tbuckley/cabot-search huggingface dataset:
High ω-3 Fatty Acid Content in Alpine Cheese
Authors: Christa B. Hauswirth, Martin R.L. Scheeder, Jürg H. Beer
Journal: Circulation (2003)

Alpha-linolenic acid (ALA) may protect from cardiovascular disease. Because fresh alpine grass contains high amounts of ALA, we hypothesized that the levels of omega-3 fatty acids would concentrate to nutritional relevance in the cheese of milk from cows with alpine grass feeding compared with cheese from silage and concentrate feeding; the newly available cheese produced from cows fed with linseed supplementation should contain even higher ALA concentrations.Forty different cheeses were analyzed by gas chromatography for their fatty acid profile: (1) 12 from well-defined alpine regions around Gstaad, Switzerland; (2) 7 commercially available English cheddar cheeses; (3) 6 cheeses from cows fed with linseed supplementation; (4) 7 industrial-type Emmentals; and (5) 8 alpine cheeses with partial silage feeding. The alpine cheese contained 4 times more linolenic acid (C18:3omega-3) compared with cheddar, more total omega-3 fatty acids, and showed a significantly lower n-6:omega-3 ratio. Conjugated linoleic acid (C18:2 c9/t11) was 3-fold higher, whereas the amount of palmitic acid was 20% lower. The Emmental reached 40% of the ALA content compared with alpine cheese, and surprisingly, cheese from linseed-supplemented cows contained only 49% of that of the alpine cheese (P<0.001 for each trait in the 5 cheese groups).Cheese made of milk from cows grazed on alpine pastures had a more favorable fatty acid profile than all other cheese types. Alpine cheese may be a relevant source of ALA and other cardioprotective fatty acids.
Long‐term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors
Authors: Carlo Gambacorti‐Passerini, Hagop M. Kantarjian, Dong‐Wook Kim, Hanna J. Khoury, Anna G. Turkina, Tim H. Brümmendorf, Ewa Matczak, Nathalie Bardy‐Bouxin, Mark Shapiro, Kathleen Turnbull, Eric Leip, Jorge E. Cortes
Journal: American Journal of Hematology (2015)

Long-term efficacy and safety of bosutinib (≥4 years follow-up from last enrolled patient) were evaluated in an ongoing phase 1/2 study in the advanced leukemia cohort with prior treatment failure (accelerated-phase [AP, n = 79] chronic myeloid leukemia [CML], blast-phase [BP, n = 64] CML, acute lymphoblastic leukemia [ALL, n = 24]). Fourteen AP, 2 BP, and 1 ALL patient remained on bosutinib at 4 years (vs. 38, 8, 1 at 1 year); median (range) treatment durations: 10.2 (0.1-88.6), 2.8 (0.03-55.9), 0.97 (0.3-89.2) months. Among AP and BP patients, 57% and 28% newly attained or maintained baseline overall hematologic response (OHR); 40% and 37% attained/maintained major cytogenetic response (MCyR) by 4 years (most by 12 months). In responders at 1 versus 4 years, Kaplan-Meier (KM) probabilities of maintaining OHR were 78% versus 49% (AP) and 28% versus 19% (BP); KM probabilities of maintaining MCyR were 65% versus 49% (AP) and 21% versus 21% (BP). Most common AEs (AP, BP) were gastrointestinal (96%; 83%), primarily diarrhea (85%; 64%), which was typically low grade (maximum grade 1/2: 81%; 59%) and transient; no patient discontinued due to diarrhea. Serious AEs occurred in 44 (56%) AP and 37 (58%) BP patients, most commonly pneumonia (n = 9) for AP and pyrexia (n = 6) for BP; 11 and 13 died within 30 days of last dose (2 considered bosutinib-related [AP] per investigator). Responses were durable in ∼50% AP responders at 4 years (∼25% BP patients responded at year 1, suggesting possible bridge-to-transplant role in BP patients); toxicity was manageable.
Which patients are prescribed inhaled anti-asthma drugs?
Authors: S J Roberts, D N Bateman
Journal: Thorax (1994)

BACKGROUND--Prescribing rates for inhaled anti-asthmatic drugs in the UK vary considerably from area to area and between individual practices. The objectives of this study were to determine the prevalence of patients prescribed inhaled steroids and beta agonist bronchodilators, the indications for these prescriptions, and to relate prescribing to the recorded levels of morbidity for specific respiratory disease. METHODS--Anonymised patient-specific prescription and diagnostic data were extracted from computerised general practice records for the 41 practices in the Northern region (total population 330,749) whose data had been validated for inclusion in a research databank. Patients were included if they were either prescribed an inhaled steroid or bronchodilator during a 12 month period, or had a recorded diagnosis of asthma, bronchitis or chronic obstructive pulmonary disease. Prescribing of inhalers per 1000 population was determined within age, sex, and diagnostic groups. Respiratory diagnosis rates within different patient groups were used to measure the underlying level of morbidity in the population. RESULTS--Inhaled anti-asthma drugs were prescribed for 5% of the study population. Prescribing prevalences peaked at ages 5-14 (steroids 40 per 1000 population; bronchodilators 68 per 1000) and at ages 65-74 (steroids 53 per 1000; bronchodilators 79 per 1000). Prescribing frequency for both drugs increased from two or three items per patient annually at age 0-14 to about six in the over 65 age group. Of the 39,424 respiratory patients 38% received inhalers and 7% only non-inhaler medication. Inhaler therapy was used in only 6% of patients with bronchitis, but in 66% of those with asthma, though the proportions varied with patient age and gender. Study practices differed in their overall levels of both inhaler prescribing and respiratory diagnosis, and had lower prescribing patterns of these drugs than other practices in the Northern region. CONCLUSIONS--Inhaled steroid and bronchodilator prescribing have age-related and gender-related prevalences. Treatment for respiratory diagnoses varies with patient age and gender, and with the diagnosis. Prescribing differences between practices are attributable to variation in both diagnostic rates for respiratory disease and therapeutic intervention patterns. For asthma patients study practices show consensus in approach, perhaps illustrating the value of clear guidelines for asthma prescribing.
Management of Vasovagal Syncope
Authors: C.T. Paul Krediet, Nynke van Dijk, Mark Linzer, Johannes J. van Lieshout, Wouter Wieling
Journal: Circulation (2002)

Posture-related vasovagal syncope is by far the most frequent cause of transient loss of consciousness, and present pharmacological and cardiac pacing treatment remains unsatisfactory. A simple maneuver to prevent or diminish vasovagal reactions would be beneficial.Twenty-one patients with recurrent syncope (age 17 to 74 years, 11 males) who were referred for routine tilt-table testing and had a positive test were included. They were instructed to perform leg crossing and muscle tensing for at least 30 seconds at the onset of a tilt table-provoked impending faint. Continuously measured blood pressure and heart rate at nadir and during the maneuver were compared. Ten months after the test, a telephone follow-up was performed. The physical counter-maneuver, performed in 20 of 21 subjects, increased blood pressure and heart rate. Systolic blood pressure rose from 65+/-13 to 106+/-16 mm Hg (mean+/-SD, P<0.001), and diastolic blood pressure rose from 43+/-9 to 65+/-10 mm Hg (P<0.001). During the maneuver, prodromal symptoms disappeared in all patients, and none lost consciousness. After terminating the maneuver, symptoms did not return in 5 subjects during the test. At follow-up, 13 of 20 patients reported that they applied the maneuver in daily life and benefited from it.Leg crossing combined with tensing muscles at the onset of prodromal symptoms can postpone and in some subjects prevent vasovagal syncope.
Chances of Renal Recovery for Dialysis-Dependent ANCA-Associated Glomerulonephritis
Authors: Robert A.F. de Lind van Wijngaarden, Herbert A. Hauer, Ron Wolterbeek, David R.W. Jayne, Gill Gaskin, Niels Rasmussen, Laure-Hélène Noël, Franco Ferrario, Rüdiger Waldherr, Jan A. Bruijn, Ingeborg M. Bajema, E. Christiaan Hagen
Journal: Journal of the American Society of Nephrology (2007)

In patients who have anti-neutrophil cytoplasm autoantibody (ANCA)-associated glomerulonephritis and are on dialysis at time of diagnosis, renal function is sometimes insufficiently restored by immunosuppressive treatment, which often coincides with potentially lethal adverse effects. This study investigated the clinical and histologic variables that determine the chances of dialysis independence, dialysis dependence, or death after 12 mo in these patients. Sixty-nine patients who had ANCA-associated glomerulonephritis and were dialysis dependent at diagnosis received uniform, standard immunosuppressive therapy plus either intravenous methylprednisolone or plasma exchange. Eleven clinical and histologic variables were assessed. Univariate and binary logistic regression analyses were performed. Predictive parameters were entered into a two-step binary logistic regression analysis to differentiate among the outcomes of dialysis independence, dialysis dependence, or death. The point at which the chance of therapy-related death exceeded the chance of dialysis independence was determined. The chance of recovery exceeded the chance of dying in most cases. Intravenous methylprednisolone as adjunctive therapy plus <18% normal glomeruli and severe tubular atrophy increased the chance of therapy-related death over the chance of dialysis independence. Plasma exchange treatment plus severe tubular atrophy and <2% normal glomeruli increased the chance of therapy-related death over that of dialysis independence. Even with ominous histologic findings, the chance of renal recovery exceeds the chance of therapy-related death when these patients are treated with plasma exchange as adjunctive therapy.
Endothelin Receptor Antagonists in Proteinuric Renal Disease
Authors: Eberhard Ritz, René Wenzel
Journal: Journal of the American Society of Nephrology (2010)

When Yanagisawa et al. 1 first identified endothelin (ET), a novel polypeptide vasoconstrictor for which numerous other functions were identified later,2 there was early widespread enthusiasm and great expectation for therapeutic opportunities. ET-1 is the most powerful vasoconstrictor in this peptide family; the ET system is complex with a converting enzyme and two receptors, ETA-R and ETB-R. The receptors offer an opportunity for selective blockade. ETA-R primarily mediates vasoconstriction and plays a role in the genesis of hypertension, states of endothelial dysfunction, insulin resistance, inflammation, and fibrosis. From a renal perspective, it is important to note that both ETA-R and ETB-R are found in the kidney, ETA-R in vessels and ETB-R mainly in the medulla3 but also in glomeruli.4 Of note, collecting duct ETB-R null mice develop elevated BP, pointing to a potential causal role in the genesis of hypertension.5 It was immediately perceived that such a multifunctional system might provide promising therapeutic targets, but early enthusiasm waned when renin-angiotensin system (RAS) blockade stole the show. But the slogan “they never come back” apparently is not true for drugs.

Today it is clear that RAS blockade with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in renal patients does not consistently reduce proteinuria, which is not only a powerful predictor but also a promoter of renal progression; this is true for the dosages recommended for hypertension control and even for supramaximal dosages.6 This shortcoming has triggered a search for novel interventions in addition to RAS blockade, such as mineralocorticoid receptor blockade,7 renin inhibitors,8 and …
Effects of haptoglobin polymorphisms and deficiency on susceptibility to inflammatory bowel disease and on severity of murine colitis
Authors: L Márquez, C Shen, I Cleynen, G De Hertogh, K Van Steen, K Machiels, C Perrier, V Ballet, S Organe, M Ferrante, L Henckaerts, G Galicia, P Rutgeerts, J L Ceuppens, S Vermeire
Journal: Gut (2011)

<h3>Background</h3> Haptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. Its gene (16q22) harbours a common polymorphism with two different alleles: <i>Hp1</i> and <i>Hp2</i>. Genotype <i>Hp22</i> has been shown to be over-represented in different immune diseases. Results in Crohn9s disease (CD) are contradictory. <h3>Aims</h3> To determine whether Hp plays a role in inflammatory bowel disease, both genetically and functionally. <h3>Methods</h3> 1061 patients with CD, 755 with ulcerative colitis (UC) and 152 with primary sclerosing cholangitis, as well as 452 healthy controls, were genotyped using touch-down PCR. To confirm association results, 464 CD trios and 151 UC trios were genotyped. Serum Hp concentrations were determined in 62 individuals of different genotype. Colitis was induced in mice with dextran sulphate sodium (DSS) and oxazolone (Oxa). Cytokine production was evaluated by mRNA quantification in colonic tissue and ELISA on supernatants of mesenteric lymph node cells. <h3>Results</h3> Prevalence of <i>Hp2</i> was higher in CD and UC than in controls. In the confirmatory cohorts, <i>Hp2</i> was over-transmitted to the affected offspring. Serum Hp concentrations were higher in individuals with genotypes <i>Hp11</i> and <i>Hp21</i> than in those with <i>Hp22</i> (1.38 vs 0.89 g/l). DSS- and Oxa-induced colitis were more severe in Hp-deficient mice than in control mice and accompanied by higher concentrations (although not statistically significantly different) of tissue mRNA for cytokines. Interleukin-17 production was significantly higher in the presence of Hp-deficient serum compared with wild-type serum. <h3>Conclusions</h3> The <i>Hp</i> gene may play a role in susceptibility to inflammatory bowel disease. Its implication in other immune diseases underscores the common pathways between these diseases. Experimental models of colitis showed that Hp has a protective role in inflammatory colitis, most likely by inhibiting the production of Th1 and Th17 cytokines.
Therapeutic Modulation of Urinary Bladder Function: Multiple Targets at Multiple Levels
Authors: Martin C. Michel
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Storage dysfunction of the urinary bladder, specifically overactive bladder syndrome, is a condition that occurs frequently in the general population. Historically, pathophysiological and treatment concepts related to overactive bladder have focused on smooth muscle cells. Although these are the central effector, numerous anatomic structures are involved in their regulation, including the urothelium, afferent and efferent nerves, and the central nervous system. Each of these structures involves receptors for—and the urothelium itself also releases—many mediators. Moreover, hypoperfusion, hypertrophy, and fibrosis can affect bladder function. Established treatments such as muscarinic antagonists, β-adrenoceptor agonists, and onabotulinumtoxinA each work in part through their effects on the urothelium and afferent nerves, as do α1-adrenoceptor antagonists in the treatment of voiding dysfunction associated with benign prostatic hyperplasia; however, none of these treatments are specifically targeted to the urothelium and afferent nerves. It remains to be explored whether future treatments that specifically act at one of these structures will provide a therapeutic advantage.
Growth and hypertrophy of the heart: towards an understanding of cardiac specific and inducible gene expression
Authors: M. v. Bilsen, K. R Chien
Journal: Cardiovascular Research (1993)

Journal Article Growth and hypertrophy of the heart: towards an understanding of cardiac specific and inducible gene expression Get access Marc van Bilsen, Marc van Bilsen Department of Physiology, Cardiovascular Research Institute Maastricht, University of Limburg, PO Box 6 16, 6200 MD Maastricht, The Netherlands: M van Bilsen; Department of Medicine, Center for Molecular Genetics, University of California San Diego, La Jolla, California, USA: K R Chien. Correspondence to Dr van Bilsen. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth R Chien Kenneth R Chien Department of Physiology, Cardiovascular Research Institute Maastricht, University of Limburg, PO Box 6 16, 6200 MD Maastricht, The Netherlands: M van Bilsen; Department of Medicine, Center for Molecular Genetics, University of California San Diego, La Jolla, California, USA: K R Chien. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 7, July 1993, Pages 1140–1149, https://doi.org/10.1093/cvr/27.7.1140 Published: 01 July 1993 Article history Received: 10 March 1993 Accepted: 21 March 1993 Published: 01 July 1993
The circadian clock and asthma
Authors: Hannah J Durrington, Stuart N Farrow, Andrew S Loudon, David W Ray
Journal: Thorax (2013)

It is characteristic of asthma that symptoms worsen overnight, particularly in the early hours of the morning. Nocturnal symptoms in asthma are common and are an important indicator for escalation of treatment. An extensive body of research has demonstrated that nocturnal symptoms of cough and dyspnea are accompanied by circadian variations in airway inflammation and physiologic variables, including airflow limitation and airways hyper-responsiveness. The molecular apparatus that underpins circadian variations, controlled by so called 'clock' genes, has recently been characterised. Clock genes control circadian rhythms both centrally, in the suprachiasmatic nucleus of the brain and peripherally, within every organ of the body. Here, we will discuss how clock genes regulate circadian rhythms. We will focus particularly on the peripheral lung clock and the peripheral immune clock and discuss how these might relate to both the pathogenesis and treatment of asthma.
Increased Cytokine Response of Rhinovirus-infected Airway Epithelial Cells in Chronic Obstructive Pulmonary Disease
Authors: Dina Schneider, Shyamala Ganesan, Adam T. Comstock, Catherine A. Meldrum, Raja Mahidhara, Adam M. Goldsmith, Jeffrey L. Curtis, Fernando J. Martinez, Marc B. Hershenson, Umadevi Sajjan
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Airway inflammation is a central feature of chronic obstructive pulmonary disease (COPD). COPD exacerbations are often triggered by rhinovirus (RV) infection.We hypothesized that airway epithelial cells from patients with COPD maintain a proinflammatory phenotype compared with control subjects, leading to greater RV responses.Cells were isolated from tracheobronchial tissues of 12 patients with COPD and 10 transplant donors. Eight patients with COPD had severe emphysema, three had mild to moderate emphysema, and one had no emphysema. All had moderate to severe airflow obstruction, and six met criteria for chronic bronchitis or had at least one exacerbation the previous year. Cells were grown at air-liquid interface and infected with RV serotype 39. Cytokine and IFN expression was measured by ELISA. Selected genes involved in inflammation, oxidative stress, and proteolysis were assessed by focused gene array and real-time polymerase chain reaction.Compared with control subjects, cells from patients with COPD demonstrated increased mRNA expression of genes involved in oxidative stress and the response to viral infection, including NOX1, DUOXA2, MMP12, ICAM1, DDX58/RIG-I, STAT1, and STAT2. COPD cells showed elevated baseline and RV-stimulated protein levels of IL-6, IL-8/CXCL8, and growth-related oncogene-alpha/CXCL1. COPD cells demonstrated increased viral titer and copy number after RV infection, despite increased IL-29/IFN-lambda1, IL-28A/IFN-lambda2, and IFN-inducible protein-10/CXCL10 protein levels. Finally, RV-infected COPD cultures showed increased mRNA expression of IL28A/IFNlambda2, IL29/IFNlambda1, IFIH1/MDA5, DDX58/RIG-I, DUOX1, DUOX2, IRF7, STAT1, and STAT2.Airway epithelial cells from patients with COPD show higher baseline levels of cytokine expression and increased susceptibility to RV infection, despite an increased IFN response.
cIAP2 Upregulated by E6 Oncoprotein via Epidermal Growth Factor Receptor/Phosphatidylinositol 3-Kinase/AKT Pathway Confers Resistance to Cisplatin in Human Papillomavirus 16/18–Infected Lung Cancer
Authors: Heng-Hsiung Wu, Jeng-Yuan Wu, Ya-Wen Cheng, Chi-Yi Chen, Ming-Ching Lee, Yih-Gang Goan, Huei Lee
Journal: Clinical Cancer Research (2010)

Inhibitors of antiapoptosis protein (IAP) have been implicated in the resistance to cisplatin. Therefore, verifying which pathway is involved in cIAP2 upregulation may be helpful in finding a feasible pathway inhibitor to increase the chemotherapeutic efficacy in human papillomavirus (HPV)-infected lung cancer.Specific inhibitors of different pathways were used to verify which pathway is involved in cIAP2 transcription. cIAP2 promoter fragments with various deletions and/or mutations were constructed by site-directed mutagenesis. cIAP2, epidermal growth factor receptor (EGFR), and phospho-AKT (p-AKT) expressions in 136 lung tumors were evaluated by immunohistochemistry.Our data show that two NF-κB (-209 to -200 and -146 to -137) and one CREB (cyclic AMP-responsive element binding protein; -52 to -42) binding sites in cIAP2 promoter region were responsible for cIAP2 upregulated by E6 in TL-1 cells. Moreover, CREB was phosphorylated by EGFR/phosphatidylinositol 3-kinase (PI3K) pathway. To test the involvement of cIAP2 on cisplatin resistance, IC(50) was lowered to 8.6 μmol/L in TL-1 cells with cIAP2 short hairpin RNA (shRNA) transfection and compared with 39.7 μmol/L in TL-1 cells with nonspecific shRNA. Pretreatment with EGFR or PI3K inhibitor in TL-1 cells diminished the resistance to cisplatin. Among the tumor groups, cIAP2 expression correlated significantly with HPV16/18 E6, EGFR, and p-AKT. We followed up 46 of 136 patients who had tumor recurrence and/or metastasis and underwent chemotherapy. Tumors with cIAP2-positive immunostaining were associated with a poorer tumor response to chemotherapy compared with those with negative immunostaining.cIAP2 upregulated by E6 via EGFR/PI3K/AKT cascades may contribute to cisplatin resistance, revealing that the EGFR or PI3K inhibitor combined with cisplatin may improve the chemotherapeutic efficacy in HPV-infected lung cancer.
Lack of Correlation Between Gross Chromosome Abnormalities and Carcinogenesis With 7,12-Dimethylbenz[α]anthracene2
Authors: P. O. Ottonen, J. K. Ball
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Lack of Correlation Between Gross Chromosome Abnormalities and Carcinogenesis With 7,12-Dimethylbenz[α]anthracene Get access P. O. Ottonen, P. O. Ottonen Cancer Research Laboratory, University of Western Ontario, London, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar J. K. Ball J. K. Ball Cancer Research Laboratory, University of Western Ontario, London, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 2, February 1973, Pages 497–501, https://doi.org/10.1093/jnci/50.2.497 Published: 01 February 1973 Article history Received: 18 August 1972 Accepted: 11 October 1972 Published: 01 February 1973