tbuckley/cabot-search huggingface dataset:
Toll-like Receptor Ligands Energize Peptide Vaccines through Multiple Paths
Authors: Esteban Celis
Journal: Cancer Research (2007)

Abstract The potential of vaccines for cancer therapy or prevention has yet to be realized. Recently, we showed that using an immunologic adjuvant composed of a Toll-like receptor (TLR) ligand can increase the production of antitumor CTLs produced by a peptide vaccine in a mouse model of breast cancer. By increasing the cross talk between the innate and adaptive immune systems, TLR ligands can drive expansion and memory of CTLs that can destroy cancer cells. [Cancer Res 2007;67(17):7945–7]
Environmental assessment and exposure reduction of cockroaches: A practice parameter
Authors: Jay Portnoy, Ginger L. Chew, Wanda Phipatanakul, P. Brock Williams, Carl Grimes, Kevin Kennedy, Elizabeth C. Matsui, J. David Miller, David Bernstein, Joann Blessing-Moore, Linda Cox, David Khan, David Lang, Richard Nicklas, John Oppenheimer, Christopher Randolph, Diane Schuller, Sheldon Spector, Stephen A. Tilles, Dana Wallace, James Seltzer, James Sublett
Journal: Journal of Allergy and Clinical Immunology (2013)
Tight junction properties of the immortalized human bronchial epithelial cell lines Calu‐3 and 16HBE14o‐
Authors: H. Wan, H.L. Winton, C. Soeller, G.a Stewart, P.j Thompson, D.c Gruenert, M.B. Cannell, D.r Garrod, C. Robinson
Journal: European Respiratory Journal (2000)

Tight junctions (TJs) make a vital contribution to the barrier properties of the airway lining. Opening of TJs, or their frank cleavage, is suspected as a pathophysiological event in the lung, but research into the cellular and molecular mechanisms involved has been impeded by technical limitations of available experimental models. The authors have compared the properties of two epithelial cell lines derived from bronchial epithelium to explore whether these cell lines could constitute appropriate tools for the study of TJ regulation in bronchial epithelium. Investigations of TJs in 16HBE14o- cells and Calu-3 cells were made by fluorescent antibody labelling in conjunction with wide-field, confocal or 2-photon molecular excitation microscopy (2PMEM). The presence of TJ proteins was confirmed by immunoblotting and functional properties of the monolayers were studied by measurements of transepithelial electrical resistance and mannitol permeability. Cells of both lines formed confluent monolayers in which the cells expressed the TJ proteins occludin and ZO-1 in continuous circumferential patterns suggestive of functional TJs. This interpretation was supported by the development of transepithelial electrical resistances and of low paracellular permeability to solutes. Within the limits of resolution offered by 2PMEM, occludin and ZO-1 appeared to colocalize at TJs. These studies suggest that the 16HBE14o- cells and Calu-3 cell lines are potentially useful in vitro models to study how tight junction opening or cleavage changes the functional barrier properties of bronchial epithelium.
Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies
Authors: H Kulaksiz
Journal: Gut (2002)

Background and aims: Recently, novel somatostatin receptor (sstr) subtype specific ligand analogues have been developed for medical treatment of neuroendocrine tumours expressing different sstrs (sstr1–5). At present, individual expression patterns of sstr subtypes are based on methods such as in situ hybridisation and polymerase chain reaction at the transcriptional level. Therefore, we generated subtype specific antibodies against sstr1, 2A, 3, and 5 and analysed their presence, cellular localisation, distribution, and expression pattern in 33 gastrinomas, 36 insulinomas, and 35 tumours associated with a carcinoid syndrome by immunohistochemistry at the translational level. Methods: Western blotting experiments were performed in the normal human pancreas used as a reference organ and in tumour tissues; at the cellular level, sstrs were localised by immunohistochemistry in tissue paraffin sections. Results: In western blot analyses, the antibodies identified the respective receptors in their correct molecular range in extracts of the pancreas and neuroendocrine tumours. Using immunohistochemistry and immunofluorescence, the antibodies specifically detected the receptors in islet cells of the normal pancreas. Immunohistochemistry in the tumours revealed that all investigated sstr subtypes were highly expressed in the different tumour types. The frequency and expression pattern of the individual sstr subtypes varied considerably not only between the different tumour types but also in each patient. Conclusions: We conclude that immunohistochemistry with subtype specific antibodies can be used in clinical routine work to analyse sstr expression patterns for each patient before treatment and to facilitate well directed individual medical therapy by administering subtype specific somatostatin analogues.
The expression regulation of the HSPA1B gene in patients with myositis is not dependent on the presence of HLA-DRB1*03 risk allele
Authors: M. Remakova, M. Skoda, M. Faustova, H. Mann, O. Krystufkova, J. Vencovsky, P. Novota
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Genes within the major histocompatibility complex (MHC) region has a strong genetic relevance in autoimmunity development. The involvement of the class I and class II genes, as well as class III (non-Class I/II MHC) genes has been proposed. For the myositis development, the HLA-DRB1*03 is a known risk factor in Caucasian population. However, there are another genes appearing to be significant players in the ethiology of myositis located near the HLA-DRB1 locus. In the present study the authors have focused on one of these risk factors – the regulation of MHC-linked inducible <i>HSP70</i> genes expression and their relation to the known immunogenetic risk factor located within the MHC (HLA-DRB1*03). <h3>Materials and methods</h3> The authors have investigated the gene specific <i>HSP70</i> expression in 20 patients with dermatopolymyositis and 15 healthy people matching in age as control samples. Expression levels of the two inducible <i>HSP70</i> genes (<i>HSPA1A</i>, <i>HSPA1B</i>) were analysed both in patients and controls. Both of the groups were additionally genotyped for HLA-DRB1 locus. Myositis-specific and associated autoantibodies were also identified in patients. <h3>Results</h3> The expression of both, the <i>HSPA1A</i> and <i>HSPA1B</i> genes was significantly upregulated (p&lt;0.001; p&lt;0.05) in patients suffering from myositis when compared to controls. The expression regulation of the <i>HSPA1A</i> was found to be associated with the presence of the HLA-DRB1*03 risk allele in patients. However, this was not observed for the <i>HSPA1B</i> gene. In contrast, the authors found a positive correlation between the expression regulation of the <i>HSPA1B</i> gene and the presence of disease specific autoantibodies in myositis patients. Additionally, positive correlation between the presence of disease specific autoantibodies and the HLA-DRB1*03 risk allele was found. None of these observations were found in healthy controls. <h3>Conclusions</h3> The results suggest that the two MHC-linked inducible genes are differentially expressed in dependence on the autoantibody or HLA risk allele presence. The differential gene expression regulation shows that the <i>HSPA1B</i> is an – on HLA-DRB1 – independent molecular marker for myositis development.
Protein evolution in different cellular environments: cytochrome b in sharks and mammals.
Authors: A P Martin, S R Palumbi
Journal: Molecular Biology and Evolution (1993)

DNA sequences for the mitochondrial cytochrome b gene were determined for 13 species of sharks. Rates and patterns of amino acid replacement are compared for sharks and mammals. Absolute rates of cytochrome b evolution are six times slower in sharks than in mammals. Bivariate plots of the number of nonsynonymous and silent transversions are indistinguishable in the two groups, however, suggesting that the differences in amino acid replacement rates are due primarily to differences in DNA substitution rates. Patterns of amino acid replacement are also similar in the two groups. Conserved and variable regions occur in the same parts of the cytochrome b gene, and there is little evidence that the types of amino acid changes are significantly different between the groups. Similarity in the relative rates and patterns of protein change between the two groups prevails despite dramatic differences in the cellular environments of sharks and mammals. Poor penetrance of physiological differences through to rates of protein evolution provides support for the neutral theory and suggests that, for cytochrome b, patterns of evolution have been relatively constant throughout much of vertebrate history.
Asbestos induces doxorubicin resistance in MM98 mesothelioma cells via HIF-1 
Authors: C. Riganti, S. Doublier, E. Aldieri, S. Orecchia, P. G. Betta, E. Gazzano, D. Ghigo, A. Bosia
Journal: European Respiratory Journal (2008)

Human malignant mesothelioma (HMM), which is strongly related to asbestos exposure, exhibits high resistance to many anticancer drugs. Asbestos fibre deposition in the lung may cause hypoxia and iron chelation at the fibre surface. Hypoxia-inducible factor (HIF)-1α, which is upregulated by a decreased availability of oxygen and iron, controls the expression of membrane transporters, such as P-glycoprotein (Pgp), which actively extrude the anticancer drugs. The present study aimed to assess whether asbestos may play a role in the induction of doxorubicin resistance in HMM cells through the activation of HIF-1α and an increased expression of Pgp. After 24-h incubation with crocidolite asbestos or with the iron chelator dexrazoxane, or under hypoxia, HMM cells were tested for HIF-1α activation, Pgp expression, accumulation of doxorubicin and sensitivity to its toxic effect. Crocidolite, dexrazoxane and hypoxia caused HIF-1α activation, Pgp overexpression and increased resistance to doxorubicin accumulation and toxicity. These effects were prevented by the co-incubation with the cell-permeating iron salt ferric nitrilotriacetate, which caused an increase of intracellular iron bioavailability, measured as increased activity of the iron regulatory protein-1. Crocidolite, dexrazoxane and hypoxia induce doxorubicin resistance in human malignant mesothelioma cells by increasing hypoxia-inducible factor-1α activity, through an iron-sensitive mechanism.
Ryanodine Receptor Mutations Associated With Stress-Induced Ventricular Tachycardia Mediate Increased Calcium Release in Stimulated Cardiomyocytes
Authors: Christopher H. George, Gemma V. Higgs, F. Anthony Lai
Journal: Circulation Research (2003)

Ca2+ release from the sarcoplasmic reticulum mediated by the cardiac ryanodine receptor (RyR2) is a fundamental event in cardiac muscle contraction. RyR2 mutations suggested to cause defective Ca2+ channel function have recently been identified in catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular dysplasia (ARVD) affected individuals. We report expression of three CPVT-linked human RyR2 (hRyR2) mutations (S2246L, N4104K, and R4497C) in HL-1 cardiomyocytes displaying correct targeting to the endoplasmic reticulum. N4104K also localized to the Golgi apparatus. Phenotypic characteristics including intracellular Ca2+ handling, proliferation, viability, RyR2:FKBP12.6 interaction, and beat rate in resting HL-1 cells expressing mutant hRyR2 were indistinguishable from wild-type (WT) hRyR2. However, Ca2+ release was augmented in cells expressing mutant hRyR2 after RyR activation (caffeine and 4-chloro-m-cresol) or beta-adrenergic stimulation (isoproterenol). RyR2:FKBP12.6 interaction remained intact after caffeine or 4-CMC activation, but was dramatically disrupted by isoproterenol or forskolin, an activator of adenylate cyclase. Isoproterenol and forskolin elevated cyclic-AMP to similar magnitudes in all cells and were associated with equivalent hyperphosphorylation of mutant and WT hRyR2. CPVT-linked mutations in hRyR2 did not alter resting cardiomyocyte phenotype but mediated augmented Ca2+ release on RyR-agonist or beta-AR stimulation. Furthermore, equivalent interaction between mutant and WT hRyR2 and FKBP12.6 was demonstrated.
Yes to NO: the first studies on exhaled nitric oxide-driven asthma treatment
Authors: J. C. de Jongste
Journal: European Respiratory Journal (2005)

Recently, the first long-term studies examining the use of fractional exhaled nitric oxide (FeNO) to titrate steroid treatment in asthma were published 1, 2. Treatment decisions in asthma have always been made on the basis of symptoms, with or without taking peak flow into account. It is well established that, within an asthma population, both symptoms and airway obstruction correlate poorly with the presence and severity of airway inflammation. A strategy where inflammometry identifies the patient with airway inflammation would potentially prevent over treatment and allow for titration towards the lowest effective dose of steroids. It may also alert for under treatment or noncompliance. The validity of the concept of inflammometry-driven asthma management was supported by two earlier studies, both showing an important reduction in asthma exacerbations as a result of treatment strategies aimed at the reduction of bronchial hyperresponsiveness or sputum eosinophilia, both proxies for airway inflammation in asthma 3, 4. These studies have had limited practical impact due to the invasive and time-consuming nature of both hyperresponsiveness testing and sputum induction, and because the hyperresponsiveness-driven strategy led to an increased dose of inhaled steroids.

The present introduction of FeNO measurements in clinical practise has been preceded by well over 1,000 published studies on FeNO in the past 15 yrs. These have established the genetic and molecular basis of nitric oxide (NO) generation and metabolism in the airways, the physiological and pathophysiological importance of NO in several respiratory diseases, and a number of confounding factors. FeNO can be measured within seconds with minimal discomfort and no risk to the patient. Routine methodology can be used in children from the age of ≥4–5 yrs. The results are highly reproducible and immediately available, and the test can be repeated easily and as often as needed. The American Thoracic Society …
Comparison of Citalopram, Perphenazine, and Placebo for the Acute Treatment of Psychosis and Behavioral Disturbances in Hospitalized, Demented Patients
Authors: Bruce G. Pollock, Benoit H. Mulsant, Jules Rosen, Robert A. Sweet, Sati Mazumdar, Ashok Bharucha, Robert Marin, N. J. Jacob, Kimberly A. Huber, Kari B. Kastango, Marci L. Chew
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Until recently, conventional antipsychotics were the standard pharmacotherapy for psychosis and behavioral disturbances associated with dementia. This double-blind, placebo-controlled study compared the acute efficacy of the selective serotonin reuptake inhibitor citalopram and the neuroleptic perphenazine with placebo for the treatment of psychosis and behavioral disturbances in nondepressed patients with dementia. METHOD: Eighty-five hospitalized patients with at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions) were randomly assigned to receive either citalopram, perphenazine, or placebo under double-blind conditions for up to 17 days. RESULTS: Patients treated with citalopram or perphenazine showed statistically significant improvement on several Neurobehavioral Rating Scale factor scores. Compared to those receiving placebo, only patients treated with citalopram showed significantly greater improvement in their total Neurobehavioral Rating Scale score as well as in the scores for the agitation/aggression and lability/tension factors. Side effect scores were similar among the three treatment groups. CONCLUSIONS: Citalopram was found to be more efficacious than placebo in the short-term hospital treatment of psychotic symptoms and behavioral disturbances in nondepressed, demented patients.
Expression of Podocyte-Associated Molecules in Acquired Human Kidney Diseases
Authors: Klaas Koop, Michael Eikmans, Hans J. Baelde, Hiroshi Kawachi, Emile de Heer, Leendert C. Paul, Jan A. Bruijn
Journal: Journal of the American Society of Nephrology (2003)

Proteinuria is a poorly understood feature of many acquired renal diseases. Recent studies concerning congenital nephrotic syndromes and findings in genetically modified mice have demonstrated that podocyte molecules make a pivotal contribution to the maintenance of the selective filtration barrier of the normal glomerulus. However, it is unclear what role podocyte molecules play in proteinuria of acquired renal diseases. This study investigated the mRNA and protein expression of several podocyte-associated molecules in acquired renal diseases. Forty-eight patients with various renal diseases were studied, including minimal change nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, lupus nephritis, and diabetic nephropathy, together with 13 kidneys with normal glomerular function. Protein levels of nephrin, podocin, CD2-associated protein, and podocalyxin were investigated using quantitative immunohistochemical assays. Real-time PCR was used to determine the mRNA levels of nephrin, podocin, and podoplanin in microdissected glomeruli. The obtained molecular data were related to electron microscopic ultrastructural changes, in particular foot process width, and to clinical parameters. In most acquired renal diseases, except in IgA nephropathy, a marked reduction was observed at the protein levels of nephrin, podocin, and podocalyxin, whereas an increase of the glomerular mRNA levels of nephrin, podocin, and podoplanin was found, compared with controls. The mean width of the podocyte foot processes was inversely correlated with the protein levels of nephrin (r = -0.443, P < 0.05), whereas it was positively correlated with podoplanin mRNA levels (r = 0.468, P < 0.05) and proteinuria (r = 0.585, P = 0.001). In the diseases studied, the decrease of slit diaphragm proteins was related to the effacement of foot processes and coincided with a rise of the levels of the corresponding mRNA transcripts. This suggests that the alterations in the expression of podocyte-associated molecules represent a compensatory reaction of the podocyte that results from damage associated with proteinuria.
Warfarin Interactions With Antibiotics in the Ambulatory Care Setting
Authors: Nathan P. Clark, Thomas Delate, Catherine S. Riggs, Daniel M. Witt, Elaine M. Hylek, David A. Garcia, Walter Ageno, Francesco Dentali, Mark A. Crowther
Journal: JAMA Internal Medicine (2014)

The effect of antibiotic coadministration on the international normalized ratio (INR) in a relatively stable, real-world warfarin population has not been adequately described. Case reports and studies of healthy volunteers do not account for the potential contribution of acute illness to INR variability.To compare the risk of excessive anticoagulation among patients with stable warfarin therapy purchasing an antibiotic (antibiotic group) with the risk in patients purchasing a warfarin refill (stable controls) and patients with upper respiratory tract infection but not receiving an antibiotic (sick controls).A retrospective, longitudinal cohort study evaluated patients receiving warfarin between January 1, 2005, and March 31, 2011, at Kaiser Permanente Colorado, an integrated health care delivery system. Continuous data were expressed as mean (SD) or median (interquartile range). Multivariable logistic regression analysis was used to identify factors independently associated with a follow-up INR of 5.0 or more. A total of 5857 (48.8%), 5579 (46.5%), and 570 (4.7%) patients were included in the antibiotic, stable control, and sick control groups, respectively. Mean age was 68.3 years, and atrial fibrillation was the most common (44.4%) indication for anticoagulation.Warfarin therapy with a medical visit for upper respiratory tract infection or coadministration of antibiotics.Primary outcomes were the proportion of patients experiencing a follow-up INR of 5.0 or more and change between the last INR measured before the index date and the follow-up INR.The proportion of patients experiencing an INR of 5.0 or more was 3.2%, 2.6%, and 1.2% for the antibiotic, sick, and stable groups, respectively (P < .001, antibiotic vs stable control group; P < .017, sick vs stable control group; P = .44, antibiotic vs sick control group). Cancer diagnosis, elevated baseline INR, and female sex predicted a follow-up INR of 5.0 or more. Among antibiotics, those interfering with warfarin metabolism posed the greatest risk for an INR of 5.0 or more.Acute upper respiratory tract infection increases the risk of excessive anticoagulation independent of antibiotic use. Antibiotics also increase the risk; however, most patients with previously stable warfarin therapy will not experience clinically relevant increases in INR following antibiotic exposure or acute upper respiratory tract infection.
Improving survival in pulmonary arterial hypertension
Authors: M. Humbert
Journal: European Respiratory Journal (2005)

More than 50 yrs ago, Dresdale et al . 1 reported a series of 39 patients with unexplained pulmonary hypertension and coined the term “primary pulmonary hypertension” to describe the condition, a term that has been revised to “idiopathic pulmonary arterial hypertension” in the most recent classification 2. Idiopathic pulmonary arterial hypertension is a disease of the small pulmonary arteries, which leads to a progressive increase in pulmonary vascular resistance, ultimately causing right ventricular failure and death 3, 4. Despite major advances in the understanding of the pathobiology of pulmonary arterial hypertension, none of the current therapeutic approaches achieves a cure for this devastating condition 5, 6.

Survival has been extensively studied in idiopathic pulmonary arterial hypertension 7. An American registry supported by the National Institute of Health (NIH) was begun in 1981 to collect data from 32 centres on patients diagnosed by uniform criteria as having so-called primary pulmonary hypertension 7, 8. Between July 1, 1981 and September 30, 1985, 194 patients were entered into the NIH registry, providing the first multicentre, detailed clinical and haemodynamic description of this disease 7, 8. This pioneer study allowed analysis of the survival and prognosis factors 7. As of August 1988, 106 of the 194 patients had died (mostly of right-heart failure and sudden death), emphasising the dismal prognosis of this condition 7. A total of 13 patients who had heart–lung transplant were followed only to the time of transplant, and 15 patients lost to follow-up were considered to be survivors, for purposes of the analysis 7. The estimated median survival from baseline catheterisation was 2.8 yrs, with estimated single-year survival rates at 1, 3, and 5 yrs of 68, 48, and 34%, respectively 7. Poor survival was associated with a …