abstract: BACKGROUND: Chronic @entity2371 is a common condition with a major impact on health-related quality of life, work productivity and health care utilisation. The cause of the @entity158 is not always obvious as no pathology is seen in 40-60% of the cases. In the absence of pathology there is no established treatment. The @entity1897 and parasympathetic ganglia in the uterosacral ligaments carry @entity158 from the uterus, cervix and other pelvic structures. Interruption of these nerve trunks by laparoscopic uterosacral nerve ablation (LUNA) may alleviate @entity158 . However, the balance of benefits and risks of this intervention have not been reliably assessed. LUNA has, nevertheless, been introduced into practice, although there remains controversy regarding indications for LUNA. Hence, there is an urgent need for a randomised controlled trial to confirm, or refute, any worthwhile effectiveness. The principal hypothesis is that, in @entity1 with chronic @entity2371 in whom diagnostic laparoscopy reveals either no pathology or mild @entity46 (AFS score </= 5) LUNA alleviates @entity158 and improves life quality at 12 months. METHODS/DESIGN: The principal objective is to test the hypothesis that in @entity1 with chronic @entity2371 in whom diagnostic laparoscopy reveals either no pathology or mild @entity46 (AFS score </= 5) LUNA alleviates @entity158 and improves life quality at 12 months. A multi-centre, prospective, randomised-controlled-trial will be carried out with blind assessment of outcomes in eligible consenting @entity1 randomised at diagnostic laparoscopy to LUNA (experimental group) or to no pelvic denervation (control group). Postal questionnaires including visual analogue scale for @entity158 (primary outcome), an index of sexual satisfaction and the EuroQoL 5D-EQ instrument (secondary outcomes) will be administered at 3, 6 and 12 months. The primary assessment of the effectiveness of LUNA will be from comparison of outcomes at the one-year follow-up, although the medium-term and longer-term risks and benefits of LUNA will also be evaluated.The sample size for this trial has been estimated as 420 @entity1 in total using the hypothesis that LUNA will alleviate @entity158 symptoms (i.e. reduce @entity158 scores on a VAS) more than no intervention at one-year following diagnostic laparoscopy and taking into consideration 20% loss to follow-up. The intention to treat analysis to address the principal research questions will be conducted using the one-year follow-up data.

title: A randomised controlled trial to assess the efficacy of Laparoscopic Uterosacral Nerve Ablation (LUNA) in the treatment of chronic XXXX : The trial protocol [ISRCTN41196151].

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

entities_list: @entity2371 :: ('MESH:D017699', 'Disease') :: ['pelvic pain']

entities_list: @entity1897 :: ('MESH:D010523', 'Disease') :: ['Lee-Frankenhauser sensory nerve plexuses']

entities_list: @entity46 :: ('MESH:D004715', 'Disease') :: ['endometriosis']

answer: @entity2371 :: (MESH:D017699,Disease) :: ['pelvic pain']


abstract: OBJECTIVE: To report on the long-term follow-up, clinically and serologically, of 98 @entity1 with @entity1252 treated with @entity1892 ( @entity1892 ) over a 12 year period, focusing on the duration of the depletion. METHODS: A retrospective review of clinical and serological features of all @entity1252 @entity1 treated with @entity1892 from January 2000 until December 2012 in the Centre for Rheumatology, University College London Hospital. Clinical activity was assessed by the classic BILAG score at baseline and 6 and 12 months after the treatment. RESULTS: The period of depletion is extremely variable between @entity1 and within the same @entity1 on different occasions. The @entity1 were divided into two groups according to the duration of depletion and a defined threshold of 12 months was utilized. The group with longer duration of depletion was associated with a better outcome, with a decrease in BILAG score at 6 and 12 months. This group was also associated with @entity2905 present at any time during the course of the @entity1 's disease. No other clinical or serological feature was associated with longer duration of @entity1892 . CONCLUSION: Cycles of @entity1892 that induce longer duration of @entity1892 are associated with better outcome. @entity2905 may help to predict longer duration of the depletion and better outcome, although the mechanism is unclear.

title: Longer duration of XXXX is associated with better outcome.

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

entities_list: @entity1892 :: ('MESH:D016393', 'Disease') :: ['B cell depletion', 'BCD']

entities_list: @entity2905 :: ('MESH:D008231', 'Disease') :: ['Lymphopenia', 'lymphopenia']

answer: @entity1892 :: (MESH:D016393,Disease) :: ['B cell depletion']


abstract: UNASSIGNED: Evidence for abnormal brain function as measured with diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) and @entity73 have been observed in inter-episode @entity162 ( @entity162 ) @entity1 . We aimed to create a joint statistical model of white matter integrity and functional response measures in explaining differences in working memory and processing speed among @entity162 @entity1 . Medicated inter-episode @entity162 (n=26; age=45.2  10.1 years) and healthy comparison (HC; n=36; age=46.3  11.5 years) @entity1 completed 51-direction DTI and fMRI while performing a working memory task. @entity1 also completed a processing speed test. Tract-based spatial statistics identified common white matter tracts where fractional anisotropy was calculated from atlas-defined regions of interest. Brain responses within regions of interest activation clusters were also calculated. Least angle regression was used to fuse fMRI and DTI data to select the best joint neuroimaging predictors of cognitive performance for each group. While there was overlap between groups in which regions were most related to cognitive performance, some relationships differed between groups. For working memory accuracy, @entity162 -specific predictors included bilateral dorsolateral prefrontal cortex from fMRI, splenium of the corpus callosum, left uncinate fasciculus, and bilateral superior longitudinal fasciculi from DTI. For processing speed, the genu and splenium of the corpus callosum and right superior @entity3057 from DTI were significant predictors of cognitive performance selectively for @entity162 @entity1 . @entity162 @entity1 demonstrated unique brain-cognition relationships compared to HC. These findings are a first step in discovering how interactions of structural and functional @entity75 contribute to @entity73 in @entity162 . (JINS, 2015, 21, 330-341).

title: Fusing Functional MRI and Diffusion Tensor Imaging Measures of Brain Function and Structure to Predict Working Memory and Processing Speed Performance among Inter-episode Bipolar XXXX .

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

entities_list: @entity162 :: ('MESH:D001714', 'Disease') :: ['bipolar disorder', 'BD']

entities_list: @entity75 :: ('MESH:D001927', 'Disease') :: ['brain abnormalities']

entities_list: @entity73 :: ('MESH:D003072', 'Disease') :: ['cognitive impairments', 'cognitive dysfunction']

entities_list: @entity3057 :: ('MESH:D017887', 'Disease') :: ['longitudinal fasciculus']

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


abstract: HYPOTHESIS: @entity0 are potentially malignant and are associated with a higher risk of @entity0 . DESIGN: Retrospective review of all pathological reports containing @entity0 (1983-2000) and review of selected specimens. SETTING: Tertiary, referral, university-affiliated medical center. @entity1 : Ninety-five @entity1 with a breast specimen containing a @entity1185 or @entity1185 . @entity1 with overt @entity1377 without @entity1185 were excluded. INTERVENTION: All histopathological characteristics of the @entity1185 and the surrounding tissue were noted. The incidence of malignant and other proliferative histopathological findings were analyzed, comparing solitary @entity513 cases to @entity1185 cases. The Fisher exact test and chi2 test were applied for statistical analysis. MAIN OUTCOME MEASURES: Surgical @entity513 should include margins wide enough to secure removal of any proliferative tissue within or around the @entity1185 and to enable thorough evaluation of the risk for future @entity0 . RESULTS: @entity1185 were associated with @entity0 in 7 @entity1 (10%) in this series. An additional 9% (n = 6) presented with invasive or noninvasive @entity189 . @entity1185 was noted in 6% of @entity1 (n = 4). The risk of associated @entity5 was not significantly different between solitary @entity513 and @entity1185 . CONCLUSION: Increased risk of @entity0 is associated with all forms of @entity1185 .

title: Are solitary XXXX entirely benign?

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

entities_list: @entity1377 :: ('MESH:D002291', 'Disease') :: ['papillary carcinoma']

entities_list: @entity0 :: ('MESH:D001943', 'Disease') :: ['breast carcinoma', 'breast cancer', 'Solitary breast papillomas', 'breast papilloma']

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

entities_list: @entity1185 :: ('MESH:D010212', 'Disease') :: ['Atypical papilloma', 'papillomatosis', 'multiple papilloma', 'Solitary papillomas', 'papilloma']

entities_list: @entity189 :: ('MESH:D002277', 'Disease') :: ['carcinoma within the papilloma']

entities_list: @entity513 :: ('MESH:D044584', 'Disease') :: ['ductal papilloma', 'removal of solitary ductal papillomas']

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


abstract: OBJECTIVE: To evaluate the effectiveness of more than 12 months of oral @entity1033 therapy in reducing recurrences of @entity1034 . METHODS: We retrospectively compared @entity1034 recurrence in 2 groups of @entity1 . In group 1, @entity1 used oral @entity1033 for at least 12 months and then discontinued the treatment. In group 2, @entity1 received the treatment for at least 18 months. We compared recurrences when both groups were using @entity1033 (period 1) and when only group 2 was receiving the drug ( @entity5394 ). Statistical analysis was performed with the t test, chi2 test, and Kaplan-Meier method. RESULTS: Group 1 had 18 @entity1 and a mean +/- SD follow-up of 45.2 +/- 22.2 months. Group 2 had 22 @entity1 and a mean +/- SD follow-up of 42.4 +/- 30.2 months. Six @entity1 (33%) in group 1 and 4 @entity1 (18%) in group 2 had recurrence in period 1 (P =.3). In @entity5394 , 14 @entity1 (78%) in group 1 and 8 @entity1 (36%) in group 2 had recurrence (P =.01). Mean +/- SD recurrence-free survival in @entity5394 was 15.3 +/- 5.5 months in group 1 and 37.3 +/- 6.3 months in group 2 (P =.001). CONCLUSIONS: Long-term oral @entity1033 use seems to remain effective in decreasing the number of @entity1034 recurrences beyond 12 months.

title: Long-term XXXX use to prevent recurrent ocular herpes simplex virus infection.

entities_list: @entity1033 :: ('MESH:D000212', 'Chemical') :: ['acyclovir']

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

entities_list: @entity1034 :: ('MESH:D016849', 'Disease') :: ['ocular herpes simplex virus']

answer: @entity1033 :: (MESH:D000212,Chemical) :: ['acyclovir']


abstract: 1. Plasma concentrations of endothelin are increased in @entity1 with @entity96 as well as in @entity1 with liver @entity3 . However, the impact of these findings remains uncertain. 2. We thus analyzed the endothelin system in a @entity35 @entity157 model ( @entity7283 7777) in vitro and in vivo. 3. Our study revealed that tissue concentrations of @entity2232 ( @entity2232 ) and big- @entity2232 , the precursor of @entity2232 , were significantly elevated in @entity7283 7777 as compared to normal liver. The ETA receptor density was significantly elevated, whereas the density of the ETB receptor was @entity7283 7777. 4. We could also demonstrate that @entity157 cells secrete @entity2232 . 5. Exogenously added @entity2232 enhances @entity157 cell growth in a dose-dependent manner. Endothelin receptor antagonists (ETA and combined ETA/ETB receptor antagonists) inhibit @entity5 cell growth in vitro. Since the combined ETA/ETB receptor antagonist was more effective in vitro, we used this compound also for in vivo studies and could demonstrate that a combined ETA/ETB receptor antagonist is able to reduce @entity157 growth in vivo. 6. In conclusion, the endothelin system is activated in @entity7283 7777 and contributes to @entity157 growth. Since endothelin receptor antagonists are well-tolerated upcoming clinically used drugs without major side effects, our data might provide a new pharmacological approach to reduce @entity157 growth in vivo.

title: The endothelin system in XXXX -7777: an endothelin receptor antagonist inhibits growth in vitro and in vivo.

entities_list: @entity96 :: ('MESH:D008113', 'Disease') :: ['hepatocellular cancer']

entities_list: @entity7283 :: ('MESH:D008114', 'Disease') :: ['Morris hepatoma', 'decreased in Morris hepatoma']

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

entities_list: @entity157 :: ('MESH:D006528', 'Disease') :: ['hepatoma']

answer: @entity7283 :: (MESH:D008114,Disease) :: ['Morris hepatoma']


abstract: UNASSIGNED: OBJECTIVE To use whole genome sequencing to describe the likely origin of an outbreak of @entity796 in a neonatal unit. DESIGN Outbreak investigation. SETTING The neonatal intensive care unit service of a major obstetric tertiary referral center. @entity1 @entity1 admitted to the neonatal unit who developed @entity796 colonization or @entity281 . METHODS We undertook whole genome sequencing of @entity796 strains isolated from colonized @entity1 and from the neonatal unit environment. RESULTS Eighteen @entity1 were colonized with @entity796 . Isolates from 12 @entity1 and 7 environmental samples were sequenced. All but one of the clinical isolates clustered in ST253 and no differences were detected between unmapped reads. The environmental isolates revealed a variety of sequence types, indicating a large diverse bioburden within the unit, which was subsequently confirmed via enterobacterial repetitive intergenic consensus         polymerase chain reaction typing of post-outbreak isolates. One environmental isolate, obtained from a sink in the unit, clustered within ST253 and differed from the outbreak strain by 9 single-nucleotide polymorphisms only. This information allowed us to focus @entity281 control activities on this sink. CONCLUSIONS Whole genome sequencing can provide detailed information in a clinically relevant time frame to aid management of outbreaks in critical @entity1 management areas. The superior discriminatory power of this method makes it a powerful tool in @entity281 control. Infect Control Hosp Epidemiol 2015;00(0):1         7.

title: Whole Genome Sequencing in Real-Time Investigation and Management of a XXXX Outbreak on a Neonatal Intensive Care Unit.

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

entities_list: @entity281 :: ('MESH:D007239', 'Disease') :: ['infection']

entities_list: @entity796 :: ('287', 'Species') :: ['Pseudomonas aeruginosa', 'P. aeruginosa']

answer: @entity796 :: (287,Species) :: ['Pseudomonas aeruginosa']


abstract: PURPOSE: To determine the expression of @entity33238 and the localization of @entity6930 and @entity11018 during the early stages of corneal wound healing in @entity35 . METHODS. One eye each of 30 adult @entity35 was treated with excimer laser keratectomy; the other eye was untreated. Frozen sections of corneas obtained 6, 18, and 24 hours and 3 and 7 days after wounding were used to perform immunoconfocal microscopy and in situ hybridization. RESULTS: @entity6929 was immunolocalized to the basement membrane zone and superficial stroma, and its mRNA was exclusively localized to basal epithelial cells migrating across the wound at 18 and 24 hours and 3 days after wounding. @entity6930 was also immunolocalized to the basement membrane zone and superficial stroma at the same time points. @entity11017 was immunolocalized to the epithelium and stroma of normal corneas and was predominant in the basal epithelium and superficial stroma at 3 and 7 days after wounding. In situ hybridization confirmed @entity11017 expression by the epithelial cells and the stromal keratocytes. Tissue inhibitor of metalloproteinase-2 was immunolocalized to the epithelium in normal and wounded corneas. Intense @entity11018 labeling of the basement membrane zone was noted 3 days after wounding. CONCLUSIONS: Unlike @entity11017 , @entity6929 is expressed exclusively by migrating basal epithelial cells after wounding. The matrix metalloproteinase-tissue inhibitor of metalloproteinase (MMP)/ @entity6930 systems may play an important role in the early stages of corneal wound healing after excimer laser keratectomy.

title: Expression of XXXX , and TIMPs 1 and 2 during corneal wound healing.

entities_list: @entity6930 :: ('116510(Tax:10116)', 'Gene') :: ['TIMP', 'Tissue inhibitor of metalloproteinase-1', 'tissue inhibitors of metalloproteinase (TIMP)-1']

entities_list: @entity35 :: ('10116', 'Species') :: ['Sprague-Dawley rats', 'rats']

answer: @entity33238 :: (81686;81687,Gene) :: ['gelatinases A and B']


abstract: Proteolytic cleavage of the extracellular domain of the type II IL-1 decoy receptor ( @entity10732 ) generates soluble IL-1-binding proteins that prevent excessive bioactivity by binding free IL-1. In this study we report that an @entity2965 , @entity8460 ( @entity8460 ), is required for @entity10732 shedding. Coimmunoprecipitation experiments demonstrate an association between endogenous membrane-associated @entity8460 and a 47-kDa @entity10732 , consistent with ectodomain cleavage of the membrane-bound receptor. A direct correlation exists between @entity8460 protein expression and @entity10732 shedding, as cell lines overexpressing @entity8460 have increased @entity10732 shedding and decreased membrane-associated @entity10732 . Basal @entity10732 shedding is absent from @entity8460 knockout cell lines, demonstrating that @entity8460 is required for constitutive @entity10732 shedding. Similarly, @entity4515 -mediated @entity10732 shedding is almost entirely @entity8460 -dependent. @entity8460 expression also enhances @entity1360 -induced @entity10732 shedding. @entity8460 did not alter levels of membrane-associated IL-1RI or @entity10496 antagonist release from @entity8460 cell lines, which suggests that the ability of @entity8460 to promote shedding of @entity10496 family members may be specific for @entity10732 . Further, increased @entity10732 shedding by @entity8460 -overexpressing cells attenuates the biological activity of @entity1356 . We conclude that the ability of @entity8460 to enhance @entity10732 shedding represents a new mechanism by which IL-1-induced cellular events can be modulated. As @entity8460 also promotes the shedding of the structurally unrelated 55-kDa, type I TNF receptor and the @entity10497 , we propose that @entity8460 may play an important role in regulating innate immune and inflammatory responses by increasing cytokine receptor shedding.

title: Shedding of the type II IL-1 decoy receptor requires a multifunctional XXXX , @entity2965 regulator of TNF receptor type 1 shedding.

entities_list: @entity8460 :: ('51752', 'Gene') :: ['ARTS-1', 'aminopeptidase regulator of TNFR1 shedding']

entities_list: @entity1360 :: ('MESH:D015759', 'Chemical') :: ['ionomycin']

answer: @entity2965 :: (10404,Gene) :: ['aminopeptidase']


abstract: Proteolytic cleavage of the extracellular domain of the type II IL-1 decoy receptor ( @entity10732 ) generates soluble IL-1-binding proteins that prevent excessive bioactivity by binding free IL-1. In this study we report that an @entity2965 , @entity8460 ( @entity8460 ), is required for @entity10732 shedding. Coimmunoprecipitation experiments demonstrate an association between endogenous membrane-associated @entity8460 and a 47-kDa @entity10732 , consistent with ectodomain cleavage of the membrane-bound receptor. A direct correlation exists between @entity8460 protein expression and @entity10732 shedding, as cell lines overexpressing @entity8460 have increased @entity10732 shedding and decreased membrane-associated @entity10732 . Basal @entity10732 shedding is absent from @entity8460 knockout cell lines, demonstrating that @entity8460 is required for constitutive @entity10732 shedding. Similarly, @entity4515 -mediated @entity10732 shedding is almost entirely @entity8460 -dependent. @entity8460 expression also enhances @entity1360 -induced @entity10732 shedding. @entity8460 did not alter levels of membrane-associated IL-1RI or @entity10496 antagonist release from @entity8460 cell lines, which suggests that the ability of @entity8460 to promote shedding of @entity10496 family members may be specific for @entity10732 . Further, increased @entity10732 shedding by @entity8460 -overexpressing cells attenuates the biological activity of @entity1356 . We conclude that the ability of @entity8460 to enhance @entity10732 shedding represents a new mechanism by which IL-1-induced cellular events can be modulated. As @entity8460 also promotes the shedding of the structurally unrelated 55-kDa, type I TNF receptor and the @entity10497 , we propose that @entity8460 may play an important role in regulating innate immune and inflammatory responses by increasing cytokine receptor shedding.

title: Shedding of the type II IL-1 decoy receptor requires a multifunctional @entity2965 , XXXX regulator of TNF receptor type 1 shedding.

answer: @entity2965 :: (10404,Gene) :: ['aminopeptidase']


abstract: OPINION STATEMENT: The addition of targeted therapy to a 5-FU chemotherapy backbone is now a standard of care in metastatic @entity14 . @entity470 ( @entity470 ) inhibitors have been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in the first line for @entity1 with @entity5 that do not harbor @entity984 exon 2 mutations. Eligibility criteria for most clinical trials involving @entity470 inhibitors in recent years have used the absence of @entity984 exon 2 mutation as the sole criteria for entry, as this specific mutation has been consistently shown to be predictive of a poor response to @entity470 inhibitors. However, expanded analyses of first-line metastatic trials reveal that other RAS mutations, such as other @entity984 mutations in exons 3 and 4, along with @entity8497 mutations, are predictive of poor responses to @entity470 inhibitors as well. Testing for a full panel of these RAS mutations should be done prior to initiating treatment with an @entity470 inhibitor. Further clinical trials are required to determine the predictive impact of each of these individual mutations. To date, they have been analyzed in the aggregate. The addition of targeted therapy, bevacizumab or an @entity470 inhibitor, to a chemotherapy backbone should be considered for all appropriate @entity1 . The relevant clinical trials that evaluated @entity1 without any RAS mutation and compared an @entity470 inhibitor to chemotherapy alone show a distinct advantage in overall survival and progression-free survival to the groups that received @entity470 inhibition. The largest trial that compared bevacizumab with an @entity470 inhibitor in the first line, CALGB/SWOG 80405, did not show a statistically significant difference between the two groups, making the use of bevacizumab, cetuximab, or panitumumab reasonable in the first line.

title: RAS Mutations Beyond XXXX Exon 2: A Review and Discussion of Clinical Trial Data.

entities_list: @entity470 :: ('1956', 'Gene') :: ['Epidermal growth factor receptor', 'EGFR']

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

entities_list: @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer']

answer: @entity984 :: (3845,Gene) :: ['KRAS']


abstract: OBJECTIVE: To assess the reliability of strength testing techniques among centers investigating @entity1 with @entity746 . METHODS: The authors compared test reliability in manual muscle testing ( @entity569 ) and maximal voluntary isometric contraction (MVIC) scores among institutions and test validity by comparing change over time between @entity569 and MVIC. The authors examined 63 subjects at 3-month intervals for 12 months. At enrollment and at 6 months, two physical therapists each examined the subjects twice. @entity569 scores were calculated as modifications of the Medical Research Council scale. MVIC scores were generated as standardized megascores. Intraclass correlation coefficients and coefficients of variation compared reproducibility, and Pearson correlation coefficients compared change over time. The power of each measure to detect disease progression over time was assessed by estimating coefficients of variation for the average change. RESULTS: Reproducibility between MVIC and @entity569 was equivalent. Sensitivity to detect progressive weakness and power to detect this change, however, favored @entity569 , an effect largely accounted for by the number of muscles sampled. CONCLUSIONS: In multicentered trials, uniformly trained physical therapists reproducibly and accurately measure strength by both @entity569 and MVIC. The authors found @entity569 to be the preferred measure of global strength because of its better Pearson correlation coefficients, essentially equivalent reproducibility, and more favorable coefficient of variation.

title: A comparison of muscle strength testing techniques in XXXX .

entities_list: @entity746 :: ('MESH:D000690', 'Disease') :: ['amyotrophic lateral sclerosis']

answer: @entity746 :: (MESH:D000690,Disease) :: ['amyotrophic lateral sclerosis']


abstract: Several cytokines and growth factors modulate angiogenesis through a fine tuned paracrine or autocrine mode of action. Among them is plateled-derived endothelial cell growth factor ( @entity1015 ), which is highly is expressed in @entity5 , and is angiogenic by stimulation of endothelial cell migration. Studies have shown that @entity1015 is identical to the well known enzyme @entity1014 phosphorylase (TP), which is involved in @entity1014 metabolism and homeostasis. Interestingly, @entity1015 plays an angiogenic role as a result of its TP enzyme activity. In light of these findings, @entity1015 /TP should not be considered a true growth factor, and its @entity1015 name is now actually a misnomer. Recently, TP activity was thought of as an interesting potential two-face target for controling @entity5 -dependent angiogenesis. In fact, on one hand, its high levels of expression in @entity5 compared to non-neoplastic regions, and its broad substrate specificity suggested that TP could be used as an enzymatic tool to locally activate anticancer @entity2353 bases or base analogs. On the other hand, its enzyme-dependent angiogenic activity engendered the search for specific inhibitors to reduce TP-dependent angiogenesis. This review will describe TP, its activity, its possible mechanisms of action and its role in angiogenesis. Particular attention will be focused on the design and biological characterization of novel TP inhibitors which recently showed promising anticancer activity.

title: XXXX phosphorylase: a two-face Janus in anticancer chemotherapy.

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

entities_list: @entity2353 :: ('CHEBI:33838', 'Chemical') :: ['nucleoside']

entities_list: @entity1014 :: ('MESH:D013936', 'Chemical') :: ['thymidine']

answer: @entity1014 :: (MESH:D013936,Chemical) :: ['Thymidine']


abstract: INTRODUCTION: @entity1737 is a localized form of @entity1737 in which only the extra-ocular muscles are clinically affected, namely the levator palpebrae superioris and orbicularis oculi. Two years after onset of the @entity2788 , it became generalized in 44-53% of the @entity1 . OBJECTIVE: 1. To describe the clinical features, diagnostic characteristics and clinical course of seven @entity1 who fulfilled the criteria for diagnosis of @entity1737 and in whom the condition did not become generalized: 2. Review recent papers on this. Material and methods. We studied seven @entity1 (two @entity1 and two @entity1 ) diagnosed as having @entity1737 , and followed them up for at least three years. RESULTS: The average age was 56.5. The clinical findings were of ptosis of the eyelids and @entity892 . All seven @entity1 were treated with @entity4836 . In six cases prednisone was also given and in one @entity1 thymectomy was done. There was a satisfactory result in all cases. CONCLUSIONS: The basic treatment of @entity1737 is with anticholinesterases and @entity288 . Occasionally other immunosuppressives may be required. @entity229 seems to reduce the number of @entity1 who go on to develop the generalized form.

title: [ XXXX : clinical course and strategies for treatment].

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

entities_list: @entity229 :: ('MESH:D011241', 'Chemical') :: ['Prednisone']

entities_list: @entity4836 :: ('MESH:D011729', 'Chemical') :: ['pyridostigmine']

entities_list: @entity1737 :: ('MESH:D009157', 'Disease') :: ['Ocular myasthenia gravis', 'myasthenia', 'ocular myasthenia gravis', 'ocular myasthenia']

entities_list: @entity2788 :: ('MESH:D015785', 'Disease') :: ['ocular condition']

entities_list: @entity892 :: ('MESH:D004172', 'Disease') :: ['diplopia']

entities_list: @entity288 :: ('MESH:D000305', 'Chemical') :: ['corticosteroids']

answer: @entity1737 :: (MESH:D009157,Disease) :: ['Ocular myasthenia']


abstract: OBJECTIVE: In an animal model, we tested the hypothesis that intracerebral, extracellular @entity1063 (NE) influences cerebral blood flow (CBF) in the presence of @entity7026 ( @entity2758 ). METHODS: A microdialysis (MD) probe was implanted into the cortices of @entity35 3 months after the creation of extracranial arteriovenous fistulae (AVFs; n = 19), carotid ligation (n = 10), and cervical vessel preparation (sham operations; n = 8). Ipsilateral regional cortical @entity26 saturation (microspectrophotometry) and regional cerebral blood flow (laser Doppler flowmetry) were scanned with simultaneous MD sampling for NE (high-performance liquid chromatography). Local CBF and cortical capillary @entity26 saturation (SO2) were recorded continuously with serial MD sampling after @entity432 for 100 minutes. The scanning protocol was repeated after 120 minutes. Values were compared by analysis of variance and Duncan's test (P < 0.05; values expressed as mean +/- standard deviation). RESULTS: NE was highest in sham-operated animals and lowest after carotid ligation as compared with before and after the creation of the AVFs (sham operations, 5.9 +/- 2.3 nmol/L; common carotid artery ligation, 2.4 +/- 1 nmol/L; before creation of AVF, 4.1 +/- 1.9 nmol/L; after creation of AVF, 4.1 +/- 2.3 nmol/L). Regional cortical @entity26 saturation differed significantly between all groups; regional cerebral blood flow was lower only in sham-operated animals (sham operations, 210 +/- 75 laser Doppler units [LDU], 71 +/- 13% SO2; common carotid artery ligation, 250 +/- 82 LDU, 62 +/- 19% SO2; before creation of AVF, 249 +/- 96 LDU, 65 +/- 14% SO2; after creation of AVF, 256 +/- 82 LDU, 74 +/- 10% SO2). After @entity432 , a sustained CBF increase for 100 minutes up to 40% above baseline (i.e., regional cerebral blood flow and regional cortical @entity26 saturation before occlusion) was observed. SO2 increased to 16% after 120 minutes. Peaks of NE concentrations occurred 40 minutes and 100 minutes after @entity432 . CONCLUSION: The model seems to be valid for the simulation of events that occur before and after the obliteration of @entity1 cerebral @entity2758 in most cases, but not in those prone to hyperperfusion syndromes. The results provide evidence that cerebral sympathetic nervous system activity can be monitored by in vivo MD and that NE may play a role in CBF control before and after the obliteration of AVFs.

title: XXXX in the @entity35 cortex before and after occlusion of chronic arteriovenous fistulae: a microdialysis study in an animal model of @entity7026 .

entities_list: @entity7026 :: ('MESH:D002538', 'Disease') :: ['cerebral arteriovenous malformations']

entities_list: @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen']

entities_list: @entity432 :: ('MESH:D001157', 'Disease') :: ['fistula occlusion']

entities_list: @entity35 :: ('10116', 'Species') :: ['Sprague-Dawley rats']

entities_list: @entity1063 :: ('MESH:D009638', 'Chemical') :: ['norepinephrine']

answer: @entity1063 :: (MESH:D009638,Chemical) :: ['Norepinephrine']


abstract: OBJECTIVE: In an animal model, we tested the hypothesis that intracerebral, extracellular @entity1063 (NE) influences cerebral blood flow (CBF) in the presence of @entity7026 ( @entity2758 ). METHODS: A microdialysis (MD) probe was implanted into the cortices of @entity35 3 months after the creation of extracranial arteriovenous fistulae (AVFs; n = 19), carotid ligation (n = 10), and cervical vessel preparation (sham operations; n = 8). Ipsilateral regional cortical @entity26 saturation (microspectrophotometry) and regional cerebral blood flow (laser Doppler flowmetry) were scanned with simultaneous MD sampling for NE (high-performance liquid chromatography). Local CBF and cortical capillary @entity26 saturation (SO2) were recorded continuously with serial MD sampling after @entity432 for 100 minutes. The scanning protocol was repeated after 120 minutes. Values were compared by analysis of variance and Duncan's test (P < 0.05; values expressed as mean +/- standard deviation). RESULTS: NE was highest in sham-operated animals and lowest after carotid ligation as compared with before and after the creation of the AVFs (sham operations, 5.9 +/- 2.3 nmol/L; common carotid artery ligation, 2.4 +/- 1 nmol/L; before creation of AVF, 4.1 +/- 1.9 nmol/L; after creation of AVF, 4.1 +/- 2.3 nmol/L). Regional cortical @entity26 saturation differed significantly between all groups; regional cerebral blood flow was lower only in sham-operated animals (sham operations, 210 +/- 75 laser Doppler units [LDU], 71 +/- 13% SO2; common carotid artery ligation, 250 +/- 82 LDU, 62 +/- 19% SO2; before creation of AVF, 249 +/- 96 LDU, 65 +/- 14% SO2; after creation of AVF, 256 +/- 82 LDU, 74 +/- 10% SO2). After @entity432 , a sustained CBF increase for 100 minutes up to 40% above baseline (i.e., regional cerebral blood flow and regional cortical @entity26 saturation before occlusion) was observed. SO2 increased to 16% after 120 minutes. Peaks of NE concentrations occurred 40 minutes and 100 minutes after @entity432 . CONCLUSION: The model seems to be valid for the simulation of events that occur before and after the obliteration of @entity1 cerebral @entity2758 in most cases, but not in those prone to hyperperfusion syndromes. The results provide evidence that cerebral sympathetic nervous system activity can be monitored by in vivo MD and that NE may play a role in CBF control before and after the obliteration of AVFs.

title: @entity1063 in the @entity35 cortex before and after occlusion of chronic arteriovenous fistulae: a microdialysis study in an animal model of XXXX .

answer: @entity7026 :: (MESH:D002538,Disease) :: ['cerebral arteriovenous malformations']


abstract: OBJECTIVE: In an animal model, we tested the hypothesis that intracerebral, extracellular @entity1063 (NE) influences cerebral blood flow (CBF) in the presence of @entity7026 ( @entity2758 ). METHODS: A microdialysis (MD) probe was implanted into the cortices of @entity35 3 months after the creation of extracranial arteriovenous fistulae (AVFs; n = 19), carotid ligation (n = 10), and cervical vessel preparation (sham operations; n = 8). Ipsilateral regional cortical @entity26 saturation (microspectrophotometry) and regional cerebral blood flow (laser Doppler flowmetry) were scanned with simultaneous MD sampling for NE (high-performance liquid chromatography). Local CBF and cortical capillary @entity26 saturation (SO2) were recorded continuously with serial MD sampling after @entity432 for 100 minutes. The scanning protocol was repeated after 120 minutes. Values were compared by analysis of variance and Duncan's test (P < 0.05; values expressed as mean +/- standard deviation). RESULTS: NE was highest in sham-operated animals and lowest after carotid ligation as compared with before and after the creation of the AVFs (sham operations, 5.9 +/- 2.3 nmol/L; common carotid artery ligation, 2.4 +/- 1 nmol/L; before creation of AVF, 4.1 +/- 1.9 nmol/L; after creation of AVF, 4.1 +/- 2.3 nmol/L). Regional cortical @entity26 saturation differed significantly between all groups; regional cerebral blood flow was lower only in sham-operated animals (sham operations, 210 +/- 75 laser Doppler units [LDU], 71 +/- 13% SO2; common carotid artery ligation, 250 +/- 82 LDU, 62 +/- 19% SO2; before creation of AVF, 249 +/- 96 LDU, 65 +/- 14% SO2; after creation of AVF, 256 +/- 82 LDU, 74 +/- 10% SO2). After @entity432 , a sustained CBF increase for 100 minutes up to 40% above baseline (i.e., regional cerebral blood flow and regional cortical @entity26 saturation before occlusion) was observed. SO2 increased to 16% after 120 minutes. Peaks of NE concentrations occurred 40 minutes and 100 minutes after @entity432 . CONCLUSION: The model seems to be valid for the simulation of events that occur before and after the obliteration of @entity1 cerebral @entity2758 in most cases, but not in those prone to hyperperfusion syndromes. The results provide evidence that cerebral sympathetic nervous system activity can be monitored by in vivo MD and that NE may play a role in CBF control before and after the obliteration of AVFs.

title: @entity1063 in the XXXX cortex before and after occlusion of chronic arteriovenous fistulae: a microdialysis study in an animal model of @entity7026 .

answer: @entity35 :: (10116,Species) :: ['rat']


abstract: A study about the frequency of respiratory and @entity56 in childhood was carried out in Rome, during the 2000-2001 school year. This survey represents the Italian contribution to the second phase of the International Study on Asthma and @entity566 in Childhood (ISAAC Phase Two). A properly filled in ISAAC Phase II questionnaire was returned by parents of 1,760 @entity1 attending the fifth grade in primary school (83.5% of the target). Prick tests were performed to provide an objective measure of atopy, defined as skin reactivity to one or more allergens. The presence of visible @entity1909 was determined through skin examination. Lifetime prevalence for @entity565 , @entity2023 and @entity484 was 12.4%, 13.2% and 15.1%, respectively. Period prevalence in the last 12 months was 7.0% for attacks of wheezing or whistling in the chest, 9.1% for @entity2490 symptoms, and 9.5% for @entity1909 . A total of 1.6% of the @entity1 under examination had a visible @entity1909 . Of the @entity1 who performed prick test, 31.8% was skin positive at least to one of the adopted allergens. An international comparison with the results of other ISAAC Phase Two studies (conducted in Albania, Germany, Hong Kong, UK and Sweden) has shown that Rome and Hong Kong were the areas with the highest prevalence rate for atopy, but had comparatively low proportions of @entity748 subjects. This inconsistency suggests that factors other than atopy could be responsible for the geographic epidemiological distribution of @entity565 .

title: [Asthma and XXXX in childhood in Rome: Italian contribution to the ISAAC II].

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

entities_list: @entity748 :: ('MESH:D013224', 'Disease') :: ['asthmatic']

entities_list: @entity2023 :: ('MESH:D006255', 'Disease') :: ['allergic rhinitis']

entities_list: @entity566 :: ('MESH:D006967', 'Disease') :: ['Allergies']

entities_list: @entity56 :: ('MESH:D004342', 'Disease') :: ['allergic disorders']

entities_list: @entity1909 :: ('MESH:D003872', 'Disease') :: ['dermatitis symptoms', 'flexural dermatitis']

answer: @entity566 :: (MESH:D006967,Disease) :: ['allergies']


abstract: The opening of the new Malpensa 2000 Airport worried @entity1 living in the neighbouring towns about possible effects of acoustic and air pollution on health status. For this reason, Varese Health Unit set up a study involving housewives and General Practitioners. This study has been carried out in 3 Areas: A Area, bordering the airport, B Area, at intermediate distance, and C Area, at long distance. On the whole, 932 housewives (18 to 64 years old) and 92 General Practitioners, were involved. The questionnaire, distributed to housewives between @entity4456 st and November 30th 2000, was filled out in the doctor's surgery who furthermore added clinical data. Chi-square statistics were calculated to test the association between living area and personal data, behavioural and environmental characteristics, and @entity74 . To describe possible interrelationships between living Area and the answers supplied by housewives and General Practitioners the multiple correspondence multivariate analysis technique was applied. The housewives living next to the airport (A area) frequently report insomnia, nocturnal waking, @entity148 and @entity393 . The multivariate analysis has shown a relationship between recently increasing noise noted by the housewives, and the area where they live, as well as a noticeable coherence between the answers given by the housewives and those given by the General Practitioners, who reported higher frequencies of cephalgy, @entity566 , @entity148 , medical consultation, @entity1245 's and sleeping @entity74 in A Area compared to C Area. The airport's presence seems to be associated with the onset of @entity392 in neighbouring population. Some of these disorders, in particular neuropsychological ones, are clinically confirmed by General Practitioners, and are consistent with different noise exposure levels.

title: [Epidemiologic study Salus domestica: evaluation of health damage in a sample of XXXX living near the Malpensa 2000 airport].

entities_list: @entity566 :: ('MESH:D006967', 'Disease') :: ['allergies']

entities_list: @entity1245 :: ('MESH:D001569', 'Chemical') :: ['benzodiazepine']

entities_list: @entity148 :: ('MESH:D001008', 'Disease') :: ['anxiety', 'anxiety neurosis']

entities_list: @entity74 :: ('MESH:D030342', 'Disease') :: ["disorder's prescriptions", 'reported disorders']

entities_list: @entity392 :: ('MESH:D014012', 'Disease') :: ['subjective disorders']

entities_list: @entity393 :: ('MESH:D034381', 'Disease') :: ['difficulty in hearing words']

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


abstract: The establishment of "best clinical practices" founded upon evidence-based medicine has become an increasingly important priority. Frequently, management guidelines are derived from published research data and disseminated among practitioners to help optimize @entity1 care. The ultimate clinical impact of these guidelines in the "real world," however, is often clouded by an incomplete assessment of @entity1 outcomes throughout the continuum of health-care delivery models. In order to address this gap in clinical outcome assessment, we propose to establish the Connecticut Cardiovascular Consortium. The Consortium will consist of a collaborative partnership among all 31 Connecticut hospitals working in concert with Connecticut Office of Health Care Access (OHCA). The primary objective of the Consortium will be to assess, compare, and optimize clinical outcomes among Connecticut residents with @entity65 . As an initial goal for the Consortium, we further propose to undertake a prospective, observational study of Connecticut residents who present with @entity583 ( @entity583 ). Recent advances in pharmacologic and mechanical reperfusion for @entity583 have resulted in a need to define the optimal use of these therapies in the community at large. The primary purpose of this study will be to determine the relative merits of different treatment patterns for @entity583 with regard to the use of fibrinolytic therapy and percutaneous coronary intervention (PCI). Particular emphasis will be placed on assessing the relative benefits of urgent mechanical revascularization performed at the state's seven tertiary facilities with PCI capability compared to all other treatment modalities. Successful completion of this unique collaborative endeavor is expected to have significant impact on improved @entity1 care and on current health-care policy for medical resource allocation. Moreover, continued collaboration of health-care providers within the Connecticut Cardiovascular Consortium infrastructure should serve as a useful mechanism for ongoing improvements in evidence-based cardiovascular medicine and clinical research in the state of Connecticut.

title: The Connecticut Cardiovascular Consortium: a unique, state-wide research collaboration to advance clinical outcomes in XXXX with heart disease.

entities_list: @entity583 :: ('MESH:D009203', 'Disease') :: ['ST Segment Elevation Acute Myocardial Infarction', 'STEMI']

entities_list: @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular disease']

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


abstract: BACKGROUND: @entity10420 ( @entity10420 ) and @entity4225 ( @entity4225 ) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. METHOD: DSM-IV criteria for @entity10420 and @entity4225 were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. RESULTS: The mean criterion count for @entity10420 and @entity4225 decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for @entity10420 and 0.45 for @entity4225 . The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by @entity10420 and @entity4225 , and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to @entity10420 and @entity4225 . Genetic effects accounted for 71% and 72% of the stability over time for @entity10420 and @entity4225 , respectively. The genetic and environmental correlations between @entity10420 and @entity4225 were 0.73, and 0.43, respectively, at both time points. CONCLUSION: @entity10420 and @entity4225 traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by @entity10420 and @entity4225 .

title: A longitudinal twin study of borderline and XXXX traits in early to middle adulthood.

entities_list: @entity4225 :: ('MESH:D001883', 'Disease') :: ['borderline personality disorder', 'BPD']

entities_list: @entity10420 :: ('MESH:D000987', 'Disease') :: ['ASPD', 'Antisocial personality disorder']

answer: @entity10420 :: (MESH:D000987,Disease) :: ['antisocial personality disorder']


abstract: INTRODUCTION: The objective of this study was to investigate the evidence for positive predictive value ( @entity2286 ) of alarm symptoms and combinations of symptoms for @entity14 , @entity0 and @entity2 in general practice. METHODS: This study is based on a literature search performed in PubMed, Embase, the Cochrane database and at ClinicalTrials.gov in accordance with the PRISMA guidelines. The main outcome measure used was @entity2286 . RESULTS: A total of 16 eligible studies were identified. The intervals in the brackets refer to the variation of the results in the studies. @entity14 : The @entity2286 of " @entity548 " was high for @entity1 > 60 years (6.6-21.2%), but much lower in younger age groups. For "change in bowel habits" and "significant general symptoms", the @entity2286 was 3.5-8.5%. @entity0 : "Palpable suspected @entity5 " was well supported (8.1-24%). No studies on the predictive value of "pitting of the skin", "papil-areola eczema/ulceration" and "suspect axillary lymph nodes" were found. @entity263 : One study showed a high @entity2286 for positive rectal examination (12%). The value for "lower urinary tract symptoms" was low (1.0-3.0%). @entity2286 for " @entity158 " and "haemospermia" were not found. @entity2 : For "haemoptysis" the @entity2286 increased from 8.4 in @entity1 aged 55 years to 20.4 at the age of > 85 years. @entity2286 for "cough", " @entity2531 " were low (0.4-1.1%). Using a new algorithm that estimates the @entity2286 of combinations of symptoms and risk factors, a higher @entity2286 may be achieved. CONCLUSION: A few of the alarm symptoms show a high @entity2286 , whereas the @entity2286 for some symptoms currently remains unknown. To improve the GPs' diagnostic judgment, a new algorithm for calculating the @entity2286 for combinations of symptoms and risk factors seems promising.

title: Predictive value of the official XXXX in general practice - a systematic review.

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

entities_list: @entity263 :: ('MESH:D011471', 'Disease') :: ['Prostate cancer']

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

entities_list: @entity548 :: ('MESH:D006470', 'Disease') :: ['rectal bleeding']

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

entities_list: @entity2 :: ('MESH:D008175', 'Disease') :: ['Lung cancer', 'lung cancer']

entities_list: @entity2531 :: ('MESH:D013001', 'Disease') :: ['pain in the thorax", "dyspnoea" and "general symptoms']

entities_list: @entity14 :: ('MESH:D015179', 'Disease') :: ['Colorectal cancer', 'colorectal cancer']

entities_list: @entity158 :: ('MESH:D010146', 'Disease') :: ['perianal pain']

answer: @entity5 :: (MESH:D009369,Disease) :: ['cancer alarm symptoms']


abstract: OBJECTIVES: To present our experience with four @entity808 treated by surgical excision and review the current literature. @entity808 are rare, benign @entity5 and infrequently present to the urologist. METHODS: From 1997 through 2002, the charts of 164 @entity1 with a diagnosis of benign retroperitoneal soft tissue mass were reviewed. Of those, four had a pathologic diagnosis of @entity808 . RESULTS: Three of the 4 @entity1 were @entity1 , with a median age of 54 years (range 46 to 80). The average @entity5 size was 13.7 cm (range 8.8 to 20). All @entity1 underwent magnetic resonance imaging, computed tomography, or ultrasonography, and 3 of the 4 @entity1 underwent a computed tomography-guided fine needle aspiration biopsy (all were either inaccurate or inconclusive). All @entity1 underwent complete @entity5 excision with free margins of resection and tolerated surgery without any complications. None of the @entity1 have had any evidence of recurrence at a mean follow-up of 26 months (range 10 to 48). CONCLUSIONS: @entity808 are difficult to diagnose preoperatively. Computed tomography-guided fine needle aspiration biopsy does not appear to provide an accurate preoperative diagnosis. The surgical approach should focus on complete excision of the mass. @entity1 undergoing complete surgical resection tend to do well without evidence of early recurrence.

title: XXXX : a case series and review of the literature.

entities_list: @entity808 :: ('MESH:D009442', 'Disease') :: ['retroperitoneal schwannoma', 'retroperitoneal schwannomas', 'Retroperitoneal schwannomas']

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

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

answer: @entity808 :: (MESH:D009442,Disease) :: ['Benign retroperitoneal schwannoma']


abstract: OBJECTIVES: To evaluate the oncologic adequacy of laparoscopic radical nephrectomy in @entity1 with pathologic Stage @entity1358 , we analyzed the long-term results in those treated with laparoscopy and those undergoing open surgery. METHODS: The @entity703 of 263 @entity1 was confirmed to be Stage T1 by pathologic examination of the radical nephrectomy specimen between January 1992 and June 2002. Of the 263 @entity1 , 195 were treated laparoscopically and the remaining 68 by open surgery. The @entity1 follow-up lasted until July 31, 2002. RESULTS: The follow-up period of the laparoscopy group was 2 to 121 months (median 40). A total of 183 @entity1 survived, 5 died of @entity703 , 7 died without any recurrent disease, and 7 were lost to follow-up. Seeding of the port sites did not develop in any of the @entity1 . Ten @entity1 had metastatic or recurrent disease within 3 to 110 months, and 5 of these @entity1 died of @entity5 within 12 to 86 months. The 5-year disease-free and @entity1 survival rate was 91%, and 94%, respectively. The 68 @entity1 who underwent open surgery were followed up for 11 to 126 months (median 65). Of the 68 @entity1 , 56 survived without any recurrent disease, 4 survived with metastasis, 6 died of metastatic disease within 8 to 49 months, and 6 were lost to follow-up. The 5-year disease-free and @entity1 survival rate was 87% and 94%, respectively. CONCLUSIONS: Laparoscopic radical nephrectomy is an alternative technique with comparable oncologic results to open nephrectomy in @entity1 with localized pathologic Stage @entity1358 .

title: Long-term outcome of laparoscopic radical nephrectomy for pathologic XXXX .

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

entities_list: @entity1358 :: ('MESH:D002292', 'Disease') :: ['T1 renal cell carcinoma']

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

entities_list: @entity703 :: ('MESH:D007680', 'Disease') :: ['renal tumor', 'renal cancer']

answer: @entity1358 :: (MESH:D002292,Disease) :: ['T1 renal cell carcinoma']


abstract: OBJECTIVES: A successful initial bladder closure is critical to the development of adequate bladder capacity and ultimate continence among @entity1 with @entity1494 . Although secure pelvic fixation is essential to success, the various methods of pelvic and extremity immobilization and their impact on surgical outcome have not previously been examined. METHODS: A review of the approved @entity1494 database at our institution identified 194 @entity1 for whom data were available regarding initial bladder closure and the method of pelvic immobilization. The records were reviewed with respect to age at bladder closure, use/type of osteotomy, method of pelvic immobilization, complications related to the immobilization technique, and surgical outcome. RESULTS: Of 194 @entity1 identified, initial exstrophy closure failed in 86. Of these 86 @entity1 , the initial closure failed in 80 at another hospital who were referred to our institution for additional treatment. Of the 114 initially closed at this institution, 6 failed. The success rates for initial and second closures were highest after osteotomy (75% versus 38% and 81.5% versus 27%, respectively), and when the @entity1 were immobilized with an external fixator and 6 to 8 weeks of modified Buck's traction with osteotomy (96%) or 4 to 6 weeks of modified Bryant's traction without osteotomy (61%). The spica cast and "mummy wrapping" immobilization techniques were less effective and were associated with significant complications. CONCLUSIONS: These results demonstrate that a successful exstrophy bladder closure depends on the proper use of the osteotomy and effective postoperative immobilization of the pelvis. Our best outcomes have been achieved using lower extremity traction (with or without external fixation of the pelvis).

title: Pelvic and extremity immobilization after XXXX closure: complications and impact on success.

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

answer: @entity1494 :: (MESH:D001745,Disease) :: ['bladder exstrophy']


abstract: OBJECTIVE: @entity120 in @entity1 after surgical intervention for @entity299 has been attributed to failure of the pulmonary endothelium to provide adequate vasodilation. Although we have shown that the impaired vasodilatory component attributable to the @entity534 - @entity842 pathway is almost completely reversible, a nonrestorable component persists, implying an additional vasoconstrictive mechanism in @entity358 . In this study of @entity1 after surgical intervention for @entity299 , we measured @entity2232 levels and used @entity11344 , a selective endothelin-A receptor antagonist, together with inhaled @entity842 to discriminate dysfunctional pulmonary endothelial vasodilation from endothelin-mediated pulmonary vasoconstriction. METHODS: All @entity1 were examined early after surgical intervention in the intensive care unit. Pulmonary vascular resistance (with respiratory mass spectrometry), as well as arterial and venous @entity2232 levels (measured by means of a quantitative enzyme-linked immunosorbent assay), were determined in 7 @entity1 (age range, 3.3-13.7 months; median age, 6.3 months) with intracardiac shunting defects at baseline and during ventilation with a fraction of inspired @entity26 of 0.65, with additional @entity11344 (0.1 mg/kg infused over 20 minutes), and with inhaled @entity842 (20 ppm). RESULTS: Pulmonary vascular resistance decreased from 7.7 +/- 3.4 at baseline to 6.1 +/- 2.8 Woods units. m(-2) (P =.022) at a fraction of inspired @entity26 of 0.65 and to 4.7 +/- 2.7 Woods units. m(-2) (P =.013) during @entity11344 infusion. Inhaled @entity842 had no further effect on pulmonary vascular resistance. Left atrial @entity2232 levels (1.35-5.12 pg/mL; mean, 2.4 pg/mL) correlated significantly with the decrease in pulmonary vascular resistance in response to @entity11344 infusion (r(2) = 0.89, P =.003). CONCLUSION: Postoperative elevation of pulmonary vascular resistance in @entity1 after surgical intervention for @entity299 is responsive to endothelin-A blockade with @entity11344 . Increased levels of @entity2232 predict the response to this therapy, which might become an important addition to the clinical armamentarium in @entity120 .

title: The endothelin antagonist @entity11344 reduces pulmonary vascular resistance after surgical intervention for XXXX .

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

entities_list: @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen']

entities_list: @entity120 :: ('MESH:D006976', 'Disease') :: ['Postoperative pulmonary hypertension', 'postoperative pulmonary hypertensive disease']

entities_list: @entity534 :: ('CHEBI:16467', 'Chemical') :: ['l-arginine']

entities_list: @entity358 :: ('MESH:D008171', 'Disease') :: ['postoperative pulmonary endothelial dysfunction']

entities_list: @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide']

entities_list: @entity299 :: ('MESH:D006331', 'Disease') :: ['congenital heart disease']

answer: @entity299 :: (MESH:D006331,Disease) :: ['congenital heart disease']


abstract: OBJECTIVE: @entity120 in @entity1 after surgical intervention for @entity299 has been attributed to failure of the pulmonary endothelium to provide adequate vasodilation. Although we have shown that the impaired vasodilatory component attributable to the @entity534 - @entity842 pathway is almost completely reversible, a nonrestorable component persists, implying an additional vasoconstrictive mechanism in @entity358 . In this study of @entity1 after surgical intervention for @entity299 , we measured @entity2232 levels and used @entity11344 , a selective endothelin-A receptor antagonist, together with inhaled @entity842 to discriminate dysfunctional pulmonary endothelial vasodilation from endothelin-mediated pulmonary vasoconstriction. METHODS: All @entity1 were examined early after surgical intervention in the intensive care unit. Pulmonary vascular resistance (with respiratory mass spectrometry), as well as arterial and venous @entity2232 levels (measured by means of a quantitative enzyme-linked immunosorbent assay), were determined in 7 @entity1 (age range, 3.3-13.7 months; median age, 6.3 months) with intracardiac shunting defects at baseline and during ventilation with a fraction of inspired @entity26 of 0.65, with additional @entity11344 (0.1 mg/kg infused over 20 minutes), and with inhaled @entity842 (20 ppm). RESULTS: Pulmonary vascular resistance decreased from 7.7 +/- 3.4 at baseline to 6.1 +/- 2.8 Woods units. m(-2) (P =.022) at a fraction of inspired @entity26 of 0.65 and to 4.7 +/- 2.7 Woods units. m(-2) (P =.013) during @entity11344 infusion. Inhaled @entity842 had no further effect on pulmonary vascular resistance. Left atrial @entity2232 levels (1.35-5.12 pg/mL; mean, 2.4 pg/mL) correlated significantly with the decrease in pulmonary vascular resistance in response to @entity11344 infusion (r(2) = 0.89, P =.003). CONCLUSION: Postoperative elevation of pulmonary vascular resistance in @entity1 after surgical intervention for @entity299 is responsive to endothelin-A blockade with @entity11344 . Increased levels of @entity2232 predict the response to this therapy, which might become an important addition to the clinical armamentarium in @entity120 .

title: The endothelin antagonist XXXX reduces pulmonary vascular resistance after surgical intervention for @entity299 .

answer: @entity11344 :: (MESH:C072247,Chemical) :: ['BQ123']


abstract: In this paper, we briefly review the relation between @entity5 and @entity1211 ( @entity1211 ), an association that has been recognized for more than a century. In particular we focus on @entity1211 as predictor and prognostic factor for @entity5 and the antineoplastic potential of antithrombotic treatment. @entity5 may cause disturbances in the haemostatic system by numerous mechanisms that can lead to an increased risk of @entity1211 . @entity1 with known @entity5 are at increased risk of @entity1211 ; however, @entity1211 may also be a predictor of subsequent @entity5 in the years afterwards. Furthermore, @entity5 @entity1 with @entity1211 are more likely to have @entity1442 and a worse prognosis than @entity5 @entity1 without a @entity1211 episode. These findings may have implications for the clinical care of @entity1 with @entity1211 in terms of screening for @entity5 . However, extensive @entity5 screening programs are not recommended in general for @entity1 with @entity1211 . A wide range of antithrombotic drugs including heparin, oral anticoagulants, and platelet inhibitors have been examined in order to study the effect on the prevention and treatment of various @entity5 . These efforts have resulted in a considerable amount of useful data from animal models and a number of promising reports from retrospective analyses and small-scale trials linking antithrombotic treatment with an increased survival in @entity5 @entity1 and even a lower risk of primary @entity5 . However, the clinical implications of these findings must await properly designed and conducted randomized clinical trials.

title: XXXX : a multidisciplinary approach.

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'cancer', 'Cancer']

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

entities_list: @entity1442 :: ('MESH:D020178', 'Disease') :: ['advanced disease']

entities_list: @entity1211 :: ('MESH:D054556', 'Disease') :: ['VTE', 'venous thromboembolism']

answer: @entity1211 :: (MESH:D054556,Disease) :: ['Cancer and venous thromboembolism']


abstract: PURPOSE: We examined the feasibility and effectiveness of bronchial arterial infusion (BAI) as induction chemotherapy before surgery for locally advanced @entity1149 ( @entity1149 ). METHODS: Eighteen @entity1 with locally advanced @entity1149 were given BAI consisting of @entity900 (CDDP) (50-100 mg/m(2)) as induction chemotherapy before surgery (induction BAI). Six @entity1 with clinical stage IIIA @entity5 had bulky N2 metastatic lymph nodes, and 12 @entity1 with clinical stage IIIB @entity5 had @entity66 . RESULTS: Of the 18 @entity1 , 12 (67%) showed a partial response to the BAI therapy. Standard pulmonary resection was performed in 5 @entity1 , pulmonary resection with the combined resection of adjacent organs was performed in 10 @entity1 , and pulmonary resection with carinal resection and reconstruction was performed in 3 @entity1 . Complete resection was possible in 14 @entity1 (78%). There were no serious BAI therapy-related complications or @entity204 . The 5-year survival rate of the 18 @entity1 was 35.7% and the @entity1349 ( @entity1349 ) was 19.4 months. Survival was better when complete resection was achieved after the induction BAI, especially in @entity1 with stage IIIB (T4) disease. CONCLUSION: Based on our preliminary findings, BAI with CDDP as induction chemotherapy is feasible and may be an effective therapeutic modality for locally advanced @entity1149 .

title: Feasibility of induction chemotherapy using bronchial arterial infusion for locally advanced XXXX : a pilot study.

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

entities_list: @entity66 :: ('MESH:D004194', 'Disease') :: ['T4 disease']

entities_list: @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small cell lung cancer']

entities_list: @entity900 :: ('MESH:D002945', 'Chemical') :: ['cis-diamminedichloroplatinum']

entities_list: @entity204 :: ('MESH:D003643', 'Disease') :: ['postoperative deaths']

entities_list: @entity1349 :: ('MESH:D011475', 'Disease') :: ['median survival time', 'MST']

answer: @entity1149 :: (MESH:D002289,Disease) :: ['non-small cell lung cancer']


abstract: It is assumed that @entity172 influences bone strength and risk of @entity174 by affecting @entity79 ( @entity79 ). However, @entity172 may influence the mechanical strength of bones by altering the structural geometry in ways that may not be apparent in the density. Repeated dual energy X-ray absorptiometry (DXA) hip scan data were analyzed for bone density and structural geometry in elderly @entity1 participating in the @entity3604 ( @entity3604 ). Scans were studied with a hip structural analysis program for the effects of @entity172 replacement therapy (ERT) on @entity79 and structural geometry. Of the 3,964 @entity1 with ERT-use data, 588 used ERT at both the start and end of the approximately 3.5-year study, 1,203 had past use which was discontinued by clinic visit 4, and 2,163 @entity1 had never used ERT. All groups lost @entity79 at the femoral neck, but the reduced @entity79 among users of ERT was entirely due to subperiosteal expansion and not @entity604 , whereas both @entity604 and expansion occurred in past or nonusers. @entity79 increased 0.8%/year at the femoral shaft among ERT users but decreased 0.8%/year among nonusers. Section moduli increased at both the neck and shaft among ERT users but remained unchanged in past and nonusers. Current, but not past, use of @entity172 therapy in elderly @entity1 seems to increase mechanical strength of the proximal femur by improving its geometric properties. These effects are not evident from changes in femoral neck @entity79 .

title: Effects of current and discontinued XXXX replacement therapy on hip structural geometry: the study of @entity3604 .

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

entities_list: @entity3604 :: ('MESH:D058866', 'Disease') :: ['SOF', 'Study of Osteoporotic Fractures']

entities_list: @entity174 :: ('MESH:D050723', 'Disease') :: ['fractures']

entities_list: @entity604 :: ('MESH:D016301', 'Disease') :: ['bone loss']

entities_list: @entity79 :: ('MESH:D001847', 'Disease') :: ['bone mineral density', 'BMD']

answer: @entity172 :: (MESH:D004967,Chemical) :: ['estrogen']


abstract: It is assumed that @entity172 influences bone strength and risk of @entity174 by affecting @entity79 ( @entity79 ). However, @entity172 may influence the mechanical strength of bones by altering the structural geometry in ways that may not be apparent in the density. Repeated dual energy X-ray absorptiometry (DXA) hip scan data were analyzed for bone density and structural geometry in elderly @entity1 participating in the @entity3604 ( @entity3604 ). Scans were studied with a hip structural analysis program for the effects of @entity172 replacement therapy (ERT) on @entity79 and structural geometry. Of the 3,964 @entity1 with ERT-use data, 588 used ERT at both the start and end of the approximately 3.5-year study, 1,203 had past use which was discontinued by clinic visit 4, and 2,163 @entity1 had never used ERT. All groups lost @entity79 at the femoral neck, but the reduced @entity79 among users of ERT was entirely due to subperiosteal expansion and not @entity604 , whereas both @entity604 and expansion occurred in past or nonusers. @entity79 increased 0.8%/year at the femoral shaft among ERT users but decreased 0.8%/year among nonusers. Section moduli increased at both the neck and shaft among ERT users but remained unchanged in past and nonusers. Current, but not past, use of @entity172 therapy in elderly @entity1 seems to increase mechanical strength of the proximal femur by improving its geometric properties. These effects are not evident from changes in femoral neck @entity79 .

title: Effects of current and discontinued @entity172 replacement therapy on hip structural geometry: the study of XXXX .

answer: @entity3604 :: (MESH:D058866,Disease) :: ['osteoporotic fractures']


abstract: An UV absorption and CD study of intestinal @entity844 -binding protein is presented. Since there are only two Trp residues in the molecule, two single-Trp mutants were prepared to deconvolute their signals. The individual contribution of the eight @entity815 and four Tyr residues was not established; however, @entity815 global contribution is relatively free of interferences from the other chromophores and was observed directly. CD spectra showed that @entity815 vibronic structure was unusually sharp and seems to monitor very specific details in the three-dimensional structure. The global signal from Tyr was assigned only approximately due to band broadening and overlapping. At the upper end of the CD spectrum, strong positive (1)L(b) Trp transitions from Trp 82 and strong negative (1)L(b) Trp transitions from @entity18811 were observed. (1)L(a) transitions were overall weak, positive for Trp 82 and negative for @entity18811 , nearly cancelling each other out in the final spectrum. The above assignment is of practical and fundamental interest to monitor folding, binding, and molecular dynamics down to microdomain resolution. The assignment of Trp bands allowed comparison with previous data from @entity54044 , another member of the IFABP family with 28% identical residues. It was found that structural homology extends beyond sequence and tertiary fold to include optical properties of equivalent Trp residues in the structure.

title: Tryptophan mutants of intestinal XXXX -binding protein: ultraviolet absorption and circular dichroism studies.

entities_list: @entity844 :: ('CHEBI:35366', 'Chemical') :: ['fatty acid']

answer: @entity844 :: (CHEBI:35366,Chemical) :: ['fatty acid']


abstract: UNASSIGNED: Septins are a conserved family of GTPases that regulate important cellular processes such as cell wall integrity, and septation in fungi. The requirement of septins for virulence has been demonstrated in the @entity1 pathogenic @entity375 @entity5132 and @entity1327 , as well as the plant pathogen @entity8812 . @entity54 spp. contains five genes encoding for septins (aspA-E). While the importance of septins AspA, AspB, AspC, and AspE for growth and conidiation has been elucidated in the filamentous fungal model @entity14940 , nothing is known on the role of septins in growth and virulence in the @entity1 pathogen @entity54 . Here we deleted all five A. fumigatus septins, and generated certain double and triple septin deletion strains. Phenotypic analyses revealed that while all the septins are dispensable in normal growth conditions, AspA, AspB, AspC and AspE are required for regular septation. Furthermore, deletion of only the core septin genes significantly reduced conidiation. Concomitant with the absence of an electron-dense outer conidial wall, the   aspB strain was also sensitive to anti-cell wall agents. Infection with the   aspB strain in a Galleria mellonella model of @entity3 showed hypervirulence, but no virulence difference was noted when compared to the wild-type strain in a @entity19 model of @entity3 . Although the deletion of aspB resulted in increased release of TNF-a from the macrophages, no significant @entity32 differences in lung histology was noted between the   aspB strain and the wild-type strain. Taken together, these results point to the importance of septins in A. fumigatus growth, but not virulence in a @entity19 model.

title: The XXXX septins play pleiotropic roles in septation, conidiation, and cell wall stress, but are dispensable for virulence.

entities_list: @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation']

entities_list: @entity1327 :: ('5207', 'Species') :: ['Cryptococcus neoformans']

entities_list: @entity14940 :: ('162425', 'Species') :: ['Aspergillus nidulans']

entities_list: @entity5132 :: ('5476', 'Species') :: ['Candida albicans']

entities_list: @entity54 :: ('746128', 'Species') :: ['Aspergillus fumigatus', 'Aspergillus']

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

entities_list: @entity8812 :: ('318829', 'Species') :: ['Magnaporthe oryzae']

answer: @entity54 :: (746128,Species) :: ['Aspergillus fumigatus']


abstract: The side chain of @entity492 95 in flavodoxin from @entity31539 provides the closest negative charge to N(1) of the bound FMN in the protein. Site-directed mutagenesis was used to substitute @entity493 , @entity2734 , or @entity2227 for this @entity535 to assess the effect of this charge on the @entity13478 / @entity8156 redox potential (E(1)) of the FMN cofactor. The @entity70583 mutation shifts the E(1) redox potential positively by 16 mV, while a negative shift of 23 mV occurs in the oxidized/ @entity13478 midpoint redox potential (E(2)). The crystal structures of the oxidized and @entity13478 forms of this mutant are similar to the corresponding states of the wild-type protein. In contrast to the wild-type protein, a further change in structure occurs in the @entity70583 mutant in the @entity8156 form. The side chain of Y98 flips into an energetically more favorable edge-to-face interaction with the bound FMN. Analysis of the structural changes in the @entity70583 mutant, taking into account electrostatic interactions at the FMN binding site, suggests that the pi-pi electrostatic repulsions have only a minor contribution to the very low E(1) redox potential of the FMN cofactor when bound to apoflavodoxin. Substitution of D95 with @entity2227 causes only a slight perturbation of the two one-electron redox potentials of the FMN cofactor. The structure of the @entity70584 mutant reveals a large movement of the 60-loop (residues 60-64) away from the @entity1785 in the oxidized structure. Reduction of this mutant to the @entity8156 causes the conformation of the 60-loop to revert back to that occurring in the structures of the wild-type protein. The crystal structures of the @entity70584 mutant imply that electrostatic repulsion between a @entity3338 on the side chain at position 95 and the @entity3971 ring of Y98 prevents rotation of the Y98 side chain to a more energetically favorable conformation as occurs in the @entity70583 mutant. Replacement of D95 with @entity2734 has no effect on E(2) but causes E(1) to change by 45 mV. The @entity70585 mutant failed to crystallize. The K(d) values of the protein FMN complex in all three oxidation-reduction states differ from those of the wild-type complexes. Molecular modeling showed that the conformational energy of the protein changes with the redox state, in qualitative agreement with the observed changes in K(d), and allowed the electrostatic interactions between the FMN and the surrounding groups on the protein to be quantified.

title: Crystallographic investigation of the role of XXXX 95 in the modulation of the redox potentials of @entity31539 flavodoxin.

entities_list: @entity31539 :: ('881', 'Species') :: ['Desulfovibrio vulgaris']

entities_list: @entity70585 :: ('p|SUB|D|95|N', 'ProteinMutation') :: ['D95N']

entities_list: @entity2227 :: ('CHEBI:29987', 'Chemical') :: ['glutamate']

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

entities_list: @entity8156 :: ('MESH:C031927', 'Chemical') :: ['hydroquinone']

entities_list: @entity70584 :: ('p|SUB|D|95|E', 'ProteinMutation') :: ['D95E']

entities_list: @entity2734 :: ('CHEBI:17196', 'Chemical') :: ['asparagine']

entities_list: @entity13478 :: ('CHEBI:15817', 'Chemical') :: ['semiquinone']

entities_list: @entity70583 :: ('p|SUB|D|95|A', 'ProteinMutation') :: ['D95A']

entities_list: @entity492 :: ('CHEBI:29995', 'Chemical') :: ['aspartate']

entities_list: @entity3338 :: ('CHEBI:35757', 'Chemical') :: ['carboxylate']

entities_list: @entity493 :: ('CHEBI:16449', 'Chemical') :: ['alanine']

answer: @entity492 :: (CHEBI:29995,Chemical) :: ['aspartate']


abstract: The side chain of @entity492 95 in flavodoxin from @entity31539 provides the closest negative charge to N(1) of the bound FMN in the protein. Site-directed mutagenesis was used to substitute @entity493 , @entity2734 , or @entity2227 for this @entity535 to assess the effect of this charge on the @entity13478 / @entity8156 redox potential (E(1)) of the FMN cofactor. The @entity70583 mutation shifts the E(1) redox potential positively by 16 mV, while a negative shift of 23 mV occurs in the oxidized/ @entity13478 midpoint redox potential (E(2)). The crystal structures of the oxidized and @entity13478 forms of this mutant are similar to the corresponding states of the wild-type protein. In contrast to the wild-type protein, a further change in structure occurs in the @entity70583 mutant in the @entity8156 form. The side chain of Y98 flips into an energetically more favorable edge-to-face interaction with the bound FMN. Analysis of the structural changes in the @entity70583 mutant, taking into account electrostatic interactions at the FMN binding site, suggests that the pi-pi electrostatic repulsions have only a minor contribution to the very low E(1) redox potential of the FMN cofactor when bound to apoflavodoxin. Substitution of D95 with @entity2227 causes only a slight perturbation of the two one-electron redox potentials of the FMN cofactor. The structure of the @entity70584 mutant reveals a large movement of the 60-loop (residues 60-64) away from the @entity1785 in the oxidized structure. Reduction of this mutant to the @entity8156 causes the conformation of the 60-loop to revert back to that occurring in the structures of the wild-type protein. The crystal structures of the @entity70584 mutant imply that electrostatic repulsion between a @entity3338 on the side chain at position 95 and the @entity3971 ring of Y98 prevents rotation of the Y98 side chain to a more energetically favorable conformation as occurs in the @entity70583 mutant. Replacement of D95 with @entity2734 has no effect on E(2) but causes E(1) to change by 45 mV. The @entity70585 mutant failed to crystallize. The K(d) values of the protein FMN complex in all three oxidation-reduction states differ from those of the wild-type complexes. Molecular modeling showed that the conformational energy of the protein changes with the redox state, in qualitative agreement with the observed changes in K(d), and allowed the electrostatic interactions between the FMN and the surrounding groups on the protein to be quantified.

title: Crystallographic investigation of the role of @entity492 95 in the modulation of the redox potentials of XXXX flavodoxin.

answer: @entity31539 :: (881,Species) :: ['Desulfovibrio vulgaris']


abstract: OBJECTIVE: We reviewed our experience with iatrogenic chylothorax after pulmonary resections for @entity2 to evaluate our treatment strategy and to identify factors that predict the need for reoperation. METHODS: From July 1992 through February 2000, a total of 1110 @entity1 underwent pulmonary resection (at least lobectomy) and systematic mediastinal lymph node dissection for @entity2 at our division. Twenty-seven @entity1 (2.4%) had postoperative chylothorax develop. We initially treated 26 of these @entity1 conservatively with complete oral intake cessation and total parenteral nutrition, and these @entity1 constituted the subjects in this study. RESULTS: There were 21 @entity1 and 5 @entity1 with a median age of 62 years (range 44 to 80 years). The initial procedures were pneumonectomy in 2 cases, bilobectomy in 1 case, and lobectomy in 23 cases. Twenty-one @entity1 (81%) had the condition cured with conservative treatment. These @entity1 resumed a normal diet at a median of 8 days after chylothorax diagnosis (range 4-35 days). The remaining 5 @entity1 (19%) underwent reoperation at a median of 14 days after diagnosis (range 5-35 days). Chest tube drainage of less than 500 mL during the first 24 hours after complete oral intake cessation and total parenteral nutrition predicted a cure with conservative treatment. CONCLUSION: Although most cases of chylothorax after pulmonary resection with systematic mediastinal lymph node dissection can be cured with a conservative strategy, early surgical intervention may be indicated if chest tube drainage is more than 500 mL during the first 24 hours after complete oral intake cessation and total parenteral nutrition.

title: Treatment strategy for chylothorax after pulmonary resection and lymph node dissection for XXXX .

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

entities_list: @entity2 :: ('MESH:D008175', 'Disease') :: ['lung cancer']

answer: @entity2 :: (MESH:D008175,Disease) :: ['lung cancer']


abstract: The aim of this study was to clarify the relationship between endogenous @entity172 , @entity443 ( @entity443 ), and @entity604 in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 @entity1 -50 @entity1 in each of four age decades-were randomly selected, and baseline @entity79 ( @entity79 ) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total @entity53 (total E2) and @entity443 were measured, and @entity10684 ( @entity10684 ) was calculated using @entity443 and the percent @entity443 -unbound fraction ratio. @entity79 was measured again 3 years later, in 1996. @entity1 with ovariectomy or hysterectomy were excluded, and the remaining @entity1 were categorized into four groups: premenopausal ( n = 38), perimenopausal ( n = 14), postmenopausal group 1 (5 years or less since menopause; n = 18), and postmenopausal group 2 (6 years or more since menopause; n = 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for @entity10684 showed the same pattern across the groups. After the multiple regression analysis of @entity79 at follow-up and endogenous @entity172 , in premenopausal @entity1 , there were no significant associations between @entity79 at follow-up and serum total E2 and @entity10684 . In perimenopausal women, however, serum total E2 and @entity10684 were significantly correlated with trochanteric @entity79 at follow-up ( P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle @entity79 at follow-up ( P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between @entity79 at follow-up and @entity443 , in the premenopausal group, serum levels of @entity443 were negatively correlated with @entity79 at the femoral neck ( P < 0.05). In regard to partial regression coefficients for the change rates of @entity79 over 3 years and serum @entity172 and @entity443 concentrations, in perimenopausal @entity1 , @entity10684 was correlated with the change rate of @entity79 at Ward's triangle ( P < 0.05), and in postmenopausal group 1, serum levels of @entity443 were significantly negatively related to change in @entity79 at the trochanter ( P < 0.01). No other relationships with change in @entity79 were observed at any sites. These findings suggest that serum E2, @entity10684 , and @entity443 levels differentially predict @entity79 levels in groups of differing menstrual status. It would, however, be difficult to predict @entity604 in middle-aged and elderly Japanese @entity1 over a 3-year period using these indices alone.

title: The relationship between endogenous @entity172 , @entity443 , and XXXX in female residents of a rural Japanese community: the Taiji Study.

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

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

entities_list: @entity604 :: ('MESH:D016301', 'Disease') :: ['bone loss']

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

entities_list: @entity79 :: ('MESH:D001847', 'Disease') :: ['bone mineral density', 'BMD']

entities_list: @entity443 :: ('6462', 'Gene') :: ['sex hormone-binding globulin', 'SHBG']

answer: @entity604 :: (MESH:D016301,Disease) :: ['bone loss']


abstract: The aim of this study was to clarify the relationship between endogenous @entity172 , @entity443 ( @entity443 ), and @entity604 in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 @entity1 -50 @entity1 in each of four age decades-were randomly selected, and baseline @entity79 ( @entity79 ) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total @entity53 (total E2) and @entity443 were measured, and @entity10684 ( @entity10684 ) was calculated using @entity443 and the percent @entity443 -unbound fraction ratio. @entity79 was measured again 3 years later, in 1996. @entity1 with ovariectomy or hysterectomy were excluded, and the remaining @entity1 were categorized into four groups: premenopausal ( n = 38), perimenopausal ( n = 14), postmenopausal group 1 (5 years or less since menopause; n = 18), and postmenopausal group 2 (6 years or more since menopause; n = 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for @entity10684 showed the same pattern across the groups. After the multiple regression analysis of @entity79 at follow-up and endogenous @entity172 , in premenopausal @entity1 , there were no significant associations between @entity79 at follow-up and serum total E2 and @entity10684 . In perimenopausal women, however, serum total E2 and @entity10684 were significantly correlated with trochanteric @entity79 at follow-up ( P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle @entity79 at follow-up ( P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between @entity79 at follow-up and @entity443 , in the premenopausal group, serum levels of @entity443 were negatively correlated with @entity79 at the femoral neck ( P < 0.05). In regard to partial regression coefficients for the change rates of @entity79 over 3 years and serum @entity172 and @entity443 concentrations, in perimenopausal @entity1 , @entity10684 was correlated with the change rate of @entity79 at Ward's triangle ( P < 0.05), and in postmenopausal group 1, serum levels of @entity443 were significantly negatively related to change in @entity79 at the trochanter ( P < 0.01). No other relationships with change in @entity79 were observed at any sites. These findings suggest that serum E2, @entity10684 , and @entity443 levels differentially predict @entity79 levels in groups of differing menstrual status. It would, however, be difficult to predict @entity604 in middle-aged and elderly Japanese @entity1 over a 3-year period using these indices alone.

title: The relationship between endogenous @entity172 , XXXX , and @entity604 in female residents of a rural Japanese community: the Taiji Study.

answer: @entity443 :: (6462,Gene) :: ['sex hormone-binding globulin']


abstract: The aim of this study was to clarify the relationship between endogenous @entity172 , @entity443 ( @entity443 ), and @entity604 in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 @entity1 -50 @entity1 in each of four age decades-were randomly selected, and baseline @entity79 ( @entity79 ) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total @entity53 (total E2) and @entity443 were measured, and @entity10684 ( @entity10684 ) was calculated using @entity443 and the percent @entity443 -unbound fraction ratio. @entity79 was measured again 3 years later, in 1996. @entity1 with ovariectomy or hysterectomy were excluded, and the remaining @entity1 were categorized into four groups: premenopausal ( n = 38), perimenopausal ( n = 14), postmenopausal group 1 (5 years or less since menopause; n = 18), and postmenopausal group 2 (6 years or more since menopause; n = 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for @entity10684 showed the same pattern across the groups. After the multiple regression analysis of @entity79 at follow-up and endogenous @entity172 , in premenopausal @entity1 , there were no significant associations between @entity79 at follow-up and serum total E2 and @entity10684 . In perimenopausal women, however, serum total E2 and @entity10684 were significantly correlated with trochanteric @entity79 at follow-up ( P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle @entity79 at follow-up ( P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between @entity79 at follow-up and @entity443 , in the premenopausal group, serum levels of @entity443 were negatively correlated with @entity79 at the femoral neck ( P < 0.05). In regard to partial regression coefficients for the change rates of @entity79 over 3 years and serum @entity172 and @entity443 concentrations, in perimenopausal @entity1 , @entity10684 was correlated with the change rate of @entity79 at Ward's triangle ( P < 0.05), and in postmenopausal group 1, serum levels of @entity443 were significantly negatively related to change in @entity79 at the trochanter ( P < 0.01). No other relationships with change in @entity79 were observed at any sites. These findings suggest that serum E2, @entity10684 , and @entity443 levels differentially predict @entity79 levels in groups of differing menstrual status. It would, however, be difficult to predict @entity604 in middle-aged and elderly Japanese @entity1 over a 3-year period using these indices alone.

title: The relationship between endogenous XXXX , @entity443 , and @entity604 in female residents of a rural Japanese community: the Taiji Study.

answer: @entity172 :: (MESH:D004967,Chemical) :: ['estrogen']


abstract: INTRODUCTION: The i.v. administration of the cytoprotective agent @entity8503 is associated with reversible clinical @entity551 , protracted emesis, and malaise in a various percentage of @entity1 . We evaluated, prospectively, whether the s.c. route is a better tolerated alternative to the i.v. route in @entity1 receiving chemotherapy. @entity1 AND METHODS: Fifty-nine @entity1 treated with "once every 2 weeks" regimens received 1000 mg of @entity8503 i.v. before chemotherapy. @entity1 who developed protracted @entity391 and malaise and/or clinical @entity551 for two consecutive i.v. administrations received the same dose of @entity8503 s.c. for the subsequent cycles (i.v./s.c. study). In an additional cohort of 12 @entity1 (s.c. study), 1000 mg of @entity8503 were given s.c. since the first chemotherapy cycle. RESULTS: In the i.v./s.c. study, 8 (13.5%) @entity1 showed protracted emesis/malaise and/or clinical @entity551 during the first two cycles. An additional 4 (6.6%) @entity1 developed similar side effects during the subsequent cycles. Switching to the s.c. route, an improved tolerance was noted. In the s.c. study, a total of 76 injections was administered. Protracted @entity391 or clinical @entity551 was absent, and this tolerance profile was significantly better than the i.v. one (P = 0.001). There were no other systemic side effects related to the s.c. administration. CONCLUSIONS: @entity8503 , at a dose of 1000 mg, is better tolerated when administered s.c. Switching to the s.c. route in @entity1 with poor tolerance using the i.v. administration allows the continuation of cytoprotection with minor side effects. Although preliminary, 1000 mg of @entity8503 effectively protected against the lower, still more frequently administered doses of chemotherapy given once every 2 weeks.

title: XXXX before chemotherapy: improved tolerance profile of the subcutaneous over the intravenous route.

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

entities_list: @entity8503 :: ('MESH:D004999', 'Chemical') :: ['Amifostine', 'amifostine']

entities_list: @entity551 :: ('MESH:D007022', 'Disease') :: ['hypotension']

entities_list: @entity391 :: ('MESH:D014839', 'Disease') :: ['vomiting']

answer: @entity8503 :: (MESH:D004999,Chemical) :: ['Amifostine']


abstract: PURPOSE: Green tea and green tea @entity6398 have been shown to possess @entity5 preventive activities in preclinical model systems. In preparation for future green tea intervention trials, we have conducted a clinical study to determine the safety and pharmacokinetics of green tea @entity6398 after 4 weeks of daily p.o. administration of @entity3089 ( @entity3090 ) or Polyphenon E (a defined, decaffeinated green tea @entity3978 mixture). In an exploratory fashion, we have also determined the effect of chronic green tea @entity3978 administration on UV-induced @entity5105 response. EXPERIMENTAL DESIGN: Healthy @entity1 with @entity272 or III underwent a 2-week run-in period and were randomly assigned to receive one of the five treatments for 4 weeks: 800 mg @entity3090 once/day, 400 mg @entity3090 twice/day, 800 mg @entity3090 as Polyphenon E once/day, 400 mg @entity3090 as Polyphenon E twice/day, or a placebo once/day (8 subjects/group). Samples were collected and measurements performed before and after the 4-week treatment period for determination of safety, pharmacokinetics, and biological activity of green tea @entity3978 treatment. RESULTS: Adverse events reported during the 4-week treatment period include excess gas, upset stomach, @entity390 , heartburn, @entity158 , @entity490 , @entity1296 , @entity10 , and @entity925 . All of the reported events were rated as mild events. For most events, the incidence reported in the @entity3978 -treated groups was not more than that reported in the placebo group. No significant changes were observed in blood counts and blood chemistry profiles after repeated administration of green tea @entity3978 products. There was a >60% increase in the area under the plasma @entity3090 concentration-time curve after 4 weeks of green tea @entity3978 treatment at a dosing schedule of 800 mg once daily. No significant changes were observed in the pharmacokinetics of @entity3090 after repeated green tea @entity3978 treatment at a regimen of 400 mg twice daily. The pharmacokinetics of the conjugated metabolites of @entity15359 and @entity12919 were not affected by repeated green tea @entity3978 treatment. Four weeks of green tea @entity3978 treatment at the selected dose and dosing schedule did not provide protection against UV-induced @entity5105 . CONCLUSIONS: We conclude that it is safe for healthy individuals to take green tea @entity3978 products in amounts equivalent to the @entity3090 content in 8-16 cups of green tea once a day or in divided doses twice a day for 4 weeks. There is a >60% increase in the systemic availability of free @entity3090 after chronic green tea @entity3978 administration at a high daily bolus dose (800 mg @entity3090 or Polyphenon E once daily).

title: Pharmacokinetics and safety of green tea XXXX after multiple-dose administration of @entity3089 and polyphenon E in healthy individuals.

entities_list: @entity3978 :: ('CHEBI:26195', 'Chemical') :: ['polyphenol']

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

entities_list: @entity1296 :: ('MESH:D004244', 'Disease') :: ['dizziness']

entities_list: @entity15359 :: ('MESH:C057580', 'Chemical') :: ['epigallocatechin']

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

entities_list: @entity12919 :: ('MESH:D002392', 'Chemical') :: ['epicatechin']

entities_list: @entity3089 :: ('MESH:C045651', 'Chemical') :: ['epigallocatechin gallate']

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

entities_list: @entity158 :: ('MESH:D010146', 'Disease') :: ['stomach ache']

entities_list: @entity272 :: ('MESH:D012871', 'Disease') :: ['Fitzpatric skin type II']

entities_list: @entity490 :: ('MESH:D015746', 'Disease') :: ['abdominal pain']

entities_list: @entity6398 :: ('MESH:D059808', 'Chemical') :: ['polyphenols']

entities_list: @entity925 :: ('MESH:D063806', 'Disease') :: ['muscle pain']

answer: @entity6398 :: (MESH:D059808,Chemical) :: ['polyphenols']