tbuckley/cabot-search huggingface dataset:
Toll-like receptor 7 function is reduced in adolescents with asthma
Authors: M. Roponen, S. T. Yerkovich, E. Hollams, P. D. Sly, P. G. Holt, J. W. Upham
Journal: European Respiratory Journal (2009)

Anti-viral innate immune responses may be impaired in asthma, although the mechanisms are not well understood. Toll-like receptors (TLRs) 7 and 3 are particularly relevant for initiating responses to common respiratory viruses, as they recognise single-stranded viral RNA and double-stranded viral RNA, respectively. The aim of the present study was to investigate TLR7 and TLR3 function in 14-yr-old adolescents with asthma. Blood mononuclear cells obtained from 17 atopic asthmatics, 29 atopic, non-asthmatics and 21 healthy, non-atopic individuals, were stimulated with the TLR7 agonist imiquimod and the TLR3 agonist poly I:C. Expression of anti-viral molecules was measured by real-time PCR. Concentrations of interferon-gamma-inducible cytokine protein (IP)-10 and interleukin (IL)-6 were measured by ELISA. TLR7-induced myxovirus resistance protein A and 2'5' oligoadenylate synthetase mRNA expression and protein levels of IP-10 were significantly lower in asthma subjects compared with healthy subjects (p = 0.041, p = 0.003 and p = 0.001 respectively). There was a significant negative correlation between total serum immunoglobulin E and IP-10 following TLR7 stimulation. However, TLR3-induced responses did not vary with asthma or atopy. IL-10 mRNA and IL-6 protein synthesis were similar in asthmatic and control subjects. In conclusion, TLR7 function is reduced in adolescents with asthma and this may contribute to susceptibility to respiratory viral infections.
Effect of Changes in Heart Rate on Left Ventricular Performance in Conscious Dogs
Authors: MARK I. M. NOBLE, JANE WYLER, ERIC N. C. MILNE, DIANA TRENCHARD, ABRAHAM GUZ
Journal: Circulation Research (1969)

An increase in heart rate produced in 12 conscious dogs by right atrial pacing resulted in a fall of end-diastolic volume, stroke volume, stroke work and end-diastolic pressure. Stroke power and the maximum rate of increase of left ventricular pressure (LV dP/dt max) were affected only slightly. Sudden large changes of rate produced transient changes in LV dP/dt max typical of the positive and negative inotropic effects of activation, but steady-state LV dP/dt max was not affected; these effects persisted after autonomic blockade with propranolol and atropine. Postural changes produced no change in LV dP/dt max even after autonomic blockade. We conclude that in this preparation, the interval-strength relationship has a plateau at the physiologic range of heart rate, i.e., myocardial contractility is unaffected by change in heart rate over the range 90 to 190 beats/min.
Phase II study of an optimized 5-fluorouracil-oxaliplatin strategy (OPTIMOX2) with celecoxib in metastatic colorectal cancer: a GERCOR study
Authors: T. André, C. Tournigand, L. Mineur, R. Fellague-Chebra, M. Flesch, M. Mabro, M. Hebbar, S. Postel Vinay, F.C. Bidard, C. Louvet, A. de Gramont
Journal: Annals of Oncology (2006)
Effect of L-arginine on renal blood flow in normal subjects and patients with hypoxic chronic obstructive pulmonary disease.
Authors: T. Q. Howes, S. E. Keilty, V. L. Maskrey, C. R. Deane, S. V. Baudouin, J. Moxham
Journal: Thorax (1996)

BACKGROUND: L-arginine is the precursor of endothelium derived nitric oxide (NO) and increasing the available substrate may increase the production of NO. This has been shown by local infusion in peripheral vascular beds but there are few studies of the effects during systemic infusion. Renal vasoconstriction is known to be important in the pathogenesis of cor pulmonale in patients with hypoxic chronic obstructive pulmonary disease (COPD). The effects of a systemic infusion of L-arginine on renal and aortic haemodynamics were therefore investigated in normal subjects and in patients with hypoxic COPD. METHODS: Ten normal volunteers were recruited from the research staff of King9s College Hospital Six patients with COPD and hypoxia (arterial oxygen tension (PaO2) &lt; 8.5 kPa) were recruited from the thoracic medicine outpatient clinic at King9s College Hospital and five age and sex matched normal subjects were recruited from a group of normal subjects recruited from the database of the Department of Health Care for the Elderly as volunteers for medical research. There was no history of renal, cardiac, or hepatic disease. Baseline values of time averaged mean of the maximum instantaneous velocity (Tamx) and maximum velocity (Vmax) of blood flow in intrarenal arteries were obtained using colour flow Doppler ultrasound. Using the same technique, Vmax was obtained from the abdominal aorta just distal to the xiphisternum before and after infusion of L-arginine via a large peripheral vein (20 g in 100 ml sterile water over 30 minutes). RESULTS: In normal subjects L-arginine increased blood velocity in the intrarenal vessels from a mean of 0.22 m/s to 0.26 m/s, an increase of 19.8%. There was no effect on arterial blood pressure, heart rate, or aortic blood velocity. L-arginine had no effect on intrarenal or aortic blood velocity in patients with hypoxic COPD. In age matched controls L-arginine increased blood velocity in the intrarenal vessels from a mean of 0.20 m/s to 0.26 m/s, an increase of 36.8%. There was no effect on arterial blood pressure, heart rate, or aortic blood velocity. CONCLUSIONS: L-arginine, at the doses administered, increased renal blood flow, as assessed by renal arterial velocity. This effect was not seen in patients with hypoxic COPD but was present in age matched controls. This suggests that the abnormal renal vascular control seen in hypoxic patients with COPD may reflect a disturbance of the L-arginine/nitric oxide pathway.
Influence of Letrozole and Anastrozole on Total Body Aromatization and Plasma Estrogen Levels in Postmenopausal Breast Cancer Patients Evaluated in a Randomized, Cross-Over Study
Authors: Jürgen Geisler, Ben Haynes, Gun Anker, Mitch Dowsett, Per Eystein Lønning
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To compare the effects of the two novel, potent, nonsteroidal aromatase inhibitors anastrozole and letrozole on total-body aromatization and plasma estrogen levels. PATIENTS AND METHODS: Twelve postmenopausal women with estrogen receptor–positive, metastatic breast cancer were treated with anastrozole 1 mg orally (PO) and letrozole 2.5 mg PO once daily, each given for a time interval of 6 weeks in a randomized sequence. Total-body aromatization was determined before treatment and at the end of each treatment period using a dual-label isotopic technique involving isolation of the metabolites with high-performance liquid chromatography. Plasma levels of estrone (E 1 ), estradiol (E 2 ), and estrone sulfate (E 1 S) were determined in samples obtained before each injection using highly sensitive radioimmunoassays. RESULTS: Pretreatment aromatase levels ranged from 1.68% to 4.27%. On-treatment levels of aromatase were detectable in 11 of 12 patients during treatment with anastrozole (mean percentage inhibition in the whole group, 97.3%) but in none of the 12 patients during treatment with letrozole (&gt; 99.1% suppression in all patients; Wilcoxon, P = .0022, comparing the two drug regimens). Treatment with anastrozole suppressed plasma levels of E 1 , E 2 , and E 1 S by a mean of 81.0%, 84.9%, and 93.5%, respectrively, whereas treatment with letrozole caused a corresponding decrease of 84.3%, 87.8% and 98.0%, respectively. The suppression of E 1 and E 1 S was found to be significantly better during treatment with letrozole compared with anastrozole (P = .019 and .0037, respectively). CONCLUSION: This study revealed letrozole (2.5 mg once daily) to be a more potent suppressor of total-body aromatization and plasma estrogen levels compared with anastrozole (1 mg once daily) in postmenopausal women with metastatic breast cancer.
ANTIGENIC PROPERTIES OF MURINE SARCOMA VIRUS-TRANSFORMED BALB/3T3 NONPRODUCER CELLS
Authors: John R. Stephenson, Stuart A. Aaronson
Journal: The Journal of Experimental Medicine (1972)

The isolation of clonal lines of murine sarcoma virus-transformed, non-producer BALB/3T3 cells has provided a model system for determining whether RNA tumor virus-transformed cells possess virus-specific transplantation antigens. MSV nonproducer cells (K-234) were clonally derived from an inbred mouse cell line, BALB/3T3. A parallel virus-producing cell line was obtained by infection of the MSV nonproducer cells with Rauscher leukemia virus. K-234 was much more tumorigenic than K-234(R). Preimmunization of syngeneic mice with either K-234(R) or with UV-inactivated Rauscher leukemia virus induced transplantation resistance to subsequent challenge with K-234(R), but not with K-234. In contrast, mice preimmunized with nonproducer cells were not made resistant to subsequent challenge with the homologous cells. Antisera prepared from mice immunized with K-234(R) were specifically cytotoxic and positive by fluorescent antibody staining for K-234(R) target cells, but not to either BALB/3T3 or K-234. The results show that MSV nonproducer cells lack detectable transplantation antigens and suggest that the transplantation resistance to the producing cells is attributable to maturing virus at the cell surface.
Effects of short chain fatty acids on gut morphology and function.
Authors: W Scheppach
Journal: Gut (1994)

Short chain fatty acids (SCFAs) are the products of colonic bacterial degradation of unabsorbed starch and non-starch polysaccharide (fibre). They are important anions in the colonic lumen, affecting both colonocyte morphology and function. The three main acids (acetate, propionate, and butyrate) stimulate colonic sodium and fluid absorption and exert proliferative effects on the colonocyte. Experimental animal studies have shown that they promote adaptive responses to small intestinal resection and colonic anastomosis. Acetate increases colonic blood flow and enhances ileal motility. Butyrate has been shown to be the preferred energy substrate for the colonocyte and to be a potent differentiating agent in cell culture. Butyrate may also have a role in preventing certain types of colitis. A diet low in resistant starch and fibre, which will result in a low production of SCFAs in the colon, may explain the high occurrence of colonic disorders seen in the Western civilization.
Use of peak flow variability and methacholine responsiveness in predicting changes from pre-test diagnosis of asthma
Authors: K Parameswaran, J Belda, MR Sears
Journal: European Respiratory Journal (1999)

Asthma is usually diagnosed clinically. This study investigated how methacholine challenge and peak expiratory flow monitoring influenced change from a pretest clinical diagnosis. Records of 132 patients referred with respiratory symptoms, who subsequently had reliable measurements of both airway responsiveness (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1 (PC20)) and peak expiratory flow variability (PEFV) were reviewed. Initial and final diagnoses for each patient were classified as: a) definite asthma; b) possible asthma; and c) definitely not asthma. The predictive value of PEFV and PC20 regarding overall change from pre- to post-test diagnosis, change from initial diagnosis of possible or definitely not asthma, and change from initial diagnosis of definite asthma, were tested by multiple logistic regression analysis. Odds ratios for PC20 were expressed per doubling dose, and for PEFV per 5% variability. Clinical diagnosis of definite asthma and definitely not asthma were confirmed in 70% and 79% respectively. PC20, but not PEFV, predicted an overall change between pre- and post-test diagnosis. Both PC20 and PEFV independently predicted change to definite asthma. PEFV and interaction between PC20 and PEFV predicted a change in those whose initial diagnosis was definite asthma. Although both measurements showed a significant correlation, there was poor agreement between positive tests. Both peak expiratory flow variability and provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second influence diagnostic decision-making in patients with a high pre-test probability of asthma.
Allergic reactions to $beta;-lactams ? in vitro and in vivo diagnosis*1
Authors: A.Lopes Pregal, M.C. Santos, A. Spínola Santos, S.Lopes Silva, M.Branco Ferreira, E. Pedro, G. Palma-Carlos, M.L. Palma-Carlos, A.G. Palma-Carlos, M.Pereira Barbosa
Journal: Journal of Allergy and Clinical Immunology (2004)
Plasma Matrix Metalloproteinase-9 as a Marker of Blood Stasis in Varicose Veins
Authors: Marie-Paule Jacob, Michèle Cazaubon, Anthony Scemama, Dominique Prié, Françoise Blanchet, Marie-Claude Guillin, Jean-Baptiste Michel
Journal: Circulation (2002)

Background — Possible intermediate circulating markers linking blood stasis to vein remodeling were explored in patients with varicose veins in the lower limbs. Methods and Results — Blood was sampled at rest (supine position) and after a stasis of 30 minutes both in the varicose vein (limbs hanging down) and in the brachial vein (arm hanging down) as a paired control. Several endothelial and leukocyte markers were measured in plasma with the use of ELISA kits. Angiotensin-converting enzyme activity was determined by use of a specific substrate. Matrix metalloproteinases (MMPs) 9 and 2 were evaluated with the use of gelatin zymography. No markers were significantly modified after 30 minutes of blood stasis in the brachial vein. After 30 minutes of blood stasis in the varicose vein, oxygen partial pressure decreased ( P &lt;0.01). Although thrombomodulin, von Willebrand factor, vascular endothelial growth factor, and MMP-2 were not modified in these conditions, the proteins released by proteolysis from the endothelial membrane intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and angiotensin-converting enzyme were increased ( P &lt;0.01). After blood stasis in varicose veins, the leukocyte markers lactoferrin, myeloperoxidase, and interleukin-8 were not modified, whereas L-selectin shed from leukocytes increased ( P &lt;0.05), and a major increase in pro-MMP-9, which is released from tertiary granules during polymorphonuclear activation, was observed ( P =0.0001). Conclusions — The marked increase in plasma pro-MMP-9 activity provides evidence of polymorphonuclear activation and granule release in the varicose vein in response to postural blood stasis. Similarly, detection in the plasma of membrane proteins shed from the endothelium or leukocytes provides evidence of pericellular proteolysis.
STRUCTURE, FUNCTION, AND DIETARY REGULATION OF Δ6, Δ5, AND Δ9 DESATURASES
Authors: Manabu T. Nakamura, Takayuki Y. Nara
Journal: Annual Review of Nutrition (2004)

Fatty acid desaturases introduce a double bond in a specific position of long-chain fatty acids, and are conserved across kingdoms. Degree of unsaturation of fatty acids affects physical properties of membrane phospholipids and stored triglycerides. In addition, metabolites of polyunsaturated fatty acids are used as signaling molecules in many organisms. Three desaturases, Delta9, Delta6, and Delta5, are present in humans. Delta-9 catalyzes synthesis of monounsaturated fatty acids. Oleic acid, a main product of Delta9 desaturase, is the major fatty acid in mammalian adipose triglycerides, and is also used for phospholipid and cholesteryl ester synthesis. Delta-6 and Delta5 desaturases are required for the synthesis of highly unsaturated fatty acids (HUFAs), which are mainly esterified into phospholipids and contribute to maintaining membrane fluidity. While HUFAs may be required for cold tolerance in plants and fish, the primary role of HUFAs in mammals is cell signaling. Arachidonic acid is required as substrates for eicosanoid synthesis, while docosahexaenoic acid is required in visual and neuronal functions. Desaturases in mammals are regulated at the transcriptional level. Reflecting overlapping functions, three desaturases share a common mechanism of a feedback regulation to maintain products in membrane phospholipids. At the same time, regulation of Delta9 desaturase differs from Delta6 and Delta5 desaturases because its products are incorporated into more diverse lipid groups. Combinations of multiple transcription factors achieve this sophisticated differential regulation.
PC-1 Amino Acid Variant Q121 Is Associated With a Lower Glomerular Filtration Rate in Type 2 Diabetic Patients With Abnormal Albumin Excretion Rates
Authors: Salvatore De Cosmo, Roberto Trevisan, Michele Dalla Vestra, Monica Vedovato, Alessandra Argiolas, Anna Solini, Alois Saller, Francesco Damone, Antonio Tiengo, Vincenzo Trischitta, Paola Fioretto
Journal: Diabetes Care (2003)

OBJECTIVE—To study the relationships between the PC-1 K121Q variant and diabetic nephropathy (DN) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 125 patients with type 2 diabetes and abnormal albumin excretion rate (AER) (range 20–5,416 μg/min) were followed up for 4 years with repeated measurements of glomerular filtration rate (GFR). Genomic DNA was extracted from all patients, and the PC-1 K121Q polymorphism was determined by the PCR AvaII restriction enzyme. A subset of 64 patients underwent a percutaneous kidney biopsy at baseline, and glomerular structure was analyzed by electron microscopic morphometric analysis. At baseline, age (56 ± 8 vs. 59 ± 7 years), BMI (28.3 ± 4.3 vs. 28.6 ± 3.7 kg/m2), known duration of type 2 diabetes (11.1 ± 7 vs. 11.9 ± 8 years), and HbA1c (8.6 ± 1.8 vs. 8.4 ± 1.7%) were similar in K121K (KK, n = 87, 73 men/14 women) and XQ (35 K121Q + 3 Q121Q, n = 38, 27 men/11 women) patients. Baseline GFR was 96 ± 28 ml · min−1 · 1.73 m−2 and was related (P = 0.01–0.001) to age, known diabetes duration, and systolic blood pressure. RESULTS—XQ patients had lower GFR (P &amp;lt; 0.05) than KK patients (88 ± 30 vs. 100 ± 26 ml · min−1 · 1.73 m−2); this difference persisted also after factoring in age and known diabetes duration. The rate of progression of DN was similar in KK and XQ patients: %ΔGFR was 4.1/year (median, range: 22.9–30.6) vs. 4.2/year (9.8–26.7). Morphometric parameters of diabetic glomerulopathy were similar in the two genotype groups. CONCLUSIONS—Among patients with type 2 diabetes with abnormal AER, those carrying the Q PC-1 genotype have more severe DN but not a faster GFR decline than KK patients, thus suggesting faster DN development since diabetes diagnosis in XQ patients.
School-based suicide prevention programmes: the SEYLE cluster-randomised, controlled trial
Authors: Danuta Wasserman, Christina W Hoven, Camilla Wasserman, Melanie Wall, Ruth Eisenberg, Gergö Hadlaczky, Ian Kelleher, Marco Sarchiapone, Alan Apter, Judit Balazs, Julio Bobes, Romuald Brunner, Paul Corcoran, Doina Cosman, Francis Guillemin, Christian Haring, Miriam Iosue, Michael Kaess, Jean-Pierre Kahn, Helen Keeley, George J Musa, Bogdan Nemes, Vita Postuvan, Pilar Saiz, Stella Reiter-Theil, Airi Varnik, Peeter Varnik, Vladimir Carli
Journal: The Lancet (2015)
Contamination of Probiotic Preparations With Milk Allergen Can Cause Anaphylaxis in Cow's Milk Allergic Patients
Authors: M. Morisset, T.T. Lee, C.M.N. Astier, D.A. Moneret-Vautrin, V. Cordebar, E. Beaudouin, F. Codreanu, B.E. Bihain, G. Kanny
Journal: Journal of Allergy and Clinical Immunology (2007)
Serum type III procollagen peptide in alcoholic liver disease and idiopathic hemochromatosis: Its relationship to hepatic fibrosis, activity of the disease and iron overload
Authors: Massimo Colombo, Giorgio Annoni, Maria Francesca Donato, Dario Conte, Dino Martines, Maria Grazia Zaramella, Paolo A. Bianchi, Alberto Piperno, Claudio Tiribelli
Journal: Hepatology (1985)

To assess the value of type III procollagen peptide (sPIIIP) as a marker of hepatic fibrosis, sera from 73 patients with alcohol-related liver disease and 30 patients with idiopathic hemochromatosis (IHC) were studied by a specific radioimmunoassay. sPIIIP was increased in 87% of 30 patients with cirrhosis, in 16% of 32 with steatofibrosis but in none of 11 with steatosis. There was a significant correlation with histologic hepatocellular necroinflammation (r = 0.42, p < 0.01), but not with hepatic fibrosis. sPIIP was increased in 33% of 30 patients with IHC, whether or not they had cirrhosis or fibrosis, and whatever the level of iron overload or the extent of the hepatic deterioration. IHC patients with increased levels of sPIIIP had a higher prevalence of superimposed hepatic damage than did those with normal procollagen levels (p < 0.05). Our findings, therefore, weaken the diagnostic value of sPIIIP as an index of connective tissue deposition in the liver, and suggest that, at least in alcohol-related liver disease and IHC, hepatocellular necroinflammation influences the results.
Peripheral Vascular Disease in Diabetes Mellitus and Its Relation to Cardiovascular Risk Factors: Screening with the Doppler Ultrasonic Technique
Authors: Hans U Janka, Eberhard Standl, Hellmut Mehnert
Journal: Diabetes Care (1980)

Data of 623 nonselected diabetic outpatients are presented who were screened for peripheral vascular disease (PVD) and for cardiovascular risk factors. PVD was diagnosed in 15.9% of the diabetic patients (14.4% women and 18.0% men). Nine percent of the patients had signs of marked mediasclerosis at the ankle level. Multivariate statistical analysis revealed that PVD was closely associated with systolic hypertension and also with the duration of diabetes, a relationship that was highly significant (P less than 0.001) for the peripheral type (below the knee) of PVD. Diabetic patients with arterial disease at the pelvic or femoral site exhibited a higher number of cardiovascular risk factors. In contrast, in patients with the peripheral type, significantly higher blood glucose values were found. Therefore, the quality of metabolic control may play an important part in the development of this form of diabetic macroangiopathy.
Acute effects of tobacco smoke on human airway dendritic cells in vivo
Authors: M. Lommatzsch, K. Bratke, T. Knappe, A. Bier, K. Dreschler, M. Kuepper, P. Stoll, P. Julius, J. C. Virchow
Journal: European Respiratory Journal (2009)

Airway dendritic cells (DCs) play a key role in smoke-related lung diseases; however, the acute effects of tobacco smoke on human airway DCs <i>in vivo</i> are unknown. A total of 16 smokers underwent bronchoalveolar lavage at two time-points: directly after a 4-h period of nonsmoking (no smoke exposure); and directly after a 4-h period during which eight cigarettes were smoked (acute smoke exposure). Using flow cytometry, myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), as well as function-associated surface molecules on mDCs, were analysed in bronchoalveolar lavage fluid (BALF) and in blood. The numbers of macrophages, lymphocytes, neutrophils, eosinophils and pDCs were unchanged in BALF following acute smoke exposure, as compared to no smoke exposure. In contrast, there was a strong increase in mDC number in BALF and a concomitant decrease in mDC number in blood following acute smoke exposure. In addition, acute smoke exposure led to an increase in the expression of the surface molecules blood dendritic cell antigen 1 and 4 and a decrease in the expression of the lung homing receptor, CC chemokine receptor 5, on mDCs in BALF. Acute tobacco smoke inhalation results in an immediate and selective recruitment of mDCs into human airways, which might reflect the very early reaction of the adaptive immune system to smoke exposure.