abstract: @entity4727 -like peptides and messenger RNA (mRNA) have recently been detected in neural tissues, but it is uncertain whether this reflects the transcription of the @entity4727 gene or that of a closely related gene. This possibility has, therefore, been investigated. @entity4727 -like complementary DNA (cDNA) moieties of predicted size were readily generated from reverse transcribed brain ( @entity1640 and extrahypothalamic tissue) and pituitary RNA, using polymerase chain reaction (PCR) with three sets of overlapping oligonucleotide primers designed to amplify @entity4727 cDNA fragments of 285, 372, and 459 base pairs (bp). PCR reamplification of the largest @entity1640 moiety with an internal set of primers also generated a cDNA fragment of the predicted size (372 bp). Restriction endonuclease digestion with BstNI cleaved the largest @entity1640 cDNA moieties into smaller fragments of 217 and 242 bp, identical to the cleavage of parathyroidal @entity4727 cDNA. Rapid amplification of cDNA ends of the 3'-flanking cDNA sequences also produced @entity1640 and extra- @entity1640 cDNA moieties identical in size (499 bp) to parathyroidal @entity4727 cDNA. Southern analysis of these PCR and rapid amplification of cDNA end cDNA fragments further indicated homology with @entity4727 cDNA. This homology was subsequently confirmed by @entity377 sequencing, which demonstrated complete homology between the neural and parathyroidal cDNA fragments. This homology extended over 673 bp (spanning nucleotides 31-709 of @entity4727 cDNA), encompassing 95% of the entire parathyroidal @entity4727 cDNA. The mRNA for this gene, determined by Northern blotting with a riboprobe for @entity4727 mRNA, was of identical size to the parathyroidal @entity4727 , but its abundance in brain was less than 0.01% of that expressed in the parathyroid glands. This transcript was not, however, detected in liver. The translation of this moiety in @entity1640 tissues was indicated by the presence of a protein in the @entity35 hypothalamus that was immunoreactive with @entity4727 ) antiserum and of comparable size to that in parathyroidal tissue. The abundance of this protein in @entity1640 tissue was approximately 0.25% of that in the parathyroid glands, suggesting tissue-specific differences in its rate of synthesis, processing, or degradation. These results, therefore, demonstrate that the brain is an extraparathyroidal site of @entity4727 gene expression and suggest autocrine or paracrine roles for @entity4727 in neural function.

title: Sequence analysis of XXXX parathyroid hormone messenger ribonucleic acid.

entities_list: @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide']

entities_list: @entity1640 :: ('MESH:D007027', 'Disease') :: ['hypothalamic']

answer: @entity1640 :: (MESH:D007027,Disease) :: ['hypothalamic']


abstract: 11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the conversion of @entity701 to @entity821 and @entity2819 to @entity19672 . This activity may be required to confer normal ligand specificity upon the @entity19673 . Although an isozyme of 11-HSD was previously isolated from @entity35 liver, a different isozyme is apparently expressed in mineralocorticoid target tissues. We isolated a @entity742 kidney cDNA clone encoding this isozyme by expression screening using @entity1238 oocytes. The cDNA is 1.8 kb in length and encodes a protein of 427 @entity535 residues with a predicted M(r) of 46,700. When expressed in oocytes, this enzyme functions as an @entity2125 -dependent 11 beta-hydrogenase with very high affinity for @entity230 , but it has no detectable reductase activity. It is 37% identical in @entity535 sequence to an @entity2125 -dependent isozyme of @entity19674 dehydrogenase, but only 20% identical to the @entity1110 -dependent liver isozyme of 11-HSD. It is expressed at high levels in the kidney and adrenal and at lower levels in the colon. The corresponding gene is present in a single copy in the @entity742 genome. In @entity1 , this gene is a candidate locus for the syndrome of apparent mineralocorticoid excess, a form of @entity101 postulated to result from 11-HSD deficiency in mineralocorticoid target tissues.

title: Cloning of cDNA encoding an @entity2125 -dependent isoform of 11 beta-hydroxysteroid dehydrogenase in XXXX kidney.

entities_list: @entity230 :: ('MESH:D013256', 'Chemical') :: ['steroids']

entities_list: @entity821 :: ('MESH:D003348', 'Chemical') :: ['cortisone']

entities_list: @entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension']

entities_list: @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid']

entities_list: @entity19674 :: ('CHEBI:35343', 'Chemical') :: ['17 beta-hydroxysteroid']

entities_list: @entity2819 :: ('MESH:D003345', 'Chemical') :: ['corticosterone']

entities_list: @entity19673 :: ('443144(Tax:9940)', 'Gene') :: ['mineralocorticoid receptor']

entities_list: @entity701 :: ('MESH:D006854', 'Chemical') :: ['cortisol']

entities_list: @entity19672 :: ('MESH:C003552', 'Chemical') :: ['11-dehydrocorticosterone']

answer: @entity742 :: (9940,Species) :: ['sheep']


abstract: 11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the conversion of @entity701 to @entity821 and @entity2819 to @entity19672 . This activity may be required to confer normal ligand specificity upon the @entity19673 . Although an isozyme of 11-HSD was previously isolated from @entity35 liver, a different isozyme is apparently expressed in mineralocorticoid target tissues. We isolated a @entity742 kidney cDNA clone encoding this isozyme by expression screening using @entity1238 oocytes. The cDNA is 1.8 kb in length and encodes a protein of 427 @entity535 residues with a predicted M(r) of 46,700. When expressed in oocytes, this enzyme functions as an @entity2125 -dependent 11 beta-hydrogenase with very high affinity for @entity230 , but it has no detectable reductase activity. It is 37% identical in @entity535 sequence to an @entity2125 -dependent isozyme of @entity19674 dehydrogenase, but only 20% identical to the @entity1110 -dependent liver isozyme of 11-HSD. It is expressed at high levels in the kidney and adrenal and at lower levels in the colon. The corresponding gene is present in a single copy in the @entity742 genome. In @entity1 , this gene is a candidate locus for the syndrome of apparent mineralocorticoid excess, a form of @entity101 postulated to result from 11-HSD deficiency in mineralocorticoid target tissues.

title: Cloning of cDNA encoding an XXXX -dependent isoform of 11 beta-hydroxysteroid dehydrogenase in @entity742 kidney.

answer: @entity2125 :: (MESH:D009243,Chemical) :: ['NAD(+)']


abstract: We present an 18-month @entity1 with @entity2645 poisoning to illustrate the neuro-cardiac toxic effects of this potentially deadly poison in @entity1 . The toddler ingested an unknown amount of @entity2645 from a non-childproof bottle which clearly labelled that the drug must be kept out of reach from @entity1 . He developed @entity16 . Electrocardiography (ECG) showed @entity591 and widened QRS. He was immediately treated with @entity3157 infusion and made an uneventful recovery. This is the youngest and only reported case of symptomatic @entity2645 ingestion in our locality. @entity2645 has been surpassed by newer antidepressants for the treatment of @entity308 in the past decade. Literature is searched to review the mortality rate in young @entity1 . Intensive care neuro-cardiac support contributes to the favorable outcome. Despite clear labelling of the bottle, carelessness on the part of the adult and the use of non-childproof bottle are definite preventable factor to such potentially fatal ingestion.

title: Neurologic and Cardiovascular Complications in Pediatric Life Threatening XXXX Poisoning.

entities_list: @entity1 :: ('9606', 'Species') :: ['children', 'boy']

entities_list: @entity308 :: ('MESH:D003866', 'Disease') :: ['depression']

entities_list: @entity16 :: ('MESH:D009422', 'Disease') :: ['neurologic and cardiac symptoms']

entities_list: @entity3157 :: ('CHEBI:17544', 'Chemical') :: ['bicarbonate']

entities_list: @entity591 :: ('MESH:D013610', 'Disease') :: ['tachycardia']

entities_list: @entity2645 :: ('MESH:D007099', 'Chemical') :: ['imipramine', 'Imipramine']

answer: @entity2645 :: (MESH:D007099,Chemical) :: ['Imipramine']


abstract: OBJECTIVE: We sought to determine the economic costs associated with moderate and late @entity600 . DESIGN: An economic study was nested within a prospective cohort study. SAMPLE: @entity1 born between 32(+0) and 36(+6)   weeks of gestation in the East Midlands of England. A sample of @entity1 born at >= 37  weeks of gestation acted as controls. METHODS: Data on resource use, estimated from a National Health Service (NHS) and personal social services perspective, and separately from a societal perspective, were collected between birth and 24  months corrected age (or @entity204 ), and valued in pounds sterling, at 2010-11 prices. Descriptive statistics and multivariable analyses were used to estimate the relationship between gestational age at birth and economic costs. MAIN OUTCOME MEASURES: Cumulative resource use and economic costs over the first two years of life. RESULTS: Of all eligible births, 1146 (83%) preterm and 1258 (79%) term @entity1 were recruited. Mean (standard error) total societal costs from birth to 24  months were   12  037 (  1114) and   5823 (  1232) for @entity1 born moderately preterm (32(+0) -33(+6)   weeks of gestation) and late preterm (34(+0) -36(+6)   weeks of gestation), respectively, compared with   2056 (  132) for @entity1 born at term. The mean societal cost difference between moderate and late preterm and term @entity1 was   4657 (bootstrap 95% confidence interval, 95%  CI   2513-6803; P  <  0.001). Multivariable regressions revealed that, after controlling for clinical and sociodemographic characteristics, moderate and late @entity600 increased societal costs by   7583 (  874) and   1963 (  337), respectively, compared with birth at full term. CONCLUSIONS: Moderate and late @entity600 is associated with significantly increased economic costs over the first 2  years of life. Our economic estimates can be used to inform budgetary and service planning by clinical decision-makers, and economic evaluations of interventions aimed at preventing moderate and late @entity600 or alleviating its adverse consequences. TWEETABLE ABSTRACT: Moderate and late @entity600 is associated with increased economic costs over the first 2 years of life.

title: Economic costs associated with moderate and late XXXX : a prospective population-based study.

entities_list: @entity1 :: ('9606', 'Species') :: ['children', 'infants', 'Infants']

entities_list: @entity600 :: ('MESH:D000014', 'Disease') :: ['preterm birth']

answer: @entity600 :: (MESH:D000014,Disease) :: ['preterm birth']


abstract: Although @entity27120 (ANP) has been detected in the plasma of late gestation fetal @entity742 , stimuli that control its secretion and its function in regulating fluid volume are unclear. To determine stimuli that increase ANP secretion and to ascertain whether the response is a function of gestation we studied 20 chronically cannulated fetal @entity742 . The fetuses were divided into 3 groups; Group I (age range 118-129 days), Group II (age range 129-141 days) and Group III (age range 127-137 days) gestation. Arterial pressure was increased to within a physiologic range by infusing @entity2647 at 6 micrograms/min at 0.1 ml/min into the inferior vena cava of the fetus (Groups I and II). Corrected for body weight fetuses in Group I received 2 micrograms/kg/min whereas fetuses in Group II received 1.66 micrograms/kg/min. In the fetuses in Group III preload to the right side of the heart was increased by inflating an occluder cuff was placed around the ductus arteriosus. Systemic mean arterial pressure (MAP) increased significantly in fetuses in Groups I and II. Plasma ANP concentrations increased significantly in all fetuses. Plasma @entity17955 Activity (PRA) decreased significantly in the fetuses in Group II. These results suggest that @entity2647 infusion and closure of the ductus arteriosus in utero increase circulating ANP in fetal @entity742 .

title: Effects of XXXX induced increase in arterial pressure and closure of the ductus arteriosus on the secretion of @entity27120 (ANP) and @entity17955 in the ovine fetus.

entities_list: @entity27120 :: ('100294648(Tax:9940)', 'Gene') :: ['atrial natriuretic peptide']

entities_list: @entity2647 :: ('MESH:D010656', 'Chemical') :: ['phenylephrine']

answer: @entity2647 :: (MESH:D010656,Chemical) :: ['phenylephrine']


abstract: Although @entity27120 (ANP) has been detected in the plasma of late gestation fetal @entity742 , stimuli that control its secretion and its function in regulating fluid volume are unclear. To determine stimuli that increase ANP secretion and to ascertain whether the response is a function of gestation we studied 20 chronically cannulated fetal @entity742 . The fetuses were divided into 3 groups; Group I (age range 118-129 days), Group II (age range 129-141 days) and Group III (age range 127-137 days) gestation. Arterial pressure was increased to within a physiologic range by infusing @entity2647 at 6 micrograms/min at 0.1 ml/min into the inferior vena cava of the fetus (Groups I and II). Corrected for body weight fetuses in Group I received 2 micrograms/kg/min whereas fetuses in Group II received 1.66 micrograms/kg/min. In the fetuses in Group III preload to the right side of the heart was increased by inflating an occluder cuff was placed around the ductus arteriosus. Systemic mean arterial pressure (MAP) increased significantly in fetuses in Groups I and II. Plasma ANP concentrations increased significantly in all fetuses. Plasma @entity17955 Activity (PRA) decreased significantly in the fetuses in Group II. These results suggest that @entity2647 infusion and closure of the ductus arteriosus in utero increase circulating ANP in fetal @entity742 .

title: Effects of @entity2647 induced increase in arterial pressure and closure of the ductus arteriosus on the secretion of @entity27120 (ANP) and XXXX in the ovine fetus.

answer: @entity17955 :: (443310(Tax:9940),Gene) :: ['renin']


abstract: Although @entity27120 (ANP) has been detected in the plasma of late gestation fetal @entity742 , stimuli that control its secretion and its function in regulating fluid volume are unclear. To determine stimuli that increase ANP secretion and to ascertain whether the response is a function of gestation we studied 20 chronically cannulated fetal @entity742 . The fetuses were divided into 3 groups; Group I (age range 118-129 days), Group II (age range 129-141 days) and Group III (age range 127-137 days) gestation. Arterial pressure was increased to within a physiologic range by infusing @entity2647 at 6 micrograms/min at 0.1 ml/min into the inferior vena cava of the fetus (Groups I and II). Corrected for body weight fetuses in Group I received 2 micrograms/kg/min whereas fetuses in Group II received 1.66 micrograms/kg/min. In the fetuses in Group III preload to the right side of the heart was increased by inflating an occluder cuff was placed around the ductus arteriosus. Systemic mean arterial pressure (MAP) increased significantly in fetuses in Groups I and II. Plasma ANP concentrations increased significantly in all fetuses. Plasma @entity17955 Activity (PRA) decreased significantly in the fetuses in Group II. These results suggest that @entity2647 infusion and closure of the ductus arteriosus in utero increase circulating ANP in fetal @entity742 .

title: Effects of @entity2647 induced increase in arterial pressure and closure of the ductus arteriosus on the secretion of XXXX (ANP) and @entity17955 in the ovine fetus.

answer: @entity27120 :: (100294648(Tax:9940),Gene) :: ['atrial natriuretic peptide']


abstract: Most animal and @entity1 studies show that @entity9541 reduce serum/or plasma total @entity165 and low density lipoprotein (LDL) @entity165 levels. @entity9541 are structurally very similar to @entity165 except that they always contain some substitutions at the C24 position on the @entity5068 side chain. Plasma @entity37161 levels in @entity1 tissue are normally very low due primarily to poor absorption from the intestine and @entity409 compared to @entity165 . @entity9541 are able to be metabolized in the liver into C21 bile acids via liver other than normal C24 bile acids in mammals. It is generally assumed that @entity165 reduction results directly from inhibition of @entity165 absorption through displacement of @entity165 from micelles. Structure-specific effects of individual @entity37161 constituents have recently been shown where saturated @entity9541 are more efficient compared to unsaturated compounds in reducing @entity165 levels. In addition, @entity9541 produce a wide spectrum of therapeutic effects in animals including anti- @entity5 properties. @entity9541 have been shown experimentally to inhibit @entity694 development. With regard to @entity137 , no obvious side effects of @entity37161 have been observed in studies to date, except in individual with @entity25589 , an @entity74 . Further characterization of the influence of various @entity37161 subcomponents on lipoprotein profiles in @entity1 is required to maximize the usefulness of this non-pharmacological approach to reduction of @entity731 in the population.

title: Dietary XXXX : a review of metabolism, benefits and side effects.

entities_list: @entity1 :: ('9606', 'Species') :: ['mammalian', 'human', 'humans']

entities_list: @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity']

entities_list: @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumour']

entities_list: @entity25589 :: ('MESH:C537345', 'Disease') :: ['phytosterolemia']

entities_list: @entity409 :: ('MESH:D008107', 'Disease') :: ['faster excretion from liver']

entities_list: @entity37161 :: ('CHEBI:28824', 'Chemical') :: ['phytosterol']

entities_list: @entity74 :: ('MESH:D030342', 'Disease') :: ['inherited lipid disorder']

entities_list: @entity9541 :: ('MESH:D010840', 'Chemical') :: ['phytosterols', 'Phytosterols']

entities_list: @entity694 :: ('MESH:D003110', 'Disease') :: ['colon cancer']

entities_list: @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']

answer: @entity9541 :: (MESH:D010840,Chemical) :: ['phytosterols']


abstract: The plasmid-borne pheBA operon of @entity15250 PaW85 allows growth of the host cells on @entity3971 . The promoter of this operon is activated by the chromosomally encoded LysR-type regulator CatR, in the presence of the inducer @entity22761 . @entity22761 is an intermediate of @entity6153 degradation by the chromosomally encoded ortho or beta-ketoadipate pathway. The catBC operon encodes two enzymes of the beta-ketoadipate pathway and also requires CatR and @entity22761 for its expression. The promoters of the pheBA and catBC operons are highly homologous, and since both respond to CatR, it is likely that the pheBA promoter was recruited from the ancestral catBC promoter. Gel shift assays and DNase I footprinting have shown that the pheBA promoter has a higher binding affinity for CatR than the catBC promoter. Like the catBC promoter, the pheBA promoter forms two complexes (C1 and C2) with CatR in the absence of @entity22761 , but only forms a single complex (C2) in the presence of @entity22761 . Like the catBC promoter CatR @entity3337 ( @entity3337 ) and @entity3457 ( @entity3457 ) arrangement, the pheBA promoter demonstrates the presence of a 26 bp segment highly homologous to the @entity3337 that is protected by CatR from DNase I digestion in the absence of the inducer. An additional 16 bp sequence, similar to the catBC promoter @entity3457 , is protected only when the inducer @entity22761 is present. The binding of CatR in absence of @entity22761 bends the catBC and pheBA promoter regions to significantly different degrees, but CatR binding in the presence of @entity22761 results in a similar degree of DNA bending. The evolutionary implications of the interactions of CatR with these two promoters are discussed.

title: Differential DNA bending introduced by the XXXX LysR-type regulator, CatR, at the plasmid-borne pheBA and chromosomal catBC promoters.

entities_list: @entity15250 :: ('303', 'Species') :: ['Pseudomonas putida strain']

entities_list: @entity3457 :: ('OMIM:612348', 'Disease') :: ['ABS', 'activation binding site']

entities_list: @entity22761 :: ('MESH:C005939', 'Chemical') :: ['cis,cis-muconate', 'cis-cis-muconate']

entities_list: @entity3337 :: ('MESH:D009371', 'Disease') :: ['RBS', 'repression binding site']

entities_list: @entity6153 :: ('MESH:C034221', 'Chemical') :: ['catechol']

answer: @entity15250 :: (303,Species) :: ['Pseudomonas putida']


abstract: We have examined phosphorylation of @entity11451 in cultured sympathetic neurons and PC12 cells. Dissociated @entity35 superior cervical ganglion neurons or PC12 cells were incubated with 32Pi to label cellular phosphoproteins. Membrane proteins were solubilized, and @entity11451 proteins were immunoprecipitated with the monoclonal antibody 192-IgG. Analysis by @entity3208 - @entity2975 gel electrophoresis and autoradiography showed that @entity11451 components of Mr = 80,000 and Mr = 210,000 were phosphorylated. Phosphorylation of neither species was affected by treating the cells with NGF or @entity1359 . When the 80,000-Da protein was subjected to complete trypsin proteolysis and then analyzed by reverse phase liquid chromatography, two 32P-labeled peptides were resolved. The more hydrophobic peptide accounted for most of the 32P and contained only @entity8283 ; the other peptide contained @entity8283 and @entity8284 . No @entity10393 was detected in the receptor proteins. When receptor molecules from nonlabeled PC12 cells were immunoprecipitated and then incubated in vitro with [gamma-32P] @entity855 and the @entity268 -independent protein kinase FA/GSK-3, phosphorylation occurred predominantly on @entity563 and to a lesser extent on @entity1889 . However, the immunoprecipitated receptor proteins neither autophosphorylated nor were they detectably phosphorylated by @entity268 -dependent protein kinase, casein kinase II, or protein kinase C (the @entity141 /phospholipid-dependent enzyme). We conclude that binding units of the @entity11451 are phosphorylated constitutively in at least two sites in intact cells and that they can be phosphorylated by FA/GSK-3 in vitro.

title: Phosphorylation of nerve growth factor receptor proteins in sympathetic neurons and PC12 cells. In vitro phosphorylation by the XXXX -independent protein kinase FA/GSK-3.

entities_list: @entity8283 :: ('CHEBI:15811', 'Chemical') :: ['phosphoserine']

entities_list: @entity3208 :: ('MESH:D012967', 'Chemical') :: ['sodium dodecyl sulfate']

entities_list: @entity10393 :: ('CHEBI:74956', 'Chemical') :: ['phosphotyrosine']

entities_list: @entity1359 :: ('CHEBI:37537', 'Chemical') :: ['phorbol 12-myristate 13-acetate']

entities_list: @entity11451 :: ('24596(Tax:10116)', 'Gene') :: ['nerve growth factor (NGF) receptor', 'NGF receptor']

entities_list: @entity2975 :: ('CHEBI:51135', 'Chemical') :: ['polyacrylamide']

entities_list: @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine']

entities_list: @entity1889 :: ('CHEBI:26986', 'Chemical') :: ['threonine']

entities_list: @entity8284 :: ('CHEBI:37525', 'Chemical') :: ['phosphothreonine']

answer: @entity268 :: (CHEBI:17489,Chemical) :: ['cAMP']


abstract: We are presenting our experience with vertebral body resection in forty-seven operative procedures in forty @entity1 with a @entity5 . The indication for surgery was neural relapse after previous radiotherapy in eighteen procedures, the need for a tissue diagnosis in sixteen, a radioresistant @entity5 in seven, @entity1274 while receiving radiotherapy in five, and a pathological @entity174 in one. In thirty-three procedures (70 per cent) the level of compression was in the thoracic spine. Replacement of the resected vertebral bodies was achieved by anterior instrumentation and the use of @entity3677 in twenty-one procedures (45 per cent), while bone-grafting, cement, and instrumentation in various combinations were used in the remainder. Before surgery all of the @entity1 had some @entity51 . The @entity1 was still able to walk prior to twelve (26 per cent) of the procedures, was paraparetic prior to twenty-three (49 per cent), and was paraplegic prior to twelve (26 per cent). Bowel and @entity1494 was present before twenty-five (53 per cent). The outcome of only forty-four procedures could be evaluated because three @entity1 died postoperatively. The @entity1 was able to walk following thirty-five (80 per cent) of the procedures, was paraparetic after eight (18 per cent), and was still paraplegic after one. The @entity1 regained normal sphincter control after forty-one (93 per cent) of the procedures. Three (6 per cent) of the procedures were followed by the death of the @entity1 , and complications occurred after five (11 per cent) of the procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Vertebral body resection for epidural compression by XXXX . Results of forty-seven consecutive operative procedures.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'patient']

entities_list: @entity174 :: ('MESH:D050723', 'Disease') :: ['fracture-dislocation']

entities_list: @entity1494 :: ('MESH:D001745', 'Disease') :: ['bladder dysfunction']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'malignant epidural tumor']

entities_list: @entity51 :: ('MESH:D009461', 'Disease') :: ['neural deficit']

entities_list: @entity1274 :: ('MESH:D006319', 'Disease') :: ['neural deterioration']

entities_list: @entity3677 :: ('MESH:D020366', 'Chemical') :: ['methylmethacrylate']

answer: @entity5 :: (MESH:D009369,Disease) :: ['malignant tumors']


abstract: The regulation of pituitary @entity6659 ( @entity6659 ) receptor concentration was investigated in @entity35 with antero-lateral cuts (ALC) placed around the hypothalamus, as well as in Brattleboro homozygotes (HO) that genetically suffer from a lack of AVP. @entity1640 caused a reduction in (3H)-AVP binding, while counteracting the dramatic fall in binding that normally occurs after adrenalectomy. Surprisingly, in HO @entity35 , long-term adrenalectomy did cause pituitary AVP receptor number to decrease to an extent similar to that seen in normal @entity35 . However, the receptor disappeared twice as rapidly in heterozygote controls than in HO animals, with calculated half-lives of 1.1 and 2.0 days, respectively. In HO, chronic administration of @entity6659 reduced receptor concentration by about 80%, while the same dose of @entity398 (OT) produced only a 20-30% reduction. Whereas @entity619 injections did reverse the depressing effect of adrenalectomy on pituitary AVP receptors, they failed to enhance binding in sham-operated controls, treated or not with @entity6659 ; thereby suggesting a central site of action of the @entity134 . In contrast, in @entity35 with @entity1640 ALCs (i.e. with the pituitary lacking central control), @entity2819 implants did antagonize the reduction in receptor density caused by adrenalectomy. We conclude that the pituitary AVP receptor system lies mainly under control of the central nervous system, through a mechanism of action that not only seems to imply AVP and OT, but probably also some other @entity1640 factor(s). Glucocorticoids appear to exert a dual effect, acting indirectly through negative feedback control of neuropeptide release and, possibly, also directly on the pituitary to regulate binding sites.

title: Central nervous system control of pituitary XXXX receptors: evidence for involvement of multiple factors.

entities_list: @entity398 :: ('MESH:D010121', 'Chemical') :: ['oxytocin']

entities_list: @entity1640 :: ('MESH:D007027', 'Disease') :: ['hypothalamic', 'Hypothalamic ALCs']

entities_list: @entity2819 :: ('MESH:D003345', 'Chemical') :: ['corticosterone']

entities_list: @entity619 :: ('MESH:D003907', 'Chemical') :: ['dexamethasone']

entities_list: @entity134 :: ('CHEBI:35341', 'Chemical') :: ['steroid']

entities_list: @entity6659 :: ('MESH:D020790', 'Disease') :: ['VP', 'vasopressin']

answer: @entity6659 :: (MESH:D020790,Disease) :: ['vasopressin']


abstract: In previous studies, we have shown that ultraviolet (UV) B radiation perturbs the @entity1412 function of Langerhans cells (LC) by interfering with as-yet unidentified co-stimulatory signals. Recently, @entity12750 on @entity1412 were shown to deliver important co-stimulatory signals through interaction with their counter receptors @entity1361 and @entity4386 on T cells. To determine whether UVB affects the functional expression of @entity7938 or @entity2937 on LC, @entity12750 expression was studied on @entity1 LC by multiparameter flow cytometry. Little, if any, @entity7938 or @entity2937 was detected on LC freshly isolated from skin. However, following 48 h of tissue culture, expression of both @entity12750 were markedly up-regulated. To test whether these molecules were functional, primary mixed epidermal cell leukocyte reactions (MECLR) were performed. Blocking monoclonal antibody (mAb) to @entity7938 or @entity2937 both inhibited the MECLR, with anti- @entity2937 being much more effective than anti- @entity7938 . UVB radiation dose-dependently (100-200 J/m2) suppressed the culture-induced up-regulation of @entity7938 and @entity2937 on LC. Since LC exposed to the same UVB flux (UVB-LC) failed to stimulate alloreactive T cells in a MECLR, we questioned whether this was related to their inability to provide B7 co-stimulation. Indeed, when effective B7- @entity1361 signaling was ascertained by adding submitogenic doses of exogenous anti- @entity1361 mAb to UVB-LC, the proliferative response of alloreactive T cells was restored. We conclude that the suppressive effects of low-dose UVB radiation on the @entity1412 function of LC are, at least in part, due to an inhibition of functional @entity12750 expression.

title: Low-dose UVB radiation perturbs the functional expression of XXXX co-stimulatory molecules on @entity1 Langerhans cells.

answer: @entity12750 :: (941;942,Gene) :: ['B7.1 and B7.2']


abstract: In previous studies, we have shown that ultraviolet (UV) B radiation perturbs the @entity1412 function of Langerhans cells (LC) by interfering with as-yet unidentified co-stimulatory signals. Recently, @entity12750 on @entity1412 were shown to deliver important co-stimulatory signals through interaction with their counter receptors @entity1361 and @entity4386 on T cells. To determine whether UVB affects the functional expression of @entity7938 or @entity2937 on LC, @entity12750 expression was studied on @entity1 LC by multiparameter flow cytometry. Little, if any, @entity7938 or @entity2937 was detected on LC freshly isolated from skin. However, following 48 h of tissue culture, expression of both @entity12750 were markedly up-regulated. To test whether these molecules were functional, primary mixed epidermal cell leukocyte reactions (MECLR) were performed. Blocking monoclonal antibody (mAb) to @entity7938 or @entity2937 both inhibited the MECLR, with anti- @entity2937 being much more effective than anti- @entity7938 . UVB radiation dose-dependently (100-200 J/m2) suppressed the culture-induced up-regulation of @entity7938 and @entity2937 on LC. Since LC exposed to the same UVB flux (UVB-LC) failed to stimulate alloreactive T cells in a MECLR, we questioned whether this was related to their inability to provide B7 co-stimulation. Indeed, when effective B7- @entity1361 signaling was ascertained by adding submitogenic doses of exogenous anti- @entity1361 mAb to UVB-LC, the proliferative response of alloreactive T cells was restored. We conclude that the suppressive effects of low-dose UVB radiation on the @entity1412 function of LC are, at least in part, due to an inhibition of functional @entity12750 expression.

title: Low-dose UVB radiation perturbs the functional expression of @entity12750 co-stimulatory molecules on XXXX Langerhans cells.

answer: @entity1 :: (9606,Species) :: ['human']


abstract: A case of an anteriorly located @entity1653 in the region of the foramen magnum, successfully treated by a transoral approach, is reported. A 60-year-old @entity1 was admitted to the author's department on January 19th, 1983. Six years before admission, she began to experience the gradual cold dysesthesia in the both palms, and then developed gait disturbance, clumsiness of the right hand and a stiffneck. She was found to have @entity194 , mild @entity508 , @entity2055 and hypalgesia under the bilateral C2 spinal levels. A CT scan disclosed a patchy @entity75 , which was enhanced homogenously with contrast medium, occupying almost all the intradural extramedullary space at the foramen magnum. The transoral approach was employed following preliminary tracheostomy. The @entity5 , extending about one centimeter superiorly to the basion and inferiorly to the upper border of C2 body, was removed completely, and then the dural defect was covered with a piece of fascia and gelform. An anterior occipitocervical fusion was performed extending to C2 using a block of an antogenous iliac bone. Post-operatively immobilization was secured by a Halo-Vest. But unexpectedly, CSF leakage was disclosed several days after the surgery without @entity16 . On the 17th day following first surgery, a re-operation was performed. The dural defect was successfully repaired with a piece of fascia by interrupted sutures in an illustrated fashion (Fig. 5). A piece of muscle was then placed in the epidural space created by bone removal. A fusion of the atlanto-axial joint not extending to the basiocciput was employed.(ABSTRACT TRUNCATED AT 250 WORDS)

title: [Transoral anterior approach to foramen magnum XXXX --a case report and review].

entities_list: @entity75 :: ('MESH:D001927', 'Disease') :: ['hyperdense lesion']

entities_list: @entity508 :: ('MESH:D009128', 'Disease') :: ['spastic tetraparesis']

entities_list: @entity16 :: ('MESH:D009422', 'Disease') :: ['neurological deterioration']

entities_list: @entity1653 :: ('MESH:D008579', 'Disease') :: ['meningioma']

entities_list: @entity194 :: ('MESH:D001284', 'Disease') :: ['atrophied hands']

answer: @entity1653 :: (MESH:D008579,Disease) :: ['meningioma']


abstract: BACKGROUND: Linkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F(2) populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. @entity1442 ( @entity1442 ) are produced by repeated intercrossing of F(2) animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few @entity1442 datasets, all originating from inbred founders, have been reported in the literature. METHODS: We have produced a nine-generation @entity1442 pedigree (n = 1529) from two outbred @entity1573 lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F(2) population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all @entity1442 individuals to replicate the detection of and fine-map QTL affecting juvenile body weight. RESULTS: Five of the nine QTL detected with the original F(2) population were confirmed and fine-mapped with the @entity1442 , while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL. CONCLUSIONS: Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using @entity1442 . Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred @entity1442 populations will increase the number of organisms for which in-depth complex traits can be analyzed.

title: Fine mapping and replication of QTL in outbred XXXX advanced intercross lines.

entities_list: @entity1442 :: ('MESH:D020178', 'Disease') :: ['AIL', 'Advanced Intercross Lines']

answer: @entity1573 :: (9031,Species) :: ['chicken']


abstract: PURPOSE: To prospectively compare an investigational version of a complex-based chemical shift-based fat fraction magnetic resonance (MR) imaging method with MR spectroscopy for the quantification of @entity1560 . MATERIALS AND METHODS: This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained before all studies. Fifty-five @entity1 (31 @entity1 , 24 @entity1 ; age range, 24-71 years) were prospectively imaged at 1.5 T with quantitative MR imaging and single-voxel MR spectroscopy, each within a single breath hold. The effects of T2 correction, spectral modeling of fat, and magnitude fitting for eddy current correction on fat quantification with MR imaging were investigated by reconstructing fat fraction images from the same source data with different combinations of error correction. Single-voxel T2-corrected MR spectroscopy was used to measure fat fraction and served as the reference standard. All MR spectroscopy data were postprocessed at a separate institution by an MR physicist who was blinded to MR imaging results. Fat fractions measured with MR imaging and MR spectroscopy were compared statistically to determine the correlation (r(2)), and the slope and intercept as measures of agreement between MR imaging and MR spectroscopy fat fraction measurements, to determine whether MR imaging can help quantify fat, and examine the importance of T2 correction, spectral modeling of fat, and eddy current correction. Two-sided t tests (significance level, P = .05) were used to determine whether estimated slopes and intercepts were significantly different from 1.0 and 0.0, respectively. Sensitivity and specificity for the classification of clinically significant @entity1560 were evaluated. RESULTS: Overall, there was excellent correlation between MR imaging and MR spectroscopy for all reconstruction combinations. However, agreement was only achieved when T2 correction, spectral modeling of fat, and magnitude fitting for eddy current correction were used (r(2) = 0.99; slope    standard deviation = 1.00    0.01, P = .77; intercept    standard deviation = 0.2%    0.1, P = .19). CONCLUSION: T1-independent chemical shift-based water-fat separation MR imaging methods can accurately quantify fat over the entire liver, by using MR spectroscopy as the reference standard, when T2 correction, spectral modeling of fat, and eddy current correction methods are used.

title: Quantification of XXXX with T1-independent, T2-corrected MR imaging with spectral modeling of fat: blinded comparison with MR spectroscopy.

entities_list: @entity1 :: ('9606', 'Species') :: ['women', 'patients', 'men']

entities_list: @entity1560 :: ('MESH:D005234', 'Disease') :: ['hepatic steatosis', 'steatosis']

answer: @entity1560 :: (MESH:D005234,Disease) :: ['hepatic steatosis']


abstract: PURPOSE: @entity172 receptor-positive (ER+) and -negative (ER) @entity0 are molecularly distinct diseases. We hypothesized that @entity876 mutations may lead to different transcriptional changes and carry different prognostic value in these two different types of @entity5 . EXPERIMENTAL DESIGN: We developed a 39-gene @entity876 signature derived from 213 ER+ and a separate 30-gene signature from 38 @entity5 with known mutation status and tested their prognostic and chemotherapy response predictive values in ER+ and @entity5 , respectively. RESULTS: External validation to predict @entity876 status (n = 103) showed sensitivity and specificity of 89% and 54% for the 39-gene signature, and 82% and 61% for the 30-gene signature. The 39-gene signature was predictive of worse distant @entity3 free survival in ER+ @entity5 in two separate prognostic data sets (n = 255, HR: 2.3, P = 0.005 and n = 198, HR: 2.17, P = 0.09). It also predicted for poor prognosis even with adjuvant @entity440 therapy (n = 277, HR = 2.43, P < 0.0001) but it was not prognostic in @entity5 . It was also associated with higher chemotherapy sensitivity in ER+ but not in @entity5 . The prognostic and predictive values remained significant in multivariate analysis. The 30-gene, ER-, @entity876 signature showed no prognostic or predictive values in ER+ @entity5 but it was associated with better prognosis in @entity5 . It also had no chemotherapy response predictive value in ER- or ER+ @entity5 . CONCLUSIONS: @entity876 dysfunction is prognostically most relevant in ER+ @entity5 and supports the hypothesis that different predictive or prognostic markers will be needed for different molecular subsets of @entity0 .

title: Distinct XXXX gene signatures are needed to predict prognosis and response to chemotherapy in ER-positive and ER-negative @entity0 .

entities_list: @entity172 :: ('MESH:D004967', 'Chemical') :: ['Estrogen']

entities_list: @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancers', 'breast cancer']

entities_list: @entity440 :: ('MESH:D013629', 'Chemical') :: ['tamoxifen']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'ER- cancers']

entities_list: @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis']

answer: @entity876 :: (7157,Gene) :: ['p53']


abstract: PURPOSE: @entity172 receptor-positive (ER+) and -negative (ER) @entity0 are molecularly distinct diseases. We hypothesized that @entity876 mutations may lead to different transcriptional changes and carry different prognostic value in these two different types of @entity5 . EXPERIMENTAL DESIGN: We developed a 39-gene @entity876 signature derived from 213 ER+ and a separate 30-gene signature from 38 @entity5 with known mutation status and tested their prognostic and chemotherapy response predictive values in ER+ and @entity5 , respectively. RESULTS: External validation to predict @entity876 status (n = 103) showed sensitivity and specificity of 89% and 54% for the 39-gene signature, and 82% and 61% for the 30-gene signature. The 39-gene signature was predictive of worse distant @entity3 free survival in ER+ @entity5 in two separate prognostic data sets (n = 255, HR: 2.3, P = 0.005 and n = 198, HR: 2.17, P = 0.09). It also predicted for poor prognosis even with adjuvant @entity440 therapy (n = 277, HR = 2.43, P < 0.0001) but it was not prognostic in @entity5 . It was also associated with higher chemotherapy sensitivity in ER+ but not in @entity5 . The prognostic and predictive values remained significant in multivariate analysis. The 30-gene, ER-, @entity876 signature showed no prognostic or predictive values in ER+ @entity5 but it was associated with better prognosis in @entity5 . It also had no chemotherapy response predictive value in ER- or ER+ @entity5 . CONCLUSIONS: @entity876 dysfunction is prognostically most relevant in ER+ @entity5 and supports the hypothesis that different predictive or prognostic markers will be needed for different molecular subsets of @entity0 .

title: Distinct @entity876 gene signatures are needed to predict prognosis and response to chemotherapy in ER-positive and ER-negative XXXX .

answer: @entity0 :: (MESH:D001943,Disease) :: ['breast cancers']


abstract: BACKGROUND: @entity121 has high relevance in @entity1 performance. Most authors agree that the use of the median frequency is preferred as a fatigue indicator. Most work has to date, been done on dynamic fatigue measurements, using the similarity index (SI). OBJECTIVE: Repeated trunk flexion-extensions were measured using the B200 Isostation. Muscle activity was recorded by surface electromyography (EMG) in order to evaluate fatigue of trunk flexor and extensor muscles. Twenty male university students participated in this pilot study, including 6 apparently healthy subjects with a history of @entity1643 ( @entity1643 ), and 14 healthy matched controls. All @entity1 were instructed to perform repeated trunk flexion-extension against 50% of their back extensors maximal @entity2472 (MVCs) resistance until they could no longer perform the task. The SI was calculated from quantitative analysis of EMG data recording during dynamic trunk flexion extension task. Median frequency was also measured before and after fatiguing contractions. RESULTS: The results of this study revealed a significant decrease in the SI and median frequency measurements following fatigue in both groups (p< 0.05). CONCLUSION: The results of this study indicated that in both groups changes in SI measurements following fatigue are in agreement with the changes in median frequency measurements.

title: @entity121 in subjects with a history of XXXX and a group of healthy controls measured by similarity index.

entities_list: @entity1 :: ('9606', 'Species') :: ['participants', 'human']

entities_list: @entity1643 :: ('MESH:D017116', 'Disease') :: ['low back pain', 'LBP']

entities_list: @entity121 :: ('MESH:D009135', 'Disease') :: ['Trunk muscle fatigue']

entities_list: @entity2472 :: ('MESH:C536214', 'Disease') :: ['volutary contractions']

answer: @entity1643 :: (MESH:D017116,Disease) :: ['low back pain']


abstract: BACKGROUND: @entity121 has high relevance in @entity1 performance. Most authors agree that the use of the median frequency is preferred as a fatigue indicator. Most work has to date, been done on dynamic fatigue measurements, using the similarity index (SI). OBJECTIVE: Repeated trunk flexion-extensions were measured using the B200 Isostation. Muscle activity was recorded by surface electromyography (EMG) in order to evaluate fatigue of trunk flexor and extensor muscles. Twenty male university students participated in this pilot study, including 6 apparently healthy subjects with a history of @entity1643 ( @entity1643 ), and 14 healthy matched controls. All @entity1 were instructed to perform repeated trunk flexion-extension against 50% of their back extensors maximal @entity2472 (MVCs) resistance until they could no longer perform the task. The SI was calculated from quantitative analysis of EMG data recording during dynamic trunk flexion extension task. Median frequency was also measured before and after fatiguing contractions. RESULTS: The results of this study revealed a significant decrease in the SI and median frequency measurements following fatigue in both groups (p< 0.05). CONCLUSION: The results of this study indicated that in both groups changes in SI measurements following fatigue are in agreement with the changes in median frequency measurements.

title: XXXX in subjects with a history of @entity1643 and a group of healthy controls measured by similarity index.

answer: @entity121 :: (MESH:D009135,Disease) :: ['Trunk muscle fatigue']


abstract: PURPOSE: Medical educators frequently use standardized @entity1 (SP) encounters to bridge the gap between didactic education and practical application. Typically, SPs are healthy adults with no consistent physical findings; however, highly immersive virtual @entity1 (VHs) may enable the consistent presentation of abnormal physical findings to multiple learners across multiple repetitions. Thus, the authors conducted this study to compare how frequently junior anesthesiology residents suspected @entity27 ( @entity27 ) in preoperative assessments of SPs versus a VH. METHOD: The authors presented a @entity1 whose case included the historical features of @entity27 (snoring, daytime fatigue, observed @entity386 , @entity101 , and @entity28 ). Three SPs (in 2008) and one VH (in 2009) were necessary to run the residents through the assessment. The VH appeared morbidly @entity28 and had a neck circumference of 40 cm [corrected]. An airway exam of the VH displayed an image of redundant soft tissue, prominent tongue, and @entity1184 . The VH responded to natural speech by recognizing "triggers" in a @entity1 's voice. The 849 triggers and 259 VH responses were designed with a technique that collects information from user interactions. RESULTS: Five of 21 residents (23.8%) suspected @entity27 after interviewing the SPs, whereas 11 of 13 residents (84.6%) suspected @entity27 after interviewing the VH (odds ratio of 17.6; 95% CI of 2.9-107). CONCLUSIONS: Residents suspected @entity27 much more frequently after interviewing the VH than after interviewing the SPs. The VH provides a unique opportunity to display numerous abnormal physical findings as part of SP encounters.

title: Virtual XXXX versus standardized @entity1 : which lead residents to more correct diagnoses?

entities_list: @entity1 :: ('9606', 'Species') :: ['humans', 'human', 'patient']

entities_list: @entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension']

entities_list: @entity28 :: ('MESH:D009765', 'Disease') :: ['obese', 'obesity']

entities_list: @entity1184 :: ('MESH:D006984', 'Disease') :: ['tonsillar hypertrophy']

entities_list: @entity27 :: ('MESH:D020181', 'Disease') :: ['obstructive sleep apnea', 'OSA']

answer: @entity1 :: (9606,Species) :: ['humans']


abstract: PURPOSE: Medical educators frequently use standardized @entity1 (SP) encounters to bridge the gap between didactic education and practical application. Typically, SPs are healthy adults with no consistent physical findings; however, highly immersive virtual @entity1 (VHs) may enable the consistent presentation of abnormal physical findings to multiple learners across multiple repetitions. Thus, the authors conducted this study to compare how frequently junior anesthesiology residents suspected @entity27 ( @entity27 ) in preoperative assessments of SPs versus a VH. METHOD: The authors presented a @entity1 whose case included the historical features of @entity27 (snoring, daytime fatigue, observed @entity386 , @entity101 , and @entity28 ). Three SPs (in 2008) and one VH (in 2009) were necessary to run the residents through the assessment. The VH appeared morbidly @entity28 and had a neck circumference of 40 cm [corrected]. An airway exam of the VH displayed an image of redundant soft tissue, prominent tongue, and @entity1184 . The VH responded to natural speech by recognizing "triggers" in a @entity1 's voice. The 849 triggers and 259 VH responses were designed with a technique that collects information from user interactions. RESULTS: Five of 21 residents (23.8%) suspected @entity27 after interviewing the SPs, whereas 11 of 13 residents (84.6%) suspected @entity27 after interviewing the VH (odds ratio of 17.6; 95% CI of 2.9-107). CONCLUSIONS: Residents suspected @entity27 much more frequently after interviewing the VH than after interviewing the SPs. The VH provides a unique opportunity to display numerous abnormal physical findings as part of SP encounters.

title: Virtual @entity1 versus standardized XXXX : which lead residents to more correct diagnoses?

answer: @entity1 :: (9606,Species) :: ['patients']


abstract: Tracheobronchial epithelial (TBE) cells that normally do not express the squamous cell differentiation marker gene, @entity56113 , can be induced to produce it by @entity864 ( @entity865 ). The regulation of @entity56113 gene expression by @entity865 occurs, in part, at the transcriptional level in primary @entity1 and monkey TBE cells. Using a transient transfection assay, we observed that @entity865 stimulates the activity of the reporter gene, @entity2755 acetyltransferase, by 2-4-fold in transfected TBE cells. However, this @entity2755 acetyltransferase activity is cell type-specific with significantly less activity in transformed epithelial cell lines and no activity in non-epithelial cell types. @entity865 -dependent stimulation can also be demonstrated by co-transfection with plasmid DNAs that overexpress the JUN family of proteins, especially @entity1178 . Overexpression of @entity1178 and @entity865 treatment synergistically stimulate the @entity56113 promoter activity by more than 40-fold. Deletion analysis of the promoter region demonstrates that the DNA fragment of the first 98 base pairs of the 5'-flanking region contains the basal promoter activity, while the region between -162 and -96 contains the cis-enhancer elements for both the basal and @entity865 / @entity1178 -stimulating promoter activities. This observation is supported by in vivo genomic footprinting studies that reveal persistent protections in the following motifs of this region: -141 TRE, -131 GT, -123 ETS-like, and -111 TRE-like motifs and in the enhanced protections in -141 TRE and -111 TRE-like motifs in cells after the @entity865 treatment. Site-directed mutagenesis in this region demonstrates the involvement of both -141 TRE and -111 TRE-like motifs in @entity865 / @entity1178 -dependent stimulation as well as enhanced basal transcriptional activity. However, it is primarily the -111 TRE-like motif that is involved in the mediation of the enhanced basal promoter activity of the @entity1 @entity56113 gene. These results are further supported by gel mobility shift assays that demonstrate the involvement of @entity1178 and these TRE motifs in the formation of the DNA-protein complex.

title: Expression of @entity1 squamous cell differentiation marker, XXXX , in tracheobronchial epithelium depends on JUN and TRE motifs.

entities_list: @entity2755 :: ('MESH:D002701', 'Chemical') :: ['chloramphenicol']

entities_list: @entity864 :: ('MESH:C554292|MESH:D013755', 'Chemical') :: ['12-O-tetradecanoylphorbol-13-acetate']

answer: @entity56113 :: (170680,Gene) :: ['SPR1']


abstract: Tracheobronchial epithelial (TBE) cells that normally do not express the squamous cell differentiation marker gene, @entity56113 , can be induced to produce it by @entity864 ( @entity865 ). The regulation of @entity56113 gene expression by @entity865 occurs, in part, at the transcriptional level in primary @entity1 and monkey TBE cells. Using a transient transfection assay, we observed that @entity865 stimulates the activity of the reporter gene, @entity2755 acetyltransferase, by 2-4-fold in transfected TBE cells. However, this @entity2755 acetyltransferase activity is cell type-specific with significantly less activity in transformed epithelial cell lines and no activity in non-epithelial cell types. @entity865 -dependent stimulation can also be demonstrated by co-transfection with plasmid DNAs that overexpress the JUN family of proteins, especially @entity1178 . Overexpression of @entity1178 and @entity865 treatment synergistically stimulate the @entity56113 promoter activity by more than 40-fold. Deletion analysis of the promoter region demonstrates that the DNA fragment of the first 98 base pairs of the 5'-flanking region contains the basal promoter activity, while the region between -162 and -96 contains the cis-enhancer elements for both the basal and @entity865 / @entity1178 -stimulating promoter activities. This observation is supported by in vivo genomic footprinting studies that reveal persistent protections in the following motifs of this region: -141 TRE, -131 GT, -123 ETS-like, and -111 TRE-like motifs and in the enhanced protections in -141 TRE and -111 TRE-like motifs in cells after the @entity865 treatment. Site-directed mutagenesis in this region demonstrates the involvement of both -141 TRE and -111 TRE-like motifs in @entity865 / @entity1178 -dependent stimulation as well as enhanced basal transcriptional activity. However, it is primarily the -111 TRE-like motif that is involved in the mediation of the enhanced basal promoter activity of the @entity1 @entity56113 gene. These results are further supported by gel mobility shift assays that demonstrate the involvement of @entity1178 and these TRE motifs in the formation of the DNA-protein complex.

title: Expression of XXXX squamous cell differentiation marker, @entity56113 , in tracheobronchial epithelium depends on JUN and TRE motifs.

answer: @entity1 :: (9606,Species) :: ['human']


abstract: @entity699 attributable to hypersecretion of ACTH by a @entity977 is an uncommon and progressively lethal disease. Because of its rarity, it has been difficult to collect a large series of @entity1 in order to identify the prognostic factors influencing the outcome after transsphenoidal surgery. We conducted a multicenter, retrospective analysis of the early and late results of surgical treatment of @entity699 . Files of @entity1 with @entity699 who underwent transsphenoidal surgery between 1975 and 1990 were collected from 25 institutions throughout Europe. Data from 668 of 716 @entity1 were suitable for statistical analyses. Surgical mortality was 1.9%, and major morbidity occurred in 97 @entity1 (14.5%). Clinical and biochemical remission of @entity699 after surgery occurred in 510 cases (76.3%). Identification of the @entity5 by neuroradiological imaging or at operation with histopathological corroboration was associated with remission of @entity699 . Recurrence of the disease occurred in 65 (12.7%) of 510 @entity1 in remission after surgery at a mean time of 39.3 months (range 6-104 months). The distribution of the recurrences did not show any apparent plateau or cluster throughout the follow-up period. Low postoperative @entity134 levels, absence of @entity701 response to @entity6192 , and the need for long-term glucocorticoid substitution therapy were all associated with a high probability of long-term remission. Our study demonstrates that transsphenoidal surgery is a safe and effective treatment for @entity1 with @entity699 . However, after successful surgery there is a steady increase in the percentage of recurrences, which continues with time. @entity1 who after operation had @entity509 and needed long-term glucocorticoid substitution therapy had the lowest risk of relapse.

title: Factors influencing the immediate and late outcome of XXXX treated by transsphenoidal surgery: a retrospective study by the European @entity699 Survey Group.

entities_list: @entity1 :: ('9606', 'Species') :: ['Patients', 'patients']

entities_list: @entity699 :: ('MESH:D003480', 'Disease') :: ['Hypercortisolism', "Cushing's disease", 'hypercortisolism']

entities_list: @entity509 :: ('MESH:C538429', 'Disease') :: ['hypoadrenocorticism']

entities_list: @entity134 :: ('CHEBI:35341', 'Chemical') :: ['steroid']

entities_list: @entity977 :: ('MESH:D010911', 'Disease') :: ['pituitary adenoma']

entities_list: @entity701 :: ('MESH:D006854', 'Chemical') :: ['cortisol']

answer: @entity699 :: (MESH:D003480,Disease) :: ['Cushing's disease']


abstract: @entity699 attributable to hypersecretion of ACTH by a @entity977 is an uncommon and progressively lethal disease. Because of its rarity, it has been difficult to collect a large series of @entity1 in order to identify the prognostic factors influencing the outcome after transsphenoidal surgery. We conducted a multicenter, retrospective analysis of the early and late results of surgical treatment of @entity699 . Files of @entity1 with @entity699 who underwent transsphenoidal surgery between 1975 and 1990 were collected from 25 institutions throughout Europe. Data from 668 of 716 @entity1 were suitable for statistical analyses. Surgical mortality was 1.9%, and major morbidity occurred in 97 @entity1 (14.5%). Clinical and biochemical remission of @entity699 after surgery occurred in 510 cases (76.3%). Identification of the @entity5 by neuroradiological imaging or at operation with histopathological corroboration was associated with remission of @entity699 . Recurrence of the disease occurred in 65 (12.7%) of 510 @entity1 in remission after surgery at a mean time of 39.3 months (range 6-104 months). The distribution of the recurrences did not show any apparent plateau or cluster throughout the follow-up period. Low postoperative @entity134 levels, absence of @entity701 response to @entity6192 , and the need for long-term glucocorticoid substitution therapy were all associated with a high probability of long-term remission. Our study demonstrates that transsphenoidal surgery is a safe and effective treatment for @entity1 with @entity699 . However, after successful surgery there is a steady increase in the percentage of recurrences, which continues with time. @entity1 who after operation had @entity509 and needed long-term glucocorticoid substitution therapy had the lowest risk of relapse.

title: Factors influencing the immediate and late outcome of @entity699 treated by transsphenoidal surgery: a retrospective study by the European XXXX Survey Group.

answer: @entity699 :: (MESH:D003480,Disease) :: ['Cushing's Disease']


abstract: A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in @entity1 . However, how age, sex @entity134 hormones, and @entity28 singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 microgram/L) and high sensitivity and specificity (> or = 90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese @entity1 , whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum @entity442 ( @entity442 ), @entity10116 ( @entity10116 ), and @entity2301 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 micrograms/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = -0.610; P < 0.01). In contrast, @entity251 was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum @entity251 concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum @entity251 (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum @entity53 (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum @entity53 (r = -0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex @entity230 . The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum @entity442 concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = -0.611; P = 0.009).(ABSTRACT TRUNCATED AT 400 WORDS)

title: Differential impact of age, sex XXXX hormones, and @entity28 on basal versus pulsatile growth hormone secretion in @entity1 as assessed in an ultrasensitive chemiluminescence assay.

entities_list: @entity251 :: ('MESH:D013739', 'Chemical') :: ['testosterone']

entities_list: @entity28 :: ('MESH:D009765', 'Disease') :: ['obesity']

entities_list: @entity442 :: ('3479', 'Gene') :: ['insulin-like growth factor I', 'IGF-I']

entities_list: @entity53 :: ('MESH:D004958', 'Chemical') :: ['estradiol']

entities_list: @entity230 :: ('MESH:D013256', 'Chemical') :: ['steroids']

answer: @entity134 :: (CHEBI:35341,Chemical) :: ['steroid']


abstract: A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in @entity1 . However, how age, sex @entity134 hormones, and @entity28 singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 microgram/L) and high sensitivity and specificity (> or = 90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese @entity1 , whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum @entity442 ( @entity442 ), @entity10116 ( @entity10116 ), and @entity2301 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 micrograms/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = -0.610; P < 0.01). In contrast, @entity251 was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum @entity251 concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum @entity251 (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum @entity53 (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum @entity53 (r = -0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex @entity230 . The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum @entity442 concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = -0.611; P = 0.009).(ABSTRACT TRUNCATED AT 400 WORDS)

title: Differential impact of age, sex @entity134 hormones, and XXXX on basal versus pulsatile growth hormone secretion in @entity1 as assessed in an ultrasensitive chemiluminescence assay.

answer: @entity28 :: (MESH:D009765,Disease) :: ['obesity']


abstract: A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in @entity1 . However, how age, sex @entity134 hormones, and @entity28 singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 microgram/L) and high sensitivity and specificity (> or = 90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese @entity1 , whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum @entity442 ( @entity442 ), @entity10116 ( @entity10116 ), and @entity2301 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 micrograms/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = -0.610; P < 0.01). In contrast, @entity251 was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum @entity251 concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum @entity251 (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum @entity53 (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum @entity53 (r = -0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex @entity230 . The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum @entity442 concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = -0.611; P = 0.009).(ABSTRACT TRUNCATED AT 400 WORDS)

title: Differential impact of age, sex @entity134 hormones, and @entity28 on basal versus pulsatile growth hormone secretion in XXXX as assessed in an ultrasensitive chemiluminescence assay.

answer: @entity1 :: (9606,Species) :: ['men']


abstract: Octreotide ( @entity2390 ) is a synthetic analog of @entity1943 , an endogenous GH inhibitory peptide that has been used as an adjunct to surgery and radiotherapy in the treatment of @entity2012 . When given sc in divided daily doses, it lowers serum GH to less than 5 micrograms/L in approximately 50% of cases. Data suggest that continuous infusions of @entity1943 analogs may be more effective in lowering GH. We have evaluated @entity73208 , a new long-acting preparation of Sandostatin, in eight @entity1 with @entity2012 . After an initial pharmacokinetic study, @entity1 received a minimum of 10 im injections of @entity73208 (20, 30, or 40 mg) at 28- or 42-day intervals. Serum GH levels decreased from 10.7 +/- 2.8 micrograms/L (mean +/- SE) at baseline to a nadir of 2.6 +/- 0.4 micrograms/L after the tenth injection, and to less than 5 micrograms/L in every patient. Serum insulin-like growth factor-I decreased from 927 +/- 108 ng/mL at baseline to 472 +/- 59 ng/mL at the end of the sixth injection and returned to normal (< 500 ng/mL) in seven of the eight @entity1 . This was associated with significant improvements in @entity10 , @entity4841 , and sweating. There was no evidence of @entity2390 accumulation, and the drug was well tolerated. To date, no @entity5990 have occurred, and serial pituitary imaging has revealed no increase in the size of the initial @entity977 . In particular, two previously untreated @entity1 have shown complete regression of the initial microadenoma and have serum GH values of less than 2.5 micrograms/L. @entity73208 is an effective and well-tolerated treatment for @entity1 with @entity2012 . Undoubtedly the initial indication for @entity73208 will be in the @entity1 who is not cured after surgery and radiotherapy, but our experience suggests that it may be used as a primary treatment in some acromegalics.

title: Depot long-acting XXXX analog ( @entity73208 ) is an effective treatment for @entity2012 .

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'patient']

entities_list: @entity5990 :: ('MESH:D042882', 'Disease') :: ['gallstones']

entities_list: @entity2012 :: ('MESH:D000172', 'Disease') :: ['acromegaly']

entities_list: @entity73208 :: ('MESH:C541923', 'Chemical') :: ['Sandostatin-LAR']

entities_list: @entity977 :: ('MESH:D010911', 'Disease') :: ['pituitary tumor']

entities_list: @entity2390 :: ('MESH:D015282', 'Chemical') :: ['octreotide', 'Sandostatin']

entities_list: @entity4841 :: ('MESH:D018771', 'Disease') :: ['arthralgia']

entities_list: @entity1943 :: ('MESH:D013004', 'Chemical') :: ['somatostatin']

entities_list: @entity10 :: ('MESH:D006261', 'Disease') :: ['headache']

answer: @entity1943 :: (MESH:D013004,Chemical) :: ['somatostatin']


abstract: Octreotide ( @entity2390 ) is a synthetic analog of @entity1943 , an endogenous GH inhibitory peptide that has been used as an adjunct to surgery and radiotherapy in the treatment of @entity2012 . When given sc in divided daily doses, it lowers serum GH to less than 5 micrograms/L in approximately 50% of cases. Data suggest that continuous infusions of @entity1943 analogs may be more effective in lowering GH. We have evaluated @entity73208 , a new long-acting preparation of Sandostatin, in eight @entity1 with @entity2012 . After an initial pharmacokinetic study, @entity1 received a minimum of 10 im injections of @entity73208 (20, 30, or 40 mg) at 28- or 42-day intervals. Serum GH levels decreased from 10.7 +/- 2.8 micrograms/L (mean +/- SE) at baseline to a nadir of 2.6 +/- 0.4 micrograms/L after the tenth injection, and to less than 5 micrograms/L in every patient. Serum insulin-like growth factor-I decreased from 927 +/- 108 ng/mL at baseline to 472 +/- 59 ng/mL at the end of the sixth injection and returned to normal (< 500 ng/mL) in seven of the eight @entity1 . This was associated with significant improvements in @entity10 , @entity4841 , and sweating. There was no evidence of @entity2390 accumulation, and the drug was well tolerated. To date, no @entity5990 have occurred, and serial pituitary imaging has revealed no increase in the size of the initial @entity977 . In particular, two previously untreated @entity1 have shown complete regression of the initial microadenoma and have serum GH values of less than 2.5 micrograms/L. @entity73208 is an effective and well-tolerated treatment for @entity1 with @entity2012 . Undoubtedly the initial indication for @entity73208 will be in the @entity1 who is not cured after surgery and radiotherapy, but our experience suggests that it may be used as a primary treatment in some acromegalics.

title: Depot long-acting @entity1943 analog ( XXXX ) is an effective treatment for @entity2012 .

answer: @entity73208 :: (MESH:C541923,Chemical) :: ['Sandostatin-LAR']


abstract: Octreotide ( @entity2390 ) is a synthetic analog of @entity1943 , an endogenous GH inhibitory peptide that has been used as an adjunct to surgery and radiotherapy in the treatment of @entity2012 . When given sc in divided daily doses, it lowers serum GH to less than 5 micrograms/L in approximately 50% of cases. Data suggest that continuous infusions of @entity1943 analogs may be more effective in lowering GH. We have evaluated @entity73208 , a new long-acting preparation of Sandostatin, in eight @entity1 with @entity2012 . After an initial pharmacokinetic study, @entity1 received a minimum of 10 im injections of @entity73208 (20, 30, or 40 mg) at 28- or 42-day intervals. Serum GH levels decreased from 10.7 +/- 2.8 micrograms/L (mean +/- SE) at baseline to a nadir of 2.6 +/- 0.4 micrograms/L after the tenth injection, and to less than 5 micrograms/L in every patient. Serum insulin-like growth factor-I decreased from 927 +/- 108 ng/mL at baseline to 472 +/- 59 ng/mL at the end of the sixth injection and returned to normal (< 500 ng/mL) in seven of the eight @entity1 . This was associated with significant improvements in @entity10 , @entity4841 , and sweating. There was no evidence of @entity2390 accumulation, and the drug was well tolerated. To date, no @entity5990 have occurred, and serial pituitary imaging has revealed no increase in the size of the initial @entity977 . In particular, two previously untreated @entity1 have shown complete regression of the initial microadenoma and have serum GH values of less than 2.5 micrograms/L. @entity73208 is an effective and well-tolerated treatment for @entity1 with @entity2012 . Undoubtedly the initial indication for @entity73208 will be in the @entity1 who is not cured after surgery and radiotherapy, but our experience suggests that it may be used as a primary treatment in some acromegalics.

title: Depot long-acting @entity1943 analog ( @entity73208 ) is an effective treatment for XXXX .

answer: @entity2012 :: (MESH:D000172,Disease) :: ['acromegaly']


abstract: BACKGROUND AND OBJECTIVE: The prescribing of extended regimens of oral contraceptives (OCs) is increasing in routine gynaecological practice as a means of reducing the number of annual @entity548 . Typically, this involves taking one pill per day for, say, 84 days continuously (4 21 days), followed by a 7-day pill-free interval. Low-dose OCs are suitable for extended use, and many gynaecologists in Germany prescribe the combination of @entity18831 2   mg/ @entity2082 0.03   mg (CMA 2   mg/EE 0.03   mg). The aim of the current study was to assess the risks and benefits of CMA 2   mg/EE 0.03   mg in extended regimens, using pooled data from observational studies. METHODS: This pooled analysis of three large-scale, non-interventional, observational studies assessed the results in @entity1 receiving Belara   (CMA 2   mg/EE 0.03   mg) according to an extended regimen compared with conventional regimens documented in the summary of product characteristics. RESULTS: A total of 625 @entity1 were identified as extended-regimen users (mean  SD age 24.9  9.0 years). Extended-cycle use was associated with @entity272 , dysmenorrhoea symptoms (as shown by reductions in analgesic use; absence from school, university, or work; and restrictions in leisure and sporting activities), cycle-dependent symptoms (e.g. @entity10 / @entity2704 , breast tenderness), @entity548 , bleeding duration and reduced libido. Mean bodyweight remained almost constant over 6 months. Only nine adverse drug reactions, none severe, were reported in eight @entity1 (1.3%). CONCLUSION: This pooled analysis confirms that extended regimens of CMA 2   mg/EE 0.03   mg reduce cycle-related complaints and are very well tolerated.

title: Extended cycles with the combined oral contraceptive XXXX 2   mg/ @entity2082 0.03   mg: pooled analysis of data from three large-scale, non-interventional, observational studies.

entities_list: @entity548 :: ('MESH:D006470', 'Disease') :: ['menstrual bleeds', 'withdrawal bleeding']

entities_list: @entity2082 :: ('MESH:D004997', 'Chemical') :: ['ethinylestradiol']

entities_list: @entity18831 :: ('MESH:D002715', 'Chemical') :: ['chlormadinone acetate']

entities_list: @entity272 :: ('MESH:D012871', 'Disease') :: ['decreases in skin problems']

answer: @entity18831 :: (MESH:D002715,Chemical) :: ['chlormadinone acetate']


abstract: BACKGROUND AND OBJECTIVE: The prescribing of extended regimens of oral contraceptives (OCs) is increasing in routine gynaecological practice as a means of reducing the number of annual @entity548 . Typically, this involves taking one pill per day for, say, 84 days continuously (4 21 days), followed by a 7-day pill-free interval. Low-dose OCs are suitable for extended use, and many gynaecologists in Germany prescribe the combination of @entity18831 2   mg/ @entity2082 0.03   mg (CMA 2   mg/EE 0.03   mg). The aim of the current study was to assess the risks and benefits of CMA 2   mg/EE 0.03   mg in extended regimens, using pooled data from observational studies. METHODS: This pooled analysis of three large-scale, non-interventional, observational studies assessed the results in @entity1 receiving Belara   (CMA 2   mg/EE 0.03   mg) according to an extended regimen compared with conventional regimens documented in the summary of product characteristics. RESULTS: A total of 625 @entity1 were identified as extended-regimen users (mean  SD age 24.9  9.0 years). Extended-cycle use was associated with @entity272 , dysmenorrhoea symptoms (as shown by reductions in analgesic use; absence from school, university, or work; and restrictions in leisure and sporting activities), cycle-dependent symptoms (e.g. @entity10 / @entity2704 , breast tenderness), @entity548 , bleeding duration and reduced libido. Mean bodyweight remained almost constant over 6 months. Only nine adverse drug reactions, none severe, were reported in eight @entity1 (1.3%). CONCLUSION: This pooled analysis confirms that extended regimens of CMA 2   mg/EE 0.03   mg reduce cycle-related complaints and are very well tolerated.

title: Extended cycles with the combined oral contraceptive @entity18831 2   mg/ XXXX 0.03   mg: pooled analysis of data from three large-scale, non-interventional, observational studies.

answer: @entity2082 :: (MESH:D004997,Chemical) :: ['ethinylestradiol']


abstract: BACKGROUND: @entity3393 is an approved symptomatic treatment for moderate to severe @entity195 that reduces the excitotoxic effects of hyperactive glutamatergic transmission. However, the exact mechanism of the effect of @entity3393 in @entity195 @entity1 is poorly understood. Importantly, the default mode network (DMN), which plays a key role in attention, is hypoactive in @entity195 and is under glutamatergic control. OBJECTIVE: To assess the effect of @entity3393 on the activity of the DMN in moderate to severe @entity195 . METHODS: Functional magnetic resonance imaging (MRI) data from 15 @entity1 with moderate to severe @entity195 , seven treated with @entity3393 (mean    SD age 77    8 years, mean    SD Mini-Mental State Examination [MMSE] score 16    5) and eight with placebo (mean    SD age 76    6 years, mean    SD MMSE score 13    1), were acquired at baseline (T0) and after 6 months of treatment (T6). Resting state components were extracted after spatial normalization in individual @entity1 with independent component analysis. The consistency of the components was assessed using ICASSO and the DMN was recognized through spatial correlation with a pre-defined template. Voxel-based statistical analyses were performed to study the change in DMN activity from T0 to T6 in the two groups. RESULTS: At T0, the two groups showed similar DMN activity except in the precuneus and cuneus, where the @entity1 who started treatment with @entity3393 had slightly greater activity (p < 0.05 corrected for familywise error [FWE]). The prospective comparison between T0 and T6 in the treated @entity1 showed increased DMN activation mapping in the precuneus (p < 0.05, FWE corrected), while the prospective comparison in the untreated @entity1 did not show significant changes. The treatment * time interaction term was significant at p < 0.05, FWE corrected. CONCLUSIONS: The results suggest a positive effect of @entity3393 treatment in @entity1 with moderate to severe @entity195 , resulting in an increased resting DMN activity in the precuneus region over 6 months. Future studies confirming the present findings are required to further demonstrate the beneficial effects of @entity3393 on the DMN in @entity195 .

title: Effect of @entity3393 on resting state default mode network activity in XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['patients']

entities_list: @entity3393 :: ('MESH:D008559', 'Chemical') :: ['Memantine', 'memantine']

entities_list: @entity195 :: ('MESH:D000544', 'Disease') :: ["Alzheimer's disease"]

answer: @entity195 :: (MESH:D000544,Disease) :: ['Alzheimer's disease']


abstract: BACKGROUND: @entity3393 is an approved symptomatic treatment for moderate to severe @entity195 that reduces the excitotoxic effects of hyperactive glutamatergic transmission. However, the exact mechanism of the effect of @entity3393 in @entity195 @entity1 is poorly understood. Importantly, the default mode network (DMN), which plays a key role in attention, is hypoactive in @entity195 and is under glutamatergic control. OBJECTIVE: To assess the effect of @entity3393 on the activity of the DMN in moderate to severe @entity195 . METHODS: Functional magnetic resonance imaging (MRI) data from 15 @entity1 with moderate to severe @entity195 , seven treated with @entity3393 (mean    SD age 77    8 years, mean    SD Mini-Mental State Examination [MMSE] score 16    5) and eight with placebo (mean    SD age 76    6 years, mean    SD MMSE score 13    1), were acquired at baseline (T0) and after 6 months of treatment (T6). Resting state components were extracted after spatial normalization in individual @entity1 with independent component analysis. The consistency of the components was assessed using ICASSO and the DMN was recognized through spatial correlation with a pre-defined template. Voxel-based statistical analyses were performed to study the change in DMN activity from T0 to T6 in the two groups. RESULTS: At T0, the two groups showed similar DMN activity except in the precuneus and cuneus, where the @entity1 who started treatment with @entity3393 had slightly greater activity (p < 0.05 corrected for familywise error [FWE]). The prospective comparison between T0 and T6 in the treated @entity1 showed increased DMN activation mapping in the precuneus (p < 0.05, FWE corrected), while the prospective comparison in the untreated @entity1 did not show significant changes. The treatment * time interaction term was significant at p < 0.05, FWE corrected. CONCLUSIONS: The results suggest a positive effect of @entity3393 treatment in @entity1 with moderate to severe @entity195 , resulting in an increased resting DMN activity in the precuneus region over 6 months. Future studies confirming the present findings are required to further demonstrate the beneficial effects of @entity3393 on the DMN in @entity195 .

title: Effect of XXXX on resting state default mode network activity in @entity195 .

answer: @entity3393 :: (MESH:D008559,Chemical) :: ['memantine']


abstract: OBJECTIVE: To determine the efficacy and factors affecting outcome of @entity6847 ( @entity6847 ) in @entity1 with severe @entity4810 . DESIGN: Prospectively designed clinical trial of @entity1 selected to participate in the study based upon the following inclusion criteria: previous total failed fertilization or unsuitable sperm parameters for conventional IVF. SETTING: Tertiary care academic center. @entity1 : Ninety-two consecutive couples undergoing IVF therapy augmented with @entity6847 during April through December 1994 were studied. MAIN OUTCOME MEASURES: Fertilization and ongoing implantation and pregnancy rates (PRs). RESULTS: A total of 1,163 preovulatory oocytes were manipulated, yielding a diploid fertilization rate of 60.9%; the oocyte damage rate was 13.2%. The transfer rate was 95% with 43.1% of cycles having excess embryos that were cryopreserved. Overall, the clinical and ongoing PRs per transfer were 31.9% and 26.8%, respectively. None of the sperm parameters of the original semen analysis correlated with @entity6847 outcome. Female age did not affect fertilization results but had a significant impact on PR (< 34 years: 48.9%; 35 to 39 years: 22.9%; > or = 40 years: 5.9% clinical PR per transfer). CONCLUSIONS: Intracytoplasmic sperm injection offers a new and powerful therapeutic option to treat couples with severe @entity4810 associated with a variety of @entity6847 . An adequate female age is a pivotal factor determining a successful outcome.

title: Intracytoplasmic sperm injection: achievement of high pregnancy rates in couples with severe XXXX is dependent primarily upon female and not male factors.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS']

entities_list: @entity6847 :: ('MESH:C567467', 'Disease') :: ['sperm abnormalities', 'intracytoplasmic sperm injection', 'ICSI']

entities_list: @entity4810 :: ('MESH:D007248', 'Disease') :: ['male factor infertility']

answer: @entity4810 :: (MESH:D007248,Disease) :: ['male factor infertility']


abstract: 1. Patterns of species @entity3794 often correlate strongly with measures of energy. The more individuals hypothesis (MIH) proposes that this relationship is facilitated by greater resources supporting larger populations, which are less likely to become extinct. Hence, the MIH predicts that community abundance and species @entity3794 will be positively related. 2. Recently, Buckley _ Jetz (2010, Journal of Animal Ecology, 79, 358-365) documented a decoupling of community abundance and species @entity497 in south-west United States, such that richer communities did not contain more individuals. They predicted, as a consequence of the mechanisms driving the decoupling, a more even distribution of species abundances in species-rich communities, evidenced by a positive relationship between species evenness and species @entity3794 . 3. We found a similar decoupling of the relationship between abundance and species @entity3794 for lizard communities in semi-arid south-eastern Australia. However, we note that a positive relationship between evenness and @entity3794 is expected because of the nature of the indices used. We illustrate this mathematically and empirically using data from both sets of lizard communities. When we used a measure of evenness, which is robust to species @entity3794 , there was no relationship between evenness and @entity3794 in either data set. 4. For lizard communities in both Australia and the United States, species dominance decreased as species @entity3794 increased. Further, with the iterative removal of the first, second and third most dominant species from each community, the relationship between abundance and species @entity3794 became increasingly more positive. 5. Our data support the contention that species @entity497 is not directly related to the number of individuals an environment can support. We propose an alternative hypothesis regarding how the decoupling of abundance and @entity3794 is accommodated; namely, an inverse relationship between species dominance and species @entity3794 , possibly because of ecological release.

title: The decoupling of abundance and species XXXX .

entities_list: @entity497 :: ('MESH:D003147', 'Disease') :: ['richness in lizard communities']

answer: @entity497 :: (MESH:D003147,Disease) :: ['richness in lizard communities']


abstract: 48 @entity1 with 50 involved limbs were retrospectively analyzed to determine factors influencing the outcome of surgical treatment for @entity7769 . All @entity1 were treated by anterior submuscular transposition of the ulnar nerve with Z-lengthening of the flexor-pronator origin. There were 24 @entity1 and 24 @entity1 with an average age of 42 years +/- 16.4 years (range, 5-75 years). The average follow-up time was 58 months (range, 12-156 months). A grading system was used pre- and post-operatively based on the severity of subjective complaints and objective findings. 92% of the @entity1 were satisfied, or satisfied with some reservations, and only 8% were dissatisfied. All @entity1 had either fair or poor pre-operative grades. 84% had excellent or good post-operative grades and only 16% had fair grades. There were no recurrences or poor post-operative grades in our series. Workers' compensation status had no statistically significant adverse effect on post-operative @entity1 satisfaction or post-operative grade. Anterior submuscular transposition of the ulnar nerve in this series provided satisfactory subjective outcome, relief of symptoms and adequate decompression of the ulnar nerve at the elbow.

title: Anterior submuscular transposition of the ulnar nerve for XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['women', 'patients', 'patient', 'men']

entities_list: @entity7769 :: ('MESH:D020430', 'Disease') :: ['cubital tunnel syndrome']

answer: @entity7769 :: (MESH:D020430,Disease) :: ['cubital tunnel syndrome']


abstract: In @entity958 , mutations in genes encoding ribosomal proteins (r-proteins) perturb various developmental processes. Whether these perturbations are caused by @entity1887 or partial dysfunction of the ribosome caused by deficiency of a particular ribosomal protein is not known. To distinguish these possibilities, a comparative study using several r-protein mutants was required. Here, we identified mutations in 11 r-protein genes from previously isolated denticulata and pointed-leaves mutants. Most of these mutations were associated with pointed leaves, with reduced growth due to a decrease in the number or size of palisade mesophyll and pavement cells. In addition, leaf abaxialization was usually observed when these r-protein mutations were combined with asymmetric leaves1 ( @entity6266 ) and @entity6267 mutations. These results suggest that the establishment of leaf polarity is highly sensitive to ribosome functionality in general. However, several r-protein mutants showed a preference towards a specific @entity245 . For example, rpl4d mutations did not affect cell proliferation but caused strong abaxialization of leaves in the @entity6266 and @entity6267 backgrounds. On the other hand, rps28b enhanced leaf abaxialization of @entity6267 to a weaker extent than expected on the basis of its negative effect on cell proliferation. In addition, hypomorphic @entity73209 alleles had the strongest effects on most of the phenotypes examined. These findings suggest that deficiencies in these three r-protein genes lead to production of dysfunctional ribosomes. Depending on their structural @entity66 may affect translation of specific transcripts involved in the regulation of some leaf developmental processes.

title: Differential contributions of ribosomal protein genes to XXXX leaf development.

entities_list: @entity66 :: ('MESH:D004194', 'Disease') :: ['abnormalities, dysfunctional ribosomes']

entities_list: @entity958 :: ('3702', 'Species') :: ['Arabidopsis thaliana']

entities_list: @entity1887 :: ('MESH:D000309', 'Disease') :: ['overall ribosome insufficiency']

entities_list: @entity245 :: ('MESH:D002658', 'Disease') :: ['developmental defect']

answer: @entity958 :: (3702,Species) :: ['Arabidopsis thaliana']


abstract: There are clones of @entity2800 cells which are different from normal myeloid cells in that they have become independent of @entity2772 for cell viability and growth. The ability of these clones to bind three types of hematopoietic growth factors (MGI-1GM = @entity2841 , @entity2772 = @entity2772 and MGI-1M = @entity6824 = @entity6824 ) was measured using the method of quantitative absorption at 1 degree C and low pH elution of cell-bound biological activity. Results of binding to normal myeloid and lymphoid cells were similar to those obtained by radioreceptor assays. The results indicate that the number of receptors on different clones of these leukemic cells varied from 0 to 1,300 per cell. The receptors have a high binding affinity. Receptors for different growth factors can be independently expressed in different clones. There was no relationship between expression of receptors for these growth factors and the phenotype of the leukemic cells regarding their ability to be induced to differentiate. The number of receptors on the leukemic cells was lower than on normal mature macrophages. Myeloid leukemic cells induced to differentiate by normal myeloid cell differentiation factor MGI-2 (= DF), or by low doses of @entity4316 or @entity2592 , showed an up-regulation of the number of MGI-1GM and @entity2772 receptors. Induction of differentiation of leukemic cells by MGI-2 also induced production and secretion of the growth factor MGI-1GM, and this induced MGI-1GM saturated the up-regulated MGI-1GM receptors. It is suggested that up-regulation of these receptors during differentiation is required for the functioning of differentiated cells.

title: Regulation of cell surface receptors for different hematopoietic growth factors on XXXX cells.

entities_list: @entity2800 :: ('MESH:D007951', 'Disease') :: ['myeloid leukemic']

entities_list: @entity4316 :: ('MESH:D003609', 'Chemical') :: ['actinomycin D']

entities_list: @entity2592 :: ('MESH:D003561', 'Chemical') :: ['cytosine arabinoside']

entities_list: @entity2772 :: ('3562', 'Gene') :: ['hematopoietic growth factor', 'IL-3', 'multi-CSF']

answer: @entity2800 :: (MESH:D007951,Disease) :: ['myeloid leukemic']


abstract: PURPOSE: An unusually high incidence of @entity5417 was observed during a phase I/II trial of high-dose intravenous @entity205 (CsA) therapy to @entity5 multidrug resistance (MDR). Five of 21 @entity1 experienced severe @entity5417 shortly after initiation of the first or second CsA infusion. We hypothesized that improper dissolution of the vehicle Cremophor EL may have been a cause for these @entity5417 . METHODS: All nurses who had administered intravenous @entity870 were interviewed regarding their technique of preparing the infusion and the occurrence of an anaphylactoid reaction. The responses were statistically analyzed. The effect of various mixing techniques on the distribution of Cremophor EL in the infusion was experimentally evaluated. Different mixing techniques were used to assess their effect on the distribution of Cremophor EL in the solution. RESULTS: Analysis of the preparation techniques of the CsA infusion showed significant correlation between suboptimal mixing of CsA by nurses and the occurrence of @entity5417 (P = .02). Experimental simulation showed that suboptimal mixing results in an uneven distribution of Cremophor EL, which subsequently sinks to the bottom of the vial. CONCLUSION: Improper mixing of high-dose CsA infusions causes nonsolubilized Cremophor EL to sink to the outflow area of the bottle. An initial bolus infusion of highly concentrated Cremophor EL may produce an anaphylactoid-like response. This mechanism of @entity137 is important to recognize, because it is easily preventable by proper preparation of the infusion, thus reducing the incidence of potentially life-threatening @entity5417 .

title: Anaphylactoid reactions in @entity1 receiving high-dose intravenous XXXX for reversal of @entity5 resistance: the causative role of improper dissolution of Cremophor EL.

entities_list: @entity1 :: ('9606', 'Species') :: ['children']

entities_list: @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['attenuate tumor']

entities_list: @entity205 :: ('MESH:D016572', 'Chemical') :: ['cyclosporine']

entities_list: @entity5417 :: ('MESH:D011695', 'Disease') :: ['anaphylactoid reactions']

answer: @entity205 :: (MESH:D016572,Chemical) :: ['cyclosporine']