proteins purified from cardiac junctional sarcoplasmic reticulum vesicles are ryanodine-sensitive calcium channels.
Authors: D P Rardon, D C Cefali, R D Mitchell, S M Seiler, L R Jones
Journal: Circulation Research (1989)

The cardiac high molecular weight proteins/ryanodine receptors were purified to homogeneity from junctional sarcoplasmic reticulum membranes and shown to exhibit large conductance calcium channel activity. High molecular weight proteins were solubilized from junctional sarcoplasmic reticulum in zwitterionic detergent and purified by size-exclusion chromatography followed by sucrose density gradient centrifugation. The purified proteins exhibited an apparent Mr = 400,000-350,000, and bound [3H]ryanodine with a Kd of 4.6 nM and a Bmax of 140-280 pmol/mg protein. High molecular weight proteins demonstrated divalent cation channel activity after incorporation into planar lipid bilayers. Two channel types were identified. Large conductance channels had a slope conductance of 96 +/- 13 pS and a Erev of 42 +/- 9 mV (n = 5); small conductance channels had a slope conductance of 5.5 +/- 1 pS [1.0 microM cis CaCl2; 50 mM trans Ba(OH)2]. Reducing cis calcium from 1 microM to 1 nM reduced the large conductance channel open time from 7 +/- 1% to 0.1% (holding potential, -100 mV). Adding ATP (1 mM) to the cis chamber increased channel open time from 6 +/- 1% to 52 +/- 4% (holding potential, -100 mV); 10 nM ryanodine increased and 100 microM ryanodine decreased percent of open time of the 96 pS channel, without altering unitary channel conductance. The large conductance channel was similar to the calcium release channel detected in native canine cardiac junctional sarcoplasmic reticulum vesicles. Our data suggest that the ryanodine receptor, the calcium-release channel, and the high molecular weight proteins are all identical proteins containing allosteric regulatory sites for calcium, ATP, and ryanodine.
The interaction between HLA SE alleles and smoking and its contribution to autoimmunity against several citrullinated antigens
Authors: A. Willemze, D. van der Woude, W. G. Alemayehu, E. W. N. Levarht, G. Stoeken-Rijsbergen, W. Verduyn, R. R. P. de Vries, J. Houwing, T. W. J. Huizinga, L. A. Trouw, R. E. M. Toes
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> Recent data suggest that a gene-environment interaction exists between smoking and the HLA SE alleles in shaping the autoimmune reaction towards specific citrullinated antigens. Here, we determined the effects of HLA SE alleles and TE (tobacco exposure) on the immune response against various citrullinated antigens. These associations were analysed in the anticitrullinated peptide antibody (ACPA) - positive stratum to control for the possibility that found associations are explained by the known interaction between HLA SE alleles and TE on the ACPA status. <h3>Methods</h3> The reactivity of 661 RA patients against several citrullinated antigens from vimentin, fibrinogen, enolase and myelin basic protein was determined by ELISA. The effects of the HLA SE alleles and TE were assessed by logistic regression analysis. Biologic interaction was analysed by investigating if the effects of the risk factors combined exhibited departure from additivity. <h3>Results</h3> A significant interaction between TE and HLA SE alleles appeared present for the presence of ACPA as reported previously. When these interaction effects were studied for several ACPA ‘fine-specificities’ significant interactions were noted for several citrullinated peptides. However these interactions were not present after stratification for ACPA status, indicating that the interaction between TE and HLA SE alleles does not influence autoimmunity towards specific citrullinated antigens, but rather to ACPA development. <h3>Conclusion</h3> Our data indicate that the gene-environment interaction between HLA SE alleles and smoking does not shape the reactivity of the ACPA response.
Stroke and Neurovascular Protection
Authors: Gregory J. del Zoppo
Journal: New England Journal of Medicine (2006)

Neurons are extremely sensitive cells, whose function, like that of all cells, can be influenced by changes in their environment. Using pumps to regulate the internal and external electrolyte milieu, neurons keep toxic calcium ions outside the cell but allow the cell membrane to transmit signals electrically. If changes in the environment damage the membranes or if the energy-driven pumps fail, calcium ions can enter the neuron and permanently disable it. Local oxygen deprivation, such as that which occurs during ischemic stroke, can lead rapidly to transient or permanent injury of neurons by affecting the cells' energy requirements, pump function, . . .
Survival Analysis of Cancer Risk Reduction Strategies for <i>BRCA1/2</i> Mutation Carriers
Authors: Allison W. Kurian, Bronislava M. Sigal, Sylvia K. Plevritis
Journal: Journal of Clinical Oncology (2009)

Purpose Women with BRCA1/2 mutations inherit high risks of breast and ovarian cancer; options to reduce cancer mortality include prophylactic surgery or breast screening, but their efficacy has never been empirically compared. We used decision analysis to simulate risk-reducing strategies in BRCA1/2 mutation carriers and to compare resulting survival probability and causes of death. Methods We developed a Monte Carlo model of breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years, prophylactic mastectomy (PM) at various ages, and/or prophylactic oophorectomy (PO) at ages 40 or 50 years in 25-year-old BRCA1/2 mutation carriers. Results With no intervention, survival probability by age 70 is 53% for BRCA1 and 71% for BRCA2 mutation carriers. The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. The combination of PM and PO at age 40 improves survival more than any single intervention, yielding 24% survival gain for BRCA1 and 11% for BRCA2 mutation carriers. PM at age 25 instead of age 40 offers minimal incremental benefit (1% to 2%); substituting screening for PM yields a similarly minimal decrement in survival (2% to 3%). Conclusion Although PM at age 25 plus PO at age 40 years maximizes survival probability, substituting mammography plus MRI screening for PM seems to offer comparable survival. These results may guide women with BRCA1/2 mutations in their choices between prophylactic surgery and breast screening.