tbuckley/cabot-search huggingface dataset:
IL-7–dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL
Authors: Joao T. Barata, Vassiliki A. Boussiotis, Jose A. Yunes, Adolfo A. Ferrando, Lisa A. Moreau, J. Pedro Veiga, Stephen E. Sallan, A. Thomas Look, Lee M. Nadler, Angelo A. Cardoso
Journal: Blood (2003)
Modulation of the biliary expression of arylalkylamine N-acetyltransferase alters the autocrine proliferative responses of cholangiocytes in rats
Authors: Anastasia Renzi, Sharon DeMorrow, Paolo Onori, Guido Carpino, Romina Mancinelli, Fanyin Meng, Julie Venter, Mellanie White, Antonio Franchitto, Heather Francis, Yuyan Han, Yoshiyuki Ueno, Giuseppina Dusio, Kendal J. Jensen, John J. Greene, Shannon Glaser, Eugenio Gaudio, Gianfranco Alpini
Journal: Hepatology (2012)

Secretin stimulates ductal secretion by interacting with secretin receptor (SR) activating cyclic adenosine 3′,5′-monophosphate/cystic fibrosis transmembrane conductance regulator/chloride bicarbonate anion exchanger 2 (cAMP⇒CFTR⇒Cl−/HCO Symbol AE2) signaling that is elevated by biliary hyperplasia. Cholangiocytes secrete several neuroendocrine factors regulating biliary functions by autocrine mechanisms. Melatonin inhibits biliary growth and secretin-stimulated choleresis in cholestatic bile-duct–ligated (BDL) rats by interaction with melatonin type 1 (MT1) receptor through down-regulation of cAMP-dependent signaling. No data exist regarding the role of melatonin synthesized locally by cholangiocytes in the autocrine regulation of biliary growth and function. In this study, we evaluated the (1) expression of arylalkylamine N-acetyltransferase (AANAT; the rate-limiting enzyme for melatonin synthesis from serotonin) in cholangiocytes and (2) effect of local modulation of biliary AANAT expression on the autocrine proliferative/secretory responses of cholangiocytes. In the liver, cholangiocytes (and, to a lesser extent, BDL hepatocytes) expressed AANAT. AANAT expression and melatonin secretion (1) increased in BDL, compared to normal rats and BDL rats treated with melatonin, and (2) decreased in normal and BDL rats treated with AANAT Vivo-Morpholino, compared to controls. The decrease in AANAT expression, and subsequent lower melatonin secretion by cholangiocytes, was associated with increased biliary proliferation and increased SR, CFTR, and Cl−/HCO Symbol AE2 expression. Overexpression of AANAT in cholangiocyte cell lines decreased the basal proliferative rate and expression of SR, CFTR, and Cl−/HCO Symbol AE2 and ablated secretin-stimulated biliary secretion in these cells. Conclusion : Local modulation of melatonin synthesis may be important for management of the balance between biliary proliferation/damage that is typical of cholangiopathies. (Hepatology 2013)
Component-resolved diagnosis of house dust mite allergy with a large repertoire of purified natural and recombinant allergens from the major species of mites worldwide
Authors: A.S.L. Tay, H.S. Shang, X.Z. Bi, K. Reginald, Y.F. Gao, S.T. Ong, A.C. Angus, W.L. Wang, K.T. Kuay, D.Y. Wang, A. Mari, F.T. Chew
Journal: Journal of Allergy and Clinical Immunology (2005)
THE EFFECT OF OCCULUSIVE AND SEMIUPERMEABLE DRESSINGS ON THE MITOTIC ACTRIVITY OF NORMAL AND WOUDED HUMAN EPIDERMIS
Authors: LOUIS B. FISHER, HOWARD I. MAIBACH
Journal: British Journal of Dermatology (1972)

Summary.— Occulusion has been shown to increase the rate of closure of superficial woulds. However, it has laos been shown to inhibit cell division both of psoriatic lesions and stripped skin. This work was undertaken to investigate further this appartent anomaly. Forur dressings—an occulsice, adhesive tape; the adhesive backing from thsi tape; a less occlusive adhesive tape; and an occulsive, non-adhesive film, were used to cover regions of normal and stripped skin for periods from 2 to 6 days. The results show a slight increase in mitotic rate and epidermal thickness of normal skin, under all dressings. These results are discussed and it is suggested that the less occlusive films might be of benefit in accelkerating the healing of wounds without adding the risk of infection seen under complete occulusion.
A comparison of methods for the rapid quantitation of unsaturated transcobalamin II and the r‐binding proteins
Authors: Francisco Fernandes‐Costa, Jack Metz
Journal: American Journal of Hematology (1979)

Methods for the rapid quantitation on unsaturated transcobalamin II (TC II) and R-binders in serum following separation of these binders using a) adsorption by uncoated charcoal, b) adsorption by Quso G32, c) precipitation with ammonium sulphate, and d) acidification of serum, have been compared with the standard gel filtration technique. In serum from healthy subjects and patients with elevated R-binders, the serum acidification and Quso methods yielded results in closest agreement with those obtained by gel filtration. When TC II was markedly elevated, the recommended concentration of Quso failed to remove all TC II from serum. Both the serum acidification and Quso methods are suitable for routine use, providing that with the latter method the concentration of Quso is increased when elevated levels of TC II are anticipated, as, eg, in severe jaundice. All the rapid methods tested yielded clinically significant results in patients with myeloproliferative disorders.
Quantitative aspects of glucose and glutamine metabolism by intestinal cells.
Authors: E A Newsholme, A L Carrie
Journal: Gut (1994)

Gut fuel utilisation has several unique features. Arterial and luminal fuels provide nutrition for the enterocyte, the former being of more importance. This factor, and the heterogeneity of cell types within the gut makes it difficult to define its fuel utilisation. Metabolic control logic suggests that modulation of the maximal activity of any pathway resides in those enzymes that operate in vivo at rates far below their maximal capacity and that catalyse non-equilibrium reactions. On this basis, although enterocyte hexokinase activity is much higher than in other 'glycolytic' cells (for example, brain), potentially high rates of glucose utilisation are modulated by substrate cycling of glucose 6-phosphate back to glucose through glucose 6-phosphatase. Glutamine metabolism proceeds by glutaminase to produce glutamate, which may then be transaminated (aspartate-aminotransferase and alanine-amino transferase) to produce alpha-ketoglutarate, alanine, and aspartate. The end products of glutamine metabolism by incubated gut preparations in vitro (mainly alanine), suggests that enterocytes, not immune cells, are responsible for most gut glutamine metabolism. High flux rates of glucose and glutamine metabolism in the enterocyte may result from the need for de novo synthesis of purines and pyrimidines and ribose sugars for nucleic acid synthesis. Sepsis reduces rates of glucose and glutamine metabolism, perhaps to preserve the increased consumption of these fuels by activated lymphocytes and macrophages in the gut wall.
Dapagliflozin Versus Glipizide as Add-on Therapy in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control With Metformin
Authors: Michael A. Nauck, Stefano Del Prato, Juris J. Meier, Santiago Durán-García, Katja Rohwedder, Martina Elze, Shamik J. Parikh
Journal: Diabetes Care (2011)

OBJECTIVE Although initially effective, sulfonylureas are associated with poor glycemic durability, weight gain, and hypoglycemia. Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects. We compared the efficacy, safety, and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy. RESEARCH DESIGN AND METHODS This 52-week, double-blind, multicenter, active-controlled, noninferiority trial randomized patients with type 2 diabetes (baseline mean HbA1c, 7.7%), who were receiving metformin monotherapy, to add-on dapagliflozin (n = 406) or glipizide (n = 408) up-titrated over 18 weeks, based on glycemic response and tolerability, to ≤10 or ≤20 mg/day, respectively. RESULTS The primary end point, adjusted mean HbA1c reduction with dapagliflozin (−0.52%) compared with glipizide (−0.52%), was statistically noninferior at 52 weeks. Key secondary end points: dapagliflozin produced significant adjusted mean weight loss (−3.2 kg) versus weight gain (1.2 kg; P &amp;lt; 0.0001) with glipizide, significantly increased the proportion of patients achieving ≥5% body weight reduction (33.3%) versus glipizide (2.5%; P &amp;lt; 0.0001), and significantly decreased the proportion experiencing hypoglycemia (3.5%) versus glipizide (40.8%; P &amp;lt; 0.0001). Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to standard treatment and rarely led to study discontinuation. CONCLUSIONS Despite similar 52-week glycemic efficacy, dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin. Long-term studies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors.
Influence of prehospital administration of aspirin and heparin on initial patency of the infarct-related artery in patients with acute st elevation myocardial infarction
Authors: Felix Zijlstra, Nicolette Ernst, Menko-Jan de Boer, Edwin Nibbering, Harry Suryapranata, Jan C.A Hoorntje, Jan-Henk E Dambrink, Arnoud W.J van’t Hof, Freek W.A Verheugt
Journal: Journal of the American College of Cardiology (2002)
Patient Controlled Analgesia
Authors: D. Rowbotham
Journal: BMJ (1995)

Edward Welchew BMJ Publishing Group, pounds sterling16.95, pp 133 ISBN 0 7279 0860 X

Our approach to managing postoperative pain has changed fundamentally over the past decade. Previously, most patients were fortunate if they received two or three doses of intramuscular opioid after major surgery. This despite numerous publications describing the excessive incidence of severe pain after surgery. There were probably two catalysts for change. Firstly, the report of the Royal Colleges of Anaesthetists and Surgeons on Pain After Surgery was published in 1991. It recommended a change in our attitude to postoperative pain, improved education, and the safe introduction of new pain management techniques into British hospitals. In general this was well received, and most hospitals have responded to it.

The second factor …
Zinc Transporter 8 Antibodies Complement GAD and IA-2 Antibodies in the Identification and Characterization of Adult-Onset Autoimmune Diabetes
Authors: Vito Lampasona, Antonio Petrone, Claudio Tiberti, Marco Capizzi, Marialuisa Spoletini, Sergio di Pietro, Marco Songini, Sara Bonicchio, Francesco Giorgino, Ezio Bonifacio, Emanuele Bosi, Raffaella Buzzetti
Journal: Diabetes Care (2009)

OBJECTIVE Zinc transporter 8 (ZnT8) is an islet β-cell secretory granule membrane protein recently identified as an autoantibody antigen in type 1 diabetes. The aim of this study was to determine the prevalence and role of antibodies to ZnT8 (ZnT8As) in adult-onset diabetes. RESEARCH DESIGN AND METHODS ZnT8As were measured by a radioimmunoprecipitation assay using recombinant ZnT8 COOH-terminal or NH2-terminal proteins in 193 patients with adult-onset autoimmune diabetes having antibodies to either GAD (GADAs) or IA-2 (IA-2As) and in 1,056 antibody-negative patients with type 2 diabetes from the Non Insulin Requiring Autoimmune Diabetes (NIRAD) study. RESULTS ZnT8As-COOH were detected in 18.6% patients with autoimmune diabetes and 1.4% with type 2 diabetes. ZnT8As-NH2 were rare. ZnT8As were associated with younger age and a high GADA titer. The use of GADAs, IA-2As, and ZnT8As in combination allowed a stratification of clinical phenotype, with younger age of onset of diabetes and characteristics of more severe insulin deficiency (higher fasting glucose and A1C, lower BMI, total cholesterol, and triglycerides) in patients with all three markers, with progressive attenuation in patients with two, one, and no antibodies (all Ptrend &amp;lt; 0.001). Autoantibody titers, association with high-risk HLA genotypes, and prevalence of thyroid peroxidase antibodies followed the same trend (all P &amp;lt; 0.001). CONCLUSIONS ZnT8As are detectable in a proportion of patients with adult-onset autoimmune diabetes and seem to be a valuable marker to differentiate clinical phenotypes.
Scintigraphic assessment of oesophageal motility: what does it show and how reliable is it?
Authors: M M Mughal, M Marples, J Bancewicz
Journal: Gut (1986)

Computer analysed transit of a liquid bolus containing Tc99m (RT) was compared with manometry for the detection of oesophageal motility disorders in 151 patients with a variety of oesophageal symptoms. Manometry was abnormal in 99 of whom 44 had abnormal RT (sensitivity 44%); it was normal in 52 of whom 37 had normal RT (specificity 71%). The commonest manometric abnormalities were non-specific motility disorders characterised by abnormalities of peristaltic amplitude, waveform or baseline. Radionuclide transit was abnormal in only 32/77 (42%) of these. Achalasia, which is characterised by complete aperistalsis, was the least common diagnosis, but all five cases had abnormal RT. Simultaneous manometry and RT in 30 patients showed that the transit of a liquid bolus through the oesophagus is determined by the propagation rather than the form of the peristaltic contraction. Because non-specific motility disorders are common in clinical practice, RT is not a useful screening test for oesophageal dysmotility.
When a woman asks for a caesarean section.
Authors: J G Thornton, R J Lilford
Journal: BMJ (1987)

highly variable.This surely also applies to bone accretion.In a remote complex of villages in western Transvaal, where all families are fairly poor and subsist on a similar frugal, near veg- etarian diet, we found considerable differences between children, aged 10-12 years", not only in cortical indices of metacarpal but also in haemo- globin, serum cholesterol, and albumin concentra- tions and transit time.Such variability could not be explained by differences in diet.It would seem that the determinants of bone mass are not understood fully and that bone mass is susceptible to little modification, whether in reach- ing maximal accretion or during subsequent loss with age.
An investigation into the effects of smoking on physical fitness parameters in adolescents
Authors: Shobhit Saxena, Douglas McBean
Journal: British Journal of Sports Medicine (2010)

Smoking is associated both prognostically and aetiologically with numerous diseases of the respiratory system. Tobacco smoking is a major cause of an accelerated decline in ventilatory function and physical fitness. As most of the people take to smoking when they are young, it will be informative to study the effects of smoking on lungs in the initial stages. The aims of this study were to investigate the effects of smoking on forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ) and maximal oxygen consumption (VO 2 max) in adolescent smokers. Methods An experimental study subject design was carried out on 15 smoking and 15 non-smoking volunteers within the age group of 18–30 years who were recruited from the college campus. The non-smokers formed the control group. All the subjects underwent spirometric analysis and maximal treadmill test (Bruce protocol) for the estimation of VO 2 max. Appropriate statistical tests were performed to study the effects 30 min after smoking a cigarette. Results There was a statistically significant difference in the mean spirometric values of FVC/FEV 1 of the smokers and the non-smokers; however, there was no statistically significant difference in the mean VO 2 max value in smokers and non-smokers. There was a statistically significant difference in the mean FVC/FEV 1 of the smokers before and 30 min after smoking a cigarette. Again there was no statistically significant difference in the mean VO 2 max values before and after smoking a cigarette in the smokers. Conclusion Cigarette smoking does have a significant effect on the spirometric values of FVC/FEV 1 ; however, its effect on the maximal oxygen consumption (VO 2 max) could not be ascertained accurately in adolescent smokers.
Copper in diseases and treatments, and copper‐based anticancer strategies
Authors: Francesco Tisato, Cristina Marzano, Marina Porchia, Maura Pellei, Carlo Santini
Journal: Medicinal Research Reviews (2009)

Copper is found in all living organisms and is a crucial trace element in redox chemistry, growth and development. It is important for the function of several enzymes and proteins involved in energy metabolism, respiration, and DNA synthesis, notably cytochrome oxidase, superoxide dismutase, ascorbate oxidase, and tyrosinase. The major functions of copper-biological molecules involve oxidation-reduction reactions in which they react directly with molecular oxygen to produce free radicals. Therefore, copper requires tightly regulated homeostatic mechanisms to ensure adequate supplies without any toxic effects. Overload or deficiency of copper is associated, respectively, with Wilson disease (WD) and Menkes disease (MD), which are of genetic origin. Researches on Menkes and Wilson disorders have provided useful insights in the field of copper homeostasis and in particular into the understanding of intracellular trafficking and distribution of copper at molecular levels. Therapies based on metal supplementation with copper histidine or removal of copper excess by means of specific copper chelators are currently effective in treating MD and WD, respectively. Copper chelation therapy is now attracting much attention for the investigation and treatment of various neurodegenerative disorders such as Alzheimer, Parkinson and CreutzfeldtJakob. An excess of copper appears to be an essential co-factor for angiogenesis. Moreover, elevated levels of copper have been found in many types of human cancers, including prostate, breast, colon, lung, and brain. On these basis, the employment of copper chelators has been reported to be of therapeutic value in the treatment of several types of cancers as anti-angiogenic molecules. More recently, mixtures of copper chelators with copper salts have been found to act as efficient proteasome inhibitors and apoptosis inducers, specifically in cancer cells. Moreover, following the worldwide success of platinum(II) compounds in cancer chemotherapy, several families of individual copper complexes have been studied as potential antitumor agents. These investigations, revealing the occurrence of mechanisms of action quite different from platinum drugs, head toward the development of new anticancer metallodrugs with improved specificity and decreased toxic side effects.
Neutropenia and anemia with reduced serum vitamin B<sub>12</sub>
Authors: Rajesh Krishna, Emma O'Donovan, Barbara J. Bain
Journal: American Journal of Hematology (2010)

A 55-year-old man presented with excessive tiredness and shivering at night. Nothing of note was found on physical examination. He was known to suffer from Crohn's disease and 10 years previously had been found to be deficient in vitamin B12 and had been treated briefly. A full blood count on this occasion showed pancytopenia: WBC 0.9 × 109/l, neutrophils 0.1 × 109/l, hemoglobin concentration 8.5 g/dl, mean cell volume 96 fl and platelet count 219 × 109/l. Serum B12 was below the level that could be quantified by the laboratory, <83 ng/l (normal range 160-800), confirmed on a repeat specimen. His peripheral blood film showed occasional blast cells and no neutrophil hypersegmentation. A bone marrow aspirate showed an increase both of cytologically normal proerythroblasts and of other primitive cells that were more pleomorphic than the proerythroblasts and had less cytoplasmic basophilia. The pleomorphic cells constituted 60% of bone marrow cells. Some of the mature erythroblasts had megaloblastic features. In view of the marked reduction of serum B12, the question arose as to whether the patient had a significant B12 deficiency, a hematological malignancy or both. Careful examination of the aspirate film showed some cells to contain Auer rods (Figure: red arrow, cell containing Auer rod; black arrow, proerythroblast, May–Grünwald–Giemsa). Sudan black B (SBB) staining confirmed the presence of Auer rods (Figure, inset) and showed some blast cells to have SBB-positive granules. A confident diagnosis of acute myeloid leukemia (AML) could therefore be made. The patient received daily vitamin B12 injections for 6 days with no alteration in counts and a repeat bone marrow examination showed that megaloblasts were still present. On flow cytometry the blast cells expressed CD13, CD33, CD34, CD117, HLA-DR and myeloperoxidase. Misdiagnosis of severe megaloblastic anaemia as erythroleukemia is a well recognized pitfall. In this patient there was the potential for misdiagnosis of AML as megaloblastic anemia. However the blood count would have been very atypical for B12 deficiency since the neutropenia was severe and yet there was no thrombocytopenia. The detection of Auer rods permitted an unequivocal diagnosis. It is quite likely that there was no tissue deficiency of B12 despite the low serum concentration. Tissue delivery of vitamin B12 depends on transcobalamin concentration whereas assays are measuring also vitamin B12 bound to haptocorrin.
In vivo metabolism of 3,2'-dimethyl-4-aminobiphenyl (DMAB) bearing on its organotropism in the Syrian golden hamster and the F344 rat.
Authors: M Nussbaum, E S Fiala, B Kulkarni, K El-Bayoumy, J H Weisburger
Journal: Environmental Health Perspectives (1983)

The in vivo metabolism of tritiated DMAB was examined in male Syrian golden hamsters, which are susceptible to both urinary bladder and intestinal carcinogenesis by this agent and in male F344 rats in which intestinal tumors represent the main lesions. Evidence was obtained for the presence of the N-hydroxy-N-glucuronide of DMAB as a major metabolite in hamster urine and bile and in rat bile but not urine. The routes of excretion of this metabolite, which may represent a transport form of the ultimate carcinogen, correlate well with the main tumor sites in the two species. Other metabolites partially identified were the sulfates and glucuronides of C-hydroxylated DMAB and C-hydroxylated-N-acetyl DMAB.
Histopathologic Effects of Ultrasonically Induced Hyperthermia in Intraocular Malignant Melanoma
Authors: D. Jackson Coleman, Ronald H. Silverman, Takeo Iwamoto, Frederic L. Lizzi, Mark J. Rondeau, Jack Driller, Angel Rosado, David H. Abramson, Robert M. Ellsworth
Journal: Ophthalmology (1988)
Hyperglycemia with Relative Hypoinsulinemia in Diphenylhydantoin Toxicity
Authors: Bruce H. Peters, Naguib A. Samaan
Journal: New England Journal of Medicine (1969)

A RECENTLY recognized toxic effect of diphenylhydantoin (Dilantin, DPH) overdosage is a reversible hyperglycemia.1 2 3 We have studied a case of reversible hyperglycemia, with defective serum insul...