abstract: @entity54 is an important opportunistic fungal pathogen that causes lethal systemic invasive @entity2381 . It must be able to adapt to stress in the microenvironment during host invasion and systemic spread. The high-osmolarity @entity653 (HOG) mitogen-activated protein kinase (MAPK) signaling pathway is a key element that controls adaptation to environmental stress. It plays a critical role in the virulence of several fungal pathogens. In this review, we summarize the current knowledge about the functions of different components of the HOG-MAPK pathway in A. fumigatus through mutant analysis or inferences from the genome annotation, focusing on their roles in adaptation to stress, regulation of infection-related morphogenesis, and effect on virulence. We also briefly compare the functions of the HOG pathway in A. fumigatus with those in the model fungi @entity375 and @entity14940 as well as several other @entity1 and plant pathogens including @entity5132 , @entity1327 , and @entity8812 . The genes described in this review mainly include tcsB, fos1, skn7, sho1, pbs2, and sakA whose deletion mutants have already been established in A. fumigatus. Among them, fos1 has been considered a virulence factor in A. fumigatus, indicating that components of the HOG pathway may be suitable as targets for developing new fungicides. However, quite a few of the genes of this pathway, such as sskA (ssk1), sskB, steC, and downstream regulator genes, are not well characterized. System biology approaches may contribute to a more comprehensive understanding of HOG pathway functions with dynamic details.

title: Current understanding of HOG-MAPK pathway in XXXX .

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

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

entities_list: @entity653 :: ('MESH:D005990', 'Chemical') :: ['glycerol']

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

entities_list: @entity2381 :: ('MESH:D001228', 'Disease') :: ['aspergillosis']

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

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

entities_list: @entity375 :: ('4932', 'Species') :: ['Saccharomyces cerevisiae']

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


abstract: At the 11th annual meeting of the Society of Urologic Oncology, an expert panel was convened to discuss the practical use of perioperative chemotherapy for @entity150 . The discussion was structured as a case-based debate among the panelists. The topics included: neoadjuvant chemotherapy with a focus on T2 disease, pros and cons, survival data, tolerability of @entity900 -based therapy, can we avoid radical cystectomy in complete responders, limitations and alternatives to @entity900 -based therapy, management of 'suboptimal' chemotherapy, @entity66 after neoadjuvant chemotherapy, adjuvant chemotherapy, and key aspects of radical cystectomy and lymph-node dissection in multimodal therapy. The presentations were derived from published literature. The panelists agreed that @entity1 with @entity150 should be managed with a multidisciplinary team, including urologist and medical oncologist. @entity900 -based neoadjuvant chemotherapy has demonstrated improved survival and should be incorporated into the management of all eligible @entity1 with @entity150 . However, in some centers, neoadjuvant chemotherapy is reserved for @entity1 with >T2 disease or high-risk features. There are no data for the administration of non- @entity900 -based neoadjuvant chemotherapy, such as @entity3003 -combinations. @entity900 -ineligible @entity1 should proceed directly to surgical extirpation with adjuvant @entity900 -based chemotherapy considered based on pathologic findings. However, the data for adjuvant chemotherapy is less compelling. As our refinement of the selection process continues, we may be able to better identify subsets of @entity1 who may be spared chemotherapy, but much work remains to be done in this arena. The current standard for @entity150 @entity1 is @entity900 -based neoadjuvant chemotherapy followed by radical cystectomy and pelvic lymph-node dissection.

title: Practical use of perioperative chemotherapy for XXXX : summary of session at the Society of Urologic Oncology annual meeting.

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

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

entities_list: @entity3003 :: ('MESH:D016190', 'Chemical') :: ['carboplatin']

entities_list: @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin', 'Cisplatin']

entities_list: @entity150 :: ('MESH:D001749', 'Disease') :: ['muscle-invasive bladder cancer']

answer: @entity150 :: (MESH:D001749,Disease) :: ['muscle-invasive bladder cancer']


abstract: AIMS AND BACKGROUND: The optimal salvage therapy for recurrent @entity43 has not been clearly established. Response to second-line chemotherapy is low, with a short median survival (8.8-15 months). We investigated the effect of an @entity146 approach consisting of surgery followed by intraperitoneal drug delivery and local @entity221 . @entity1 AND METHODS: In a phase II clinical study, 27 @entity1 with advanced/recurrent @entity43 were treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Median @entity1 age was 53 years (range, 30-67) and mean follow-up was 17.4 months (range, 0.3-36.0). @entity1 had been surgically staged and heavily pretreated with @entity900 -based, @entity1311 -based or @entity1311 / @entity902 -containing regimens. Nineteen (70%) @entity1 were cytoreduced to minimal @entity66 <2.5 mm. The intraperitoneal hyperthermic perfusion was performed with the closed abdomen technique, using a preheated polysaline perfusate containing @entity900 (25 mg/m2/L) + @entity1138 (3.3 mg/m2/L) through a heart-lung pump (mean flow of 700 mL/min) for 60 min in the hyperthermic phase (42.5 degrees C). RESULTS: Two-year overall survival was 55%. Median times to overall progression and local progression were 16 months and 21.8 months, respectively. Variables that affected the overall survival or time to progression were as follows: @entity66 (P = 0.00025), @entity1 age (P = 0.04), and lag time between diagnosis and cytoreductive surgery + intraperitoneal hyperthermic perfusion (P = 0.04). Treatment-related morbidity, mortality and acute @entity137 (grade II-III) rates were 11%, 4% and 11%, respectively. Eight (89%) of 9 @entity1 had @entity843 resolution. CONCLUSION: Our results suggest that cytoreductive surgery + intraperitoneal hyperthermic perfusion is a well-tolerated, feasible and promising alternative in the management of selected @entity1 with recurrent @entity43 , but further randomized controlled studies are needed in order to confirm our findings.

title: Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion in the treatment of recurrent XXXX : a phase II clinical study.

entities_list: @entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian carcinoma', 'ovarian cancer']

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

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

entities_list: @entity902 :: ('MESH:D010984', 'Chemical') :: ['platinum']

entities_list: @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressive']

entities_list: @entity1138 :: ('MESH:D016685', 'Chemical') :: ['mitomycin C']

entities_list: @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin']

entities_list: @entity221 :: ('MESH:D005334', 'Disease') :: ['hyperthermia']

answer: @entity43 :: (MESH:D010051,Disease) :: ['epithelial ovarian cancer']


abstract: INTRODUCTION: Molecular studies about @entity189 of the oral cavity and oropharynx demonstrate the presence of @entity1 papilomavirus genome in these @entity5 , reinforcing the participation of @entity1 @entity105 . OBJECTIVES: This study aimed to determine the prevalence of @entity1 papilomavirus and genotype distribution of @entity1799 and HPV18 in oral cavity and @entity189 , as well as their association with clinical characteristics of the @entity5 . METHODS: This is a retrospective study, with clinical data collected from 82 @entity1 . @entity1 papilomavirus detection was conducted on specimens of oral cavity and @entity189 included in paraffin blocks. @entity1 were assisted in a @entity5 reference center, in the central region of Brazil, between 2005 and 2007. Polymerase chain reaction was used for the detection and genotyping of @entity1 papilomavirus. RESULTS: Among the @entity1 evaluated, 78% were male. The average age of the group was about 58 years. Risk factors, such as smoking (78%) and @entity285 consumption (70.8%) were recorded for the group. HPV DNA was detected in 21 cases (25.6%; 95% confidence interval 16.9-36.6) of which 33.3% were @entity1799 and 14.3% were HPV18. The presence of lymph node @entity3 and registered deaths were less frequent in @entity1 papilomavirus positive @entity5 , suggesting a better prognosis for these cases; however, the differences between the groups were not statistically significant. CONCLUSION: The results obtained in the present study, with respect to the presence of the high-risk @entity1799 and HPV18 genotypes, highlight the importance of @entity1 papilomavirus vaccination in the control of oral cavity and @entity189 .

title: Human papillomavirus in oral cavity and XXXX in the central region of Brazil.

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

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

entities_list: @entity189 :: ('MESH:D002277', 'Disease') :: ['carcinomas', 'oropharynx carcinomas']

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

entities_list: @entity105 :: ('MESH:D063646', 'Disease') :: ['papilomavirus in oral carcinogenesis']

answer: @entity189 :: (MESH:D002277,Disease) :: ['oropharynx carcinomas']


abstract: To better estimate how frequently @entity1 with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of @entity12320 , we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of @entity146 . Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive @entity1 , normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum @entity648 , 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. @entity146 were noted in 28%, often in the absence of @entity417 , @entity11140 , or both. Serum levels of @entity15744 and/or total @entity1255 were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive @entity1 . We conclude that @entity12320 should be considered and investigated in @entity1 with unexplained hematologic or @entity146 of the kind seen in @entity12320 , even if @entity417 , an elevated mean cell volume, a marked @entity308 of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum @entity15744 and total @entity1255 are useful as ancillary diagnostic tests in the diagnostis of @entity12320 .

title: Clinical spectrum and diagnosis of XXXX .

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

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

entities_list: @entity146 :: ('MESH:D001523', 'Disease') :: ['neuropsychiatric abnormalities', 'Neuropsychiatric abnormalities']

entities_list: @entity1255 :: ('MESH:D006710', 'Chemical') :: ['homocysteine']

entities_list: @entity648 :: ('MESH:D001663', 'Chemical') :: ['bilirubin']

entities_list: @entity11140 :: ('MESH:C564004', 'Disease') :: ['macrocytosis']

entities_list: @entity15744 :: ('MESH:D008764', 'Chemical') :: ['methylmalonic acid']

entities_list: @entity12320 :: ('MESH:C564747', 'Disease') :: ['Cbl deficiency']

answer: @entity12320 :: (MESH:C564747,Disease) :: ['cobalamin deficiency']


abstract: @entity10124 ( @entity22583 ) microspheres were tested as a parenteral delivery system for @entity1 beta-amyloid (1-42) (Abeta), a potential immunotherapeutic undergoing assessment in Phase 1 studies for @entity195 ( @entity195 ). Abeta was successfully encapsulated in PLG microspheres of average sizes of 3 or 15 microm diameter. Swiss Webster (SW) @entity19 were injected by the sub-cutaneous (s.c.) or intra-peritoneal (i.p.) routes with 3-33 microg Abeta. Abeta-PLG microparticles (3 microm) induced dose-dependent antibody responses, which were maximal at 33 microg Abeta, while Abeta in @entity1391 -buffered saline (PBS) produced weak antibody responses at the same doses by both routes. Significantly increased antibody responses were seen for both small and large particle formulations given by the i.p. route in comparison to the s.c route. It was previously reported that passive immunisation with Abeta-specific antibodies cleared amyloid plaques in a @entity19 model of @entity195 (Bard F, Cannon C, Barbour R, et al. Peripherally administered antibodies against amyloid beta-peptide enter the nervous system and reduce pathology in a @entity19 model of @entity195 . Nature Med 2000;6:916-19), an indication that induction of serum antibody is a prerequisite for efficacy.

title: Encapsulation in biodegradable microparticles enhances serum antibody response to parenterally-delivered beta-amyloid in XXXX .

entities_list: @entity1391 :: ('CHEBI:26020', 'Chemical') :: ['phosphate']

entities_list: @entity10124 :: ('CHEBI:53493', 'Chemical') :: ['Poly(lactide-co-glycolide)']

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

answer: @entity19 :: (10090,Species) :: ['mice']


abstract: BACKGROUND AND PURPOSE: More and more data point to the involvement of the @entity404   @entity1361    lymphocyte subpopulation in the pathogenesis of @entity64 . This paper attempts to answer the question of whether an increase in the percentage of @entity404   @entity1361    lymphocytes in the blood may be associated with carotid artery @entity121 ( @entity121 ). MATERIAL AND METHODS: The study involved a group of 109 @entity1 , aged 45 to 65 years, including 42 @entity1 with first-ever @entity64 , experiencing symptoms resulting from disturbances of the anterior area of cerebral circulation, arterial @entity101 and/or @entity6 (group 1). Group 2 consisted of 34 @entity1 with above-mentioned risk factors but without @entity64 . The control group comprised 33 healthy individuals. Distribution of sex and mean age was comparable. The @entity121 of carotid arteries was measured by ultrasonography. Flow cytometry was applied to determine the percentage of @entity404   @entity1361    lymphocytes in the peripheral blood. RESULTS: The @entity121 was significantly greater in @entity1 with @entity64 than in @entity1 without @entity64 . No significant correlation was found between the proportion of @entity404   @entity1361    lymphocytes in the blood and the @entity121 of carotid arteries. CONCLUSIONS: The significant proportion of @entity404   @entity1361    lymphocytes in @entity1 with @entity64 points to the involvement of the cells in the pathogenesis of @entity64 . The @entity404   @entity1361    lymphocytes are not involved in the pathomechanism of common carotid arteries @entity121 thickening in this group of @entity1 .

title: @entity404   @entity1361    lymphocytes and XXXX . Part I: @entity404   @entity1361    lymphocytes and common carotid artery @entity121 .

entities_list: @entity64 :: ('MESH:D020521', 'Disease') :: ['ischaemic stroke', 'stroke']

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

entities_list: @entity6 :: ('MESH:D003920', 'Disease') :: ['type 2 diabetes mellitus']

entities_list: @entity121 :: ('MESH:D009135', 'Disease') :: ['IMT', 'intima-media thickness']

answer: @entity64 :: (MESH:D020521,Disease) :: ['ischaemic stroke']


abstract: BACKGROUND: Coadministration of @entity10438 (MF) and @entity6410 (F) produces additive effects for improving symptoms and lung function and reduces exacerbations in @entity1 with @entity565 and @entity1030 ( @entity1030 ). The present study assessed the relative systemic exposure to MF and characterized the pharmacokinetics of MF and @entity6410 in @entity1 with @entity1030 . METHODS: This was a single-center, randomized, open-label, multiple-dose, three-period, three-treatment crossover study. The following three treatments were self-administered by @entity1 (n = 14) with moderate-to-severe @entity1030 : MF 400  g/F 10  g via a metered-dose inhaler (MF/F @entity13521 ; DULERA(  )/ZENHALE(  )) without a spacer device, MF/F @entity13521 with a spacer, or MF 400  g via a dry-powder inhaler (DPI; ASMANEX(  ) TWISTHALER(  )) twice daily for 5 days. Plasma samples for MF and @entity6410 assay were obtained predose and at prespecified time points after the last (morning) dose on day 5 of each period of the crossover. The geometric mean ratio (GMR) as a percent and the corresponding 90% confidence intervals (CI) were calculated for treatment comparisons. RESULTS: Systemic MF exposure was lower (GMR 77%; 90% CI 58, 102) following administration by MF/F @entity13521 compared to MF DPI. Additionally, least squares geometric mean systemic exposures of MF and @entity6410 were lower (GMR 72%; 90% CI 61, 84) and (GMR 62%; 90% CI 52, 74), respectively, following administration by MF/F @entity13521 in conjunction with a spacer compared to MF/F @entity13521 without a spacer. MF/F @entity13521 had a similar adverse experience profile as that seen with MF DPI. All adverse experiences were either mild or moderate in severity; no serious adverse experience was reported. CONCLUSION: Systemic MF exposures were lower following administration by MF/F @entity13521 compared with MF DPI. Additionally, systemic MF and @entity6410 exposures were lower following administration by MF/F @entity13521 with a spacer versus without a spacer. The magnitude of these differences with respect to systemic exposure was not clinically relevant.

title: Comparison of the systemic bioavailability of @entity10438 after oral inhalation from a @entity10438 / XXXX metered-dose inhaler versus a @entity10438 dry-powder inhaler in @entity1 with @entity1030 .

entities_list: @entity1030 :: ('MESH:D029424', 'Disease') :: ['chronic obstructive pulmonary disease', 'COPD']

entities_list: @entity6410 :: ('MESH:C012629', 'Chemical') :: ['formoterol', 'formoterol fumarate']

entities_list: @entity10438 :: ('MESH:C053915', 'Chemical') :: ['mometasone furoate']

answer: @entity6410 :: (MESH:C012629,Chemical) :: ['formoterol fumarate']


abstract: BACKGROUND AND PURPOSE: Treatment with @entity117 ( @entity1281 ) is established for secondary @entity64 prevention. Recent studies showed neuroprotection of @entity1281 against glutamatergic excitants. The goal of this study was to investigate the time course of neuroprotection of @entity1281 against indirect excitotoxicity by @entity519 and chemical @entity519 . METHODS: Population spike amplitude (PSA) and @entity855 content were measured in hippocampal slices from untreated control animals (c-slices) and slices prepared from animals pretreated in vivo with a single intraperitoneal injection of 20 mg/kg body wt @entity1281 1 to 48 hours before slice preparation (p-slices). RESULTS: Posthypoxic recovery of PSA was 30% in c-slices (15 minutes of @entity519 , 45 minutes of recovery). When c-slices were treated in vitro for 15 minutes with 20 mg/L @entity1281 30 minutes before @entity519 , posthypoxic recovery improved to 82 +/- 4% (mean +/- SE, P < .01). In p-slices, posthypoxic recovery of PSA improved in a time-dependent manner. With a time interval of 1 hour between in vivo pretreatment with @entity1281 and slice preparation, posthypoxic recovery of PSA was 64 +/- 16% (P < .05). With time intervals of 6 hours, 24 hours, and 48 hours, posthypoxic recovery of PSA was 87 +/- 19% (P < .01), 59 +/- 12%, and 40 +/- 9%, respectively. Pretreatment with @entity1281 in vitro or in vivo decreased the decline of @entity855 content during @entity519 and chemical @entity519 (inhibition of succinic dehydrogenase by @entity11695 ). When extracellular @entity413 was reduced to 4 mmol/L, no difference was observed between c-slices and p-slices. CONCLUSIONS: We conclude that @entity1281 is neuroprotective against @entity519 and chemical @entity519 and delays the decline of intracellular @entity855 content.

title: @entity117 increases tolerance against @entity519 and chemical XXXX .

entities_list: @entity11695 :: ('MESH:C015392', 'Chemical') :: ['3-nitropropionic acid']

entities_list: @entity117 :: ('MESH:D001241', 'Chemical') :: ['acetylsalicylic acid']

entities_list: @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxic hypoxia', 'hypoxia']

entities_list: @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']

answer: @entity519 :: (MESH:D000860,Disease) :: ['hypoxia']


abstract: Heteromerization can play an important role in regulating the activation and/or signal transduction of most forms of receptors, including receptor @entity669 kinases (RTKs). The study of receptor heteromerization has evolved extensively with the emergence of resonance energy transfer based approaches such as bioluminescence resonance energy transfer (BRET). Here, we report an adaptation of our Receptor-Heteromer Investigation Technology (Receptor-HIT) that has recently been published as the @entity24101 ( @entity24101 ) Heteromer Identification Technology ( @entity24101 -HIT). We now demonstrate the utility of this approach for investigating RTK heteromerization by examining the functional interaction between the @entity470 ( @entity470 ; also known as @entity470 / @entity470 ) and heregulin (HRG) receptor 3 ( @entity7514 ; also known as @entity7514 ) in live HEK293FT cells using recruitment of @entity10240 ( @entity10240 ) to the activated receptors. We found that @entity470 and @entity7514 heteromerize specifically as demonstrated by HRG inducing a BRET signal between @entity470 /Rluc8 and @entity10240 /Venus only when @entity7514 was co-expressed. Similarly, EGF stimulation promoted a specific BRET signal between @entity7514 /Rluc8 and @entity10240 /Venus only when @entity470 was co-expressed. Both EGF and HRG effects on @entity10240 interaction are dose-dependent, and specifically blocked by @entity470 inhibitor @entity20830 . Furthermore, truncation of @entity7514 to remove the putative @entity10240 binding sites appears to abolish EGF-induced @entity10240 recruitment to the @entity41410 heteromer. Our results support the concept that @entity470 interacts with @entity10240 in both constitutive and EGF-dependent manners and this interaction is independent of @entity7514 co-expression. In contrast, @entity7514 - @entity10240 interaction requires the heteromerization between @entity470 and @entity7514 . These findings clearly indicate the importance of @entity470 - @entity7514 heteromerization in @entity7514 -mediated @entity10240 -dependent signaling pathways and supports the central role of @entity7514 in the diversity and regulation of HER family functioning.

title: Profiling @entity470 and heregulin receptor 3 heteromerization using receptor XXXX kinase heteromer investigation technology.

entities_list: @entity24101 :: ('10663', 'Gene') :: ['G protein-coupled receptor', 'GPCR']

entities_list: @entity470 :: ('1956', 'Gene') :: ['erbB1', 'EGFR', 'HER1', 'epidermal growth factor (EGF) receptor']

entities_list: @entity10240 :: ('2885', 'Gene') :: ['Grb2', 'growth factor receptor-bound protein 2']

entities_list: @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine']

answer: @entity669 :: (CHEBI:18186,Chemical) :: ['tyrosine']


abstract: PURPOSE: Demonstrate that the blockade of angiotensin II AT-1 receptors, through the systemic administration of @entity9885 , can reduce the @entity23865 expression and the resulting macrophage accumulation in the @entity3193 of @entity753 @entity95 . METHODS: Thirty-two @entity95 were divided into 3 groups: group I (GI) was fed a standard @entity95 diet; group II (GII) was fed a @entity753 diet; and group III (GIII) was fed a @entity753 diet plus @entity9885 . Serum levels of total @entity165 , @entity412 , HDL @entity165 , and blood @entity413 were determined in fasting @entity95 at the beginning of the experiment and on the day of euthanasia. The @entity3193 were submitted to morphometric analysis as well as immunohistochemical analysis with @entity23865 and RAM-11 (macrophage marker) antibodies. RESULTS: No abnormality was detected in GI. Group II and III had significant increases in @entity3193 complex thicknesses when compared with group I (P<0.001). GII showed a significant increase in immunoreactivity for @entity23865 in relation to GI (P=0.001) and GIII (P=0.004). GII showed a significant increase in immunoreactivity for RAM-11 of the @entity3193 complex in relation to GI (P<0.001) and GIII (P=0.034). A significant increase in immunoreactivity for RAM-11 was observed in GIII in relation to GI (P=0.008). CONCLUSION: @entity9885 reduced the @entity23865 expression and the resultant macrophage accumulation in the @entity3193 @entity95 .

title: Effect of XXXX on leukocyte recruitment in @entity3193 complex in hypercholesterolemia model.

entities_list: @entity753 :: ('OMIM:143890', 'Disease') :: ['hypercholesterolemic']

entities_list: @entity95 :: ('9986', 'Species') :: ['rabbits', 'rabbit', 'New Zealand rabbits']

entities_list: @entity9885 :: ('MESH:C437965', 'Chemical') :: ['olmesartan', 'Olmesartan']

entities_list: @entity412 :: ('CHEBI:17855', 'Chemical') :: ['triglyceride']

entities_list: @entity3193 :: ('MESH:D015862', 'Disease') :: ['choroid-sclera', 'choroid-sclera complex of hypercholesterolemic', 'choroid and sclera']

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

answer: @entity9885 :: (MESH:C437965,Chemical) :: ['olmesartan']


abstract: Periodically in the history of @entity101 therapy there have been minor storms that have significantly affected the utilization of entire classes of agents. The first storm struck with the case-control studies suggesting that @entity2515 was associated with an increased risk of @entity0 , a claim subsequently disproved by a number of other studies. The second storm was initiated by a subanalysis of the Multiple Risk Factor Intervention Trial (MRFIT), from which it was inferred that, in a subset of @entity101 @entity1 , diuretic treatment may have been harmful rather than beneficial. Despite this claim and other speculations, diuretics-especially at low doses-remain a gold standard of antihypertensive therapy. Recently, a third storm has developed in the field of antihypertensive therapy: a case-control study report and a non-randomized cohort study have questioned the use of @entity460 channel blockers in @entity101 . The case-control study suffers from the limitations inherent in this study design, which often gives rise to conflicts and contradiction. In fact, another case-control study published in 1995 reached exactly the opposite conclusions and claimed that @entity460 channel blockers were associated with significantly less @entity583 than traditional antihypertensive therapy. A meta-analysis was also presented as supporting the non-randomized studies questioning the safety of @entity460 channel blockers. However, it refers to @entity1 with @entity301 , not to @entity1 with @entity101 , and also combined studies performed with different aims, and data from short-term and long-term studies using short-acting formulations of @entity460 channel blockers. The controversies generated by these reports have gone well beyond their scientific merit. For final judgement we should wait for well-designed prospective studies, several of which are under way. For the time being, there is no reason to change the current practice of antihypertensive therapy, as summarized in the recommendations of both the United States Joint National Committee and the World Health Organization/International Society of @entity101 Committee, that is, diuretics and beta-blockers are among those antihypertensive agents with clearly proven benefits in mortality-morbidity studies, but @entity460 channel blockers as well as ACE inhibitors and alpha-blockers can also be used profitably in the treatment of @entity101 .

title: The XXXX channel blocker controversy in perspective.

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

entities_list: @entity0 :: ('MESH:D001943', 'Disease') :: ['carcinoma of the breast']

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

entities_list: @entity301 :: ('MESH:D003327', 'Disease') :: ['coronary heart disease']

entities_list: @entity2515 :: ('MESH:D012110', 'Chemical') :: ['reserpine']

entities_list: @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium']

entities_list: @entity583 :: ('MESH:D009203', 'Disease') :: ['myocardial infarction']

answer: @entity460 :: (MESH:D002118,Chemical) :: ['calcium']


abstract: In @entity1 aging is a complex process that determines many physical and metabolic alterations correlated to the accumulation of oxidative damage in different tissues. @entity6288 is an age-related nonpathological condition that includes a progressive loss of mass and strength in skeletal muscle, associated with a decline in the fibers' functional capability. This condition could be correlated to abnormal reactive @entity26 species (ROS) accumulation with consequent fiber oxidative damage. This complex situation is not only evident in mature muscle fibers but also in muscle resident satellite cells (involved in fiber damage repairing) in which some functional parameters, at least for that concerns the @entity141 homeostasis, seem to be modified. In fact, our data show that there is an age-dependent increase of lipid peroxidation, in cultured myotubes (differentiated and fused satellite cells) after 7 days of in vitro differentiation. In these substrates also the capacity of these cells to produce @entity141 transient in response to various stimuli ( @entity855 , @entity5834 , @entity1239 , @entity4338 ) is, sometimes, drastically modified. In particular, the presence of an age-dependent defective status of excitation-contraction (EC) coupling apparatus is supported by a single cell @entity141 analysis obtained from myotubes (derived from aged muscles) in the presence of 40 mM @entity5834 or 40 mM @entity4338 . The alkaloid presence induces a complete emptying of @entity8452 -dependent @entity460 stores indicating a probable integrity both of SR-terminal cisternae and/or the specific @entity141 channel known as @entity13868 . However, if a sarcolemmal depolarization is induced by the addition of 40 mM @entity4338 in the experimental medium then @entity141 release @entity13868 -dependent can be observed only if @entity141 is present in the experimental solution. These results suggest that the EC uncoupling status could be due to the alteration of the interaction between @entity13868 and @entity38020 . The two receptors are present and functionally active in myotubes from aged donors but they are probably still not in the right localization. These results suggest that during donor's life the satellite cells undergo an aging process similar to the one observed in skeletal muscle tissue, even if they are in a quiescence status for most of the time.

title: Age-dependent effects on functional aspects in XXXX satellite cells.

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

entities_list: @entity1239 :: ('MESH:D009538', 'Chemical') :: ['nicotine']

entities_list: @entity5834 :: ('MESH:D002110', 'Chemical') :: ['caffeine']

entities_list: @entity8452 :: ('MESH:D012433', 'Chemical') :: ['ryanodine']

entities_list: @entity6288 :: ('MESH:D055948', 'Disease') :: ['Sarcopenia']

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


abstract: The @entity1963 @entity35 is considered to be an animal model of @entity1963 . The mutants had a long constricted segment (from distal ileum to rectum) below the dilated distal ileum. In the dilated region, synaptophysin-immunoreactivity (IR) was almost preserved in all layers of the intestinal wall. In the constricted distal ileum and oral proximal colon, synaptophysin-IR was scarce in all layers, including the circular and longitudinal muscle layers. In the anal proximal and distal colon, synaptophysin-IR was almost scarce in the @entity121 ( @entity121 ). An ultrastructural study confirmed that almost no terminals were found in the @entity121 of any regions of constricted intestine. Therefore, the @entity121 in any region of a constricted segment, is presumed to be poor innervation. However, a few synaptophysin-IR were found in the longitudinal muscle layer (LML) of an anal part of a constricted segment. An ultrastructural study also confirmed that some terminals were observed in the LML of this segment. The present study suggested that denervated @entity121 is related to the production of constricted segment, irrespective of the presence or absence of terminals in the LML.

title: Distribution of peripheral nerve terminals in the small and large intestine of @entity1963 @entity35 ( XXXX @entity35 ).

entities_list: @entity1963 :: ('MESH:D006627', 'Disease') :: ["Hirschsprung's disease", 'congenital aganglionosis']

entities_list: @entity121 :: ('MESH:D009135', 'Disease') :: ['CML', 'circular muscle layer']

answer: @entity1963 :: (MESH:D006627,Disease) :: ['Hirschsprung's disease']


abstract: UNASSIGNED: Diet is an important variable in toxicology. There are mixed reports on the impact of soy components on energy utilization, fat deposition, and reproductive parameters. Three generations of @entity2659 @entity19 were fed irradiated natural ingredient diets with varying levels of soy (NIH-41, 5K96, or 5008/5001), purified irradiated AIN-93 diet, or the AIN-93 formulation modified with @entity1068 -washed soy protein concentrate (SPC) or SPC with @entity6400 (SPC-IF). NIH-41 was the control for pairwise comparisons. Minimal differences were observed among natural ingredient diet groups. F0 males fed AIN-93, SPC, and SPC-IF diets had elevated @entity413 levels and lower insulin levels compared with the NIH-41 group. In both sexes of the F1 and F2 generations, the SPC and SPC-IF groups had lower body weight gains than the NIH-41 controls and the AIN-93 group had an increased percent body fat at postnatal day 21. AIN-93 F1 pups had higher baseline @entity413 than NIH-41 controls, but diet did not significantly affect breeding performance or responses to @entity413 or uterotrophic challenges. Reduced testes weight and sperm in the AIN-93 group may be related to low @entity9138 levels. Our observations underline the importance of careful selection, manufacturing procedures, and nutritional characterization of diets used in toxicological studies.

title: Comparison of endpoints relevant to toxicity assessments in 3 generations of @entity2659 XXXX fed irradiated natural and purified ingredient diets with varying soy protein and isoflavone contents.

entities_list: @entity6400 :: ('MESH:D007529', 'Chemical') :: ['isoflavones']

entities_list: @entity9138 :: ('MESH:D013831', 'Chemical') :: ['thiamine']

entities_list: @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']

answer: @entity19 :: (10090,Species) :: ['mice']


abstract: In 14 @entity1 with @entity583 (M.I.) not having any other disease, the possible quantitative relationship between enzymes from M.I. and changes in concentration of acute phase reactants coming from the liver were studied. The @entity1 were followed up until 1 1/2 years after M.I. and comparison of baseline-protein values took place using a control group of 18 healthy individuals. Quantitation of protein changes was done by planimetric determination of the area under the concentration curve and by taking peak values. The @entity583 was quantitatively estimated by mathematical analysis of the time course of @entity27216 dehydrogenase (alpha-HBDH) plasma concentrations and by taking peak values. A quantitative relationship with enzymatic @entity1188 size was found for haptoglobin, @entity6927 -acid glycoprotein, @entity6927 -antitrypsin, @entity1851 , @entity2002 and E.S.R. Albumin and @entity69 did not show a negative quantitative relationship with enzymatic @entity1188 size. Humoral factors originating from the site of tissue injury and evoking in proportion a positive acute phase reaction by the liver are probably the basis for this observed quantitative relationship.

title: Acute-phase proteins from the liver and enzymes from XXXX ; a quantitative relationship.

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

entities_list: @entity27216 :: ('MESH:C031570', 'Chemical') :: ['alpha-hydroxybutyrate']

entities_list: @entity583 :: ('MESH:D009203', 'Disease') :: ['myocardial infarction', 'acute myocardial infarction']

entities_list: @entity1851 :: ('1401', 'Gene') :: ['C-reactive protein']

answer: @entity583 :: (MESH:D009203,Disease) :: ['myocardial infarction']


abstract: Among a number of tissues and peripheral blood cells in @entity1573 , leukocytes, bone marrow cells, liver and spleen showed high @entity857 -ribosyltransferase activity, with leukocytes having the highest. Density gradient centrifugation of the leukocytes revealed that the leukocyte @entity857 -ribosyltransferase originates in the polymorphonuclear cells, so called heterophils. Subcellular distribution of the cells showed the localization of the enzyme in the granule fraction. Based on the obtained @entity535 sequences of @entity369 -specific @entity857 -ribosyltransferase purified from @entity1573 peripheral heterophils, two @entity369 -specific @entity857 -ribosyltransferase cDNAs (designated @entity19790 and @entity19791 ) were obtained from @entity1573 bone marrow cells. Each cDNA encodes a different peptide of 312 @entity535 residues. Homology of the deduced @entity535 sequences between @entity19790 and @entity19791 was 78.3%. @entity369 -specific @entity857 -ribosyltransferase activity was detected in culture medium of COS 7 cells transiently transfected with @entity19790 cDNA, while activity from the cells transfected with @entity19791 cDNA was found in both culture medium and cell lysate. @entity19790 transferase required @entity6514 ( @entity5067 ) for the activity and in the presence of @entity1219 , the activity was inhibited while the @entity19791 enzyme was activated by either agent. Highly conserved regions were observed among the deduced @entity535 sequences of @entity19790 , @entity19791 , @entity1573 erythroblast and @entity95 and @entity1 skeletal muscle @entity857 -ribosyltransferases, and rodent T-cell surface antigen RT6. Two forms of the transferase with much the same properties as @entity19790 and @entity19791 proteins, regarding the effect of @entity1219 and @entity5067 , were detected in bone marrow cells. Based on these results it seems that @entity19790 and @entity19791 cDNAs encode the two forms of @entity369 -specific @entity857 -ribosyltransferase detected in @entity1573 bone marrow cells.

title: Molecular cloning and characterization of @entity369 -specific @entity857 -ribosyltransferases from XXXX bone marrow cells.

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

entities_list: @entity6514 :: ('MESH:D008623', 'Chemical') :: ['2-mercaptoethanol']

entities_list: @entity369 :: ('CHEBI:29016', 'Chemical') :: ['arginine', 'Arginine']

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


abstract: AIMS: This study aimed to determine whether (a) there was an imbalance between @entity11799 ( @entity11799 ) and @entity11800 ( @entity11800 ) after cardiopulmonary resuscitation (CPR) in a @entity235 model of prolonged @entity2224 ( @entity2224 ); (b) with the duration of @entity2224 , the degree of the imbalance would be greater; and (c) there was a relationship between the level of @entity11799 or @entity11800 and the cardiac function. METHODS AND RESULTS: @entity2224 was electrically induced in 24 @entity235 . The animals were randomly divided into 3 groups (sham control, n = 8; 8-minute @entity2224 , n = 8; 12-minute @entity2224 , n = 8). Echocardiographic measurement and hemodynamic variables were recorded before @entity2224 and after return of spontaneous circulation. @entity11800 ( @entity11800 ) and @entity11799 were analyzed by Western blot and immunohistochemistry. Compared with sham controls, @entity235 under @entity2224 and CPR showed significantly decreased level of @entity11800 (P < .001), and with the duration of @entity2224 , the level of @entity11800 declined (P < .01). The level of @entity11799 did not achieve statistical significance in the 3 groups (P > .05); however, they were higher in @entity2224 and longer duration @entity2224 groups. The ratios of @entity11800 / @entity11799 were lower in @entity2224 groups (P < .05). There was a negative correlation between @entity11800 and left atrium dimension and left ventricular diastolic dimensions (r = -0.83 and r = -0.96, respectively; P < .01) and a positive correlation between @entity11800 and left ventricular ejection fraction (r = 0.85; P < .01). CONCLUSIONS: There was an imbalance between @entity11800 and @entity11799 after CPR. It may partly contribute to the postresuscitation @entity299 .

title: Imbalance between @entity11800 and XXXX after cardiopulmonary resuscitation.

entities_list: @entity11800 :: ('403816(Tax:9615)', 'Gene') :: ['tissue inhibitor of metalloproteinase 1', 'TIMP-1', 'Tissue inhibitor of metalloproteinase 1']

entities_list: @entity2224 :: ('MESH:D014693', 'Disease') :: ['VF', 'ventricular fibrillation', 'Ventricular fibrillation']

entities_list: @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac dysfunction']

answer: @entity11799 :: (403885(Tax:9615),Gene) :: ['matrix metalloproteinase 9']


abstract: PURPOSE: To evaluate the usefulness of routine blood cultures in @entity1 who develop temperatures of 38.5 degrees C or higher while treated with @entity1199 ( @entity1199 ). METHODS: Retrospective chart review study. Charts of @entity1 treated with high-dose @entity1199 or biochemotherapy for metastatic @entity320 were reviewed at the University of Louisville from 2005 to 2007. The study objective was to estimate the frequency of @entity1503 . RESULTS: A total of 205 blood cultures in 46 @entity1 (27 male, 19 female) were reviewed. The average age was 53 years (25-71 years). The @entity1 had an average of 3 cycles of therapy. The mean temperature of the febrile episodes was 38.7 degrees C. The mean absolute neutrophil count was 5.1 K/microL. Of these 205 febrile episodes, only 1 blood culture was true positive. The @entity1 had methicillin sensitive @entity794 @entity2259 . There were 5 false positive blood cultures. Four hundred thirty-four further febrile episodes were documented without blood cultures drawn. None of these @entity1 were found to be infected. The yield of true positive blood cultures in this setting was 0.5% (0%-3%, CI). There was, however, a higher number of false positive blood cultures, 2.4% (0.5%-4.5%, CI). CONCLUSIONS: Blood cultures during @entity1199 containing therapy are very inefficient to differentiate between infections versus @entity1199 -related fever.

title: Obtaining routine blood cultures during XXXX -containing therapy is unnecessary.

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

entities_list: @entity794 :: ('1280', 'Species') :: ['staphylococcus aureus']

entities_list: @entity1503 :: ('MESH:D006402', 'Disease') :: ['true and false positive blood cultures']

entities_list: @entity2259 :: ('MESH:D016470', 'Disease') :: ['bacteremia']

entities_list: @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma']

answer: @entity1199 :: (3558,Gene) :: ['interleukin-2']


abstract: BACKGROUND: The aim of the treatment of @entity2012 is to normalise the hormonal activity. Besides the surgical and radiation treatment, medical therapy can be used. The project was set to determine the value of combined therapy with @entity18245 and @entity19266 in @entity1 with active @entity2012 . METHODS AND RESULTS: Nine @entity1 previously treated with @entity18245 for at least one year without normalisation of hormonal activity were included in the study. @entity19266 was added to @entity18245 for one month. The combined treatment brought about reduction of @entity2124 ( @entity2124 ) levels, however, with marginal significance only. @entity9045 , @entity442 and @entity2301 serum levels were not changed significantly. Considering the individual cases, the combined treatment resulted in normalisation of @entity2124 levels in one @entity1 and that of @entity442 in another one. Substantial decrease of @entity2124 levels (> 50%) was found in three @entity1 and that of @entity442 (> 20%) in another one @entity1 . CONCLUSIONS: The combined treatment of @entity2012 appears to be more effective than monotherapy with @entity18245 only in a subset of acromegalic @entity1 .

title: [Combined therapy of @entity2012 with a combination of @entity18245 and XXXX ].

entities_list: @entity19266 :: ('MESH:C006208', 'Chemical') :: ['terguride', 'Terguride']

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

entities_list: @entity18245 :: ('MESH:C060347', 'Chemical') :: ['lanreotide']

answer: @entity19266 :: (MESH:C006208,Chemical) :: ['terguride']


abstract: @entity717 ( @entity717 ) is a controversial procedure with reported inconsistent results. We reviewed 50 @entity1 (60 @entity572 ) who underwent this procedure for extensive @entity2530 of the femoral head, focusing on varization to determine its effectiveness as a head-preserving procedure in young adults. The mean age of the @entity1 was 28 years (range, 18-46 years). Using the Ficat-Arlet classification, 40 @entity572 had Stage II and 20 @entity572 had Stage III involvement. According to the classification system of Shimizu et al., the extent of the lesions were Grade C in 54 @entity572 and Grade B in six @entity572 ; the location of the lesions were Grade c in 56 @entity572 and Grade b in four @entity572 . Minimum followup was 18 months (mean, 84 months; range, 18-156 months). The mean preoperative Harris hip score was 44.7 points (range, 32-62 points) which improved to an average postoperative score of 80.1 points (range, 44-100 points) at the latest followup. Forty-four @entity572 showed no radiographic evidence of progression of collapse. Ten @entity572 showed progressive collapse, seven @entity572 showed progressive @entity85 , three @entity572 had @entity2249 , and one hip had @entity281 . We believe @entity717 with varization is worth attempting for extensive @entity2530 of the femoral head in young adults, although failures and complications are not uncommon. LEVEL OF EVIDENCE: Level IV, case series. See the Guidelines for Authors for a complete description of levels of evidence.

title: XXXX for nontraumatic @entity2530 of the femoral head in young adults.

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

entities_list: @entity2249 :: ('MESH:D005265', 'Disease') :: ['stress fractures of the femoral neck']

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

entities_list: @entity717 :: ('MESH:D009069', 'Disease') :: ['Transtrochanteric rotational osteotomy', 'TRO']

entities_list: @entity85 :: ('MESH:D009140', 'Disease') :: ['varus deformity']

entities_list: @entity2530 :: ('MESH:D010020', 'Disease') :: ['osteonecrosis']

answer: @entity717 :: (MESH:D009069,Disease) :: ['Transtrochanteric rotational osteotomy']


abstract: UNASSIGNED: Amyloid - b (Ab) oligomers are recognized as the primary @entity2359 in @entity195 ( @entity195 ). Impaired brain energy metabolism and oxidative stress are implicated in @entity73 in @entity195 . @entity2125 ( @entity2125 ), a coenzyme involved in redox activities in the mitochondrial electron transport chain, has been identified as a key regulator of the lifespan-extending effects, and the activation of @entity2125 expression has been linked with a decrease in Ab @entity137 in @entity195 . One of the key precursors of @entity2125 is @entity13908 ( @entity6532 ), a product of the @entity4571 phosphoribosyltransferase reaction. To determine whether improving brain energy metabolism will forestall disease progress in @entity195 , the impact of the @entity2125 precursor @entity6532 on Ab oligomer - induced @entity528 and @entity73 were studied in organotypic hippocampal slice cultures (OHCs) and in a @entity35 model of @entity195 . Treatment of intracerebroventricular Ab oligomer infusion @entity195 model @entity35 with @entity6532 (500mg/kg, intraperitoneally) sustained improvement in cognitive function as assessed by the Morris water maze. In OHCs, Ab oligomer- treated culture media with @entity6532 attenuated neuronal cell death. @entity6532 treatment also significantly prevented the Ab oligomer-induced inhibition of LTP. Furthermore, @entity6532 restored levels of @entity2125 and @entity855 , eliminated accumulation of reactive @entity26 species (ROS) in the Ab oligomer - treated hippocampal slices. All these protective effects were reversed by @entity8250 , which generates inactive @entity2125 . The present study indicates that @entity6532 could restore cognition in @entity195 model @entity35 . The beneficial effect of @entity6532 is produced by ameliorating neuron survival, improving energy metabolism and reducing ROS accumulation. These results suggest that @entity6532 may become a promising therapeutic drug for @entity195 .

title: @entity13908 protects against b-amyloid oligomer - induced @entity73 and XXXX .

entities_list: @entity2125 :: ('MESH:D009243', 'Chemical') :: ['NAD(+)', 'Nicotinamide adenine dinucleotide']

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

entities_list: @entity8250 :: ('MESH:C010835', 'Chemical') :: ['3-acetylpyridine']

entities_list: @entity73 :: ('MESH:D003072', 'Disease') :: ['cognitive impairment', 'cognitive decline']

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

entities_list: @entity13908 :: ('MESH:D009537', 'Chemical') :: ['nicotinamide mononucleotide']

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

entities_list: @entity4571 :: ('MESH:D009536', 'Chemical') :: ['nicotinamide']

entities_list: @entity528 :: ('MESH:D009410', 'Disease') :: ['neuronal death']

entities_list: @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxic agents']

answer: @entity528 :: (MESH:D009410,Disease) :: ['neuronal death']


abstract: INTRODUCTION: The purpose of this study was to assess the medium-term results of reconstruction of the extensor mechanism using the medial gastrocnemius while also providing soft tissue coverage. MATERIALS AND METHODS: This retrospective review consisted of a consecutive series of four @entity1 (age 28-40 years) with complex high energy @entity130 to lower extremity including both soft tissue loss and disruption of the knee extensor mechanism. The medial gastrocnemius rotational @entity1912 was used to reconstruct the patellar tendon and restore soft tissue coverage simultaneously. Range of motion and extensor lag; functional recovery was judged by return to work and sports activity. Validated measures included the Oxford Knee Score, Knee @entity130 Outcome Score, and the modified Cincinnati Score. RESULTS: At the final follow up was 61.5 (57-66) months after reconstruction, the mean SF 12 physical component score ranged from 21.7 to 56.8 with a median of 55.3; the mental component from 42.8 to 60.7 with a median of 58.6. The KSS knee score ranged from 50 to 78 with a median of 68; the function score from 65 to 90 with a median of 85. The Oxford knee score ranged from 22 to 45 with a median of 33.5. The KOOS ranged from 28 to 82.7 with a median of 73.7 and the modified Cincinnati score from 38 to 82 with a median of 76.5. Knee range of motion ranged from 0 to 120  . Of the four @entity1 three returned to working fulltime in their profession and returned to sports, including mountain biking and fitness training. CONCLUSIONS: For severe traumatic @entity3331 with the combination of soft tissue defects and disruption of the extensor mechanism, the medial gastrocnemius @entity1912 provides an excellent reconstructive option to address both problems simultaneously. The results of this small case series support the use of this limb salvage technique.

title: Medial Gastrocnemius XXXX for Reconstruction of the Extensor Mechanism of the Knee Following High-Energy @entity130 . A minimum 5 year follow-up.

entities_list: @entity3331 :: ('MESH:D007718', 'Disease') :: ['knee injuries']

entities_list: @entity130 :: ('MESH:D014947', 'Disease') :: ['traumatic injuries', 'Injury and Osteoarthritis']

answer: @entity1912 :: (241,Gene) :: ['Flap']


abstract: BACKGROUND: The margin zone in spreading psoriatic lesions has frequently been used as a model to study the changes in epidermal proliferation, keratinization and @entity32 during the transition from symptomless to lesional skin. However, the dynamics of the changes in the epidermal subpopulations-basal cells, transit amplifying cells and differentiated cells-have not been studied in the transition between symptomless and lesional skin. OBJECTIVES: To quantify in a dynamic model of the margin zone in @entity1569 the characteristics of these subpopulations with respect to epidermal proliferation and differentiation. METHODS: From seven @entity1 with active @entity1569 , biopsies were taken from the distant uninvolved skin, outer margin, inner margin and centre of a spreading @entity5144 . Frozen sections were labelled immunofluorescently using direct immunofluorescence for Ki-67 and @entity2393 and the Zenon labelling technique for keratin 6, 10 and 15. Digital photographs of the stained sections were quantitatively analysed. RESULTS: In the distant uninvolved skin the expression of @entity2393 was decreased and keratin 15 expression was lost. In this area suprabasal cells expressed @entity2393 and in the outer margin suprabasal cells expressed Ki-67. From the outer to the inner margin of the @entity1569 plaque, which coincided with the appearance of the clinical lesion, there was a significant change in the various markers. The patchy expression of keratin 6 in the inner margin became homogeneous in the centre of the @entity1569 plaque and here was also coexpression of @entity7434 in a single cell. CONCLUSIONS: The present study provides additional evidence that the distant uninvolved skin has a prepsoriatic phenotype, which is the first step in a psoriatic cascade. The cascade between symptomless and lesional skin comprises first an @entity32 with involvement of @entity2393 -dim cells (transit amplifying cells) subsequently eliciting an enlarged germinative compartment with increased recruitment of cycling epidermal cells and focal expression of proliferation-associated keratins, ultimately culminating in a more-or-less homogeneous epidermis with massive recruitment of cycling epidermal cells and proliferation-associated keratinization.

title: Assessment of epidermal subpopulations and proliferation in healthy skin, symptomless and lesional skin of spreading XXXX .

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

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

entities_list: @entity1569 :: ('MESH:D011565', 'Disease') :: ['psoriasis']

entities_list: @entity5144 :: ('MESH:D015535', 'Disease') :: ['psoriatic plaque']

entities_list: @entity7434 :: ('3858', 'Gene') :: ['keratin 6 and keratin 10']

answer: @entity1569 :: (MESH:D011565,Disease) :: ['psoriasis']


abstract: The interrelations between @entity251 , insulin and @entity2493 levels in males with @entity209 ( @entity209 ) are still not clarified, especially in young age groups. The aim of the present study was to compare the @entity251 serum levels in young @entity1 with @entity209 to those in healthy controls, and to determine the possible changes in their @entity2493 rhythm, as well as the relation between @entity2493 , insulin and lipid profile. Fasting insulin and @entity251 concentrations were measured in 10 healthy nonobese and 10 @entity209 @entity1 . Blood samples for @entity2493 , insulin and luteinizing hormone (LH) were collected at 19.00, 03.00 and 11.00 hours. A significant difference was found between the @entity251 levels in controls and @entity1 . Luteinizing hormone levels in both groups were similar, however, higher night LH levels in @entity209 @entity1 were observed. No changes in the @entity2493 concentrations of the two groups were found. In conclusion, total @entity251 levels were significantly lower in young @entity1 with @entity209 compared with healthy age-matched controls. Mild hypoandrogenia in hyperinsulinaemic @entity1 was not related with changes in their @entity2493 levels. No alterations in the endogenous @entity2493 rhythm of the @entity209 @entity1 were found.

title: Low @entity251 levels and unimpaired @entity2493 secretion in young males with XXXX .

entities_list: @entity2493 :: ('MESH:D008550', 'Chemical') :: ['melatonin']

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

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

entities_list: @entity209 :: ('MESH:D008659', 'Disease') :: ['MS', 'metabolic syndrome']

answer: @entity209 :: (MESH:D008659,Disease) :: ['metabolic syndrome']


abstract: BACKGROUND: @entity171 have been shown to be effective agents in the treatment of @entity170 . Because corticosteroid associated @entity170 is often associated with @entity79 , the effect of intermittent intravenous infusions of @entity5279 on this condition has been investigated. METHODS: Seventeen @entity1 (five male) with chronic @entity358 (15 @entity565 , two @entity370 ) were treated with infusions of 30 mg @entity5279 once every three months for one year. These @entity1 had been taking an average of 14 (range 7.5-40) mg prednisolone a day for an average of 14 (range 3-30) years. Bone density measurements, by dual energy x ray absorptiometry, and radiography of the dorsolumbar spine were carried out before and one year after treatment. Bone formation was assessed by measurement of serum alkaline phosphatase and bone resorption by measurement of the fasting urinary @entity720 : @entity1011 ratio at the same time as densitometry and radiography were performed. RESULTS: Pretreatment density of @entity2586 and the neck of the femur was significantly lower in these @entity1 compared with a cohort of 100 age and sex matched controls ( @entity2586 (mean (SEM)): 0.906 (0.050) g/cm2 v 1.142 (0.016) g/cm2; neck of femur: 0.793 (0.030) g/cm2 v 0.936 (0.013)) g/cm2. After treatment there was a significant fall in serum alkaline phosphatase activity from (mean (SEM)) 220 (16) U/1 to 174 (9) U/1 (normal 80-280 U/1) and in the fasting urinary @entity720 : @entity1011 ratio from (mean (SEM) 0.040 (0.006) to 0.024 (0.003) (normal < 0.033). A significant rise was noted in @entity2586 density to 0.927 (0.047) g/cm2; mean rise of 3.4%). No change was noted in density of the neck of the femur. CONCLUSIONS: Intermittent infusions of intravenous @entity5279 would seem to be effective in both reducing turnover of bone and increasing bone density in corticosteroid induced @entity170 associated with @entity1030 . Longer term controlled studies are indicated.

title: Intravenous @entity5279 in the treatment of XXXX associated with @entity358 : an open pilot study.

entities_list: @entity171 :: ('MESH:D004164', 'Chemical') :: ['Bisphosphonates']

entities_list: @entity5279 :: ('MESH:C019248', 'Chemical') :: ['pamidronate']

entities_list: @entity170 :: ('MESH:D010024', 'Disease') :: ['postmenopausal osteoporosis', 'osteoporosis']

entities_list: @entity79 :: ('MESH:D001847', 'Disease') :: ['increased bone turnover']

entities_list: @entity358 :: ('MESH:D008171', 'Disease') :: ['corticosteroid dependent lung disease']

entities_list: @entity720 :: ('CHEBI:18095', 'Chemical') :: ['hydroxyproline']

entities_list: @entity1030 :: ('MESH:D029424', 'Disease') :: ['chronic lung disease']

entities_list: @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine']

entities_list: @entity370 :: ('MESH:D012507', 'Disease') :: ['sarcoidosis']

answer: @entity170 :: (MESH:D010024,Disease) :: ['osteoporosis']


abstract: @entity8778 ( @entity8778 ;) is a @entity10043 analogue with clinical activity against @entity5734 , @entity1072 and @entity706 . To clarify the @entity137 profiles of @entity8778 , we conducted a phase I and pharmacological study of @entity8778 with a schedule of seven-day continuous intravenous infusion every 28 days up to a maximum of three cycles. We enrolled 10 previously-treated @entity1 with various @entity706 . No dose-limiting @entity137 (grade 4 hematologic and/or grade 3 or more non-hematologic) was observed in the three @entity1 who received 0.06 mg/kg/day (Level 1). Of the seven @entity1 who received 0.09 mg/kg/day (Level 2), one @entity1 developed grade 4 @entity519 and grade 4 @entity882 , and another developed grade 4 @entity1398 . Of the seven @entity1 treated at Level 2, one with @entity784 attained complete remission, and one with @entity1073 , one with @entity1072 and one with @entity6494 attained partial remission. A pharmacokinetic analysis of the seven @entity1 without @entity1778 cells showed that their area under the concentration versus time curves of plasma @entity8778 increased dose-dependently from 2661.3 +/- 300.4 nM x h at Level 1 (n = 3) to 3411.3 +/- 341.0 nM x h at Level 2 (n = 4) (P = 0.034). We conclude that the recommended phase II dose of @entity8778 (0.09 mg/kg/day as a seven-day continuous i.v. infusion) in Caucasian @entity1 can be safely administered to Japanese @entity1 . The encouraging results prompted us to plan subsequent phase II studies of @entity8778 against @entity6494 , @entity5734 and @entity706 .

title: Phase I study of XXXX ( @entity8778 ) in @entity706 . @entity8778 Study Group.

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

entities_list: @entity8778 :: ('MESH:D017338', 'Chemical') :: ['Cladribine', 'cladribine', '2-chlorodeoxyadenosine']

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

entities_list: @entity706 :: ('MESH:D008223', 'Disease') :: ['indolent lymphoma', 'lymphoid malignancies']

entities_list: @entity882 :: ('MESH:D013921', 'Disease') :: ['thrombocytopenia']

entities_list: @entity5734 :: ('MESH:D007943', 'Disease') :: ['hairy cell leukemia']

entities_list: @entity784 :: ('MESH:D016399', 'Disease') :: ['cutaneous T-cell lymphoma']

entities_list: @entity1072 :: ('MESH:D015451', 'Disease') :: ['chronic lymphocytic leukemia']

entities_list: @entity6494 :: ('MESH:D015459', 'Disease') :: ['adult T-cell leukemia-lymphoma']

entities_list: @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxemia']

entities_list: @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia']

entities_list: @entity1073 :: ('MESH:D020522', 'Disease') :: ['mantle cell lymphoma']

answer: @entity8778 :: (MESH:D017338,Chemical) :: ['cladribine']


abstract: Skin @entity82 is involved in several pathologies as @entity2805 or @entity2631 . The determination of the mechanisms at the origin of these problems is however difficult due to the low number of in vivo models. To bypass this absence of animal models, studies typically use @entity1 pathological cells cultured in a monolayer way on plastic. However, cell behavior is different according to the fact that cells are on plastic or embedded in matrix. Using a tissue engineering method, we have developed new in vitro models to study these pathologies of the skin. @entity1 pathological cells are used to reconstitute a three dimensional fibrotic tissue comprising the dermal and the epidermal parts of the skin. This method is called the self-assembly approach and is based on the cell capacity to reconstitute in vitro their own environment as in vivo. In this chapter, protocols generating reconstructed pathological skin using this approach are detailed. The methods include extraction and culture of @entity1 skin keratinocytes and fibroblasts from very small cutaneous biopsies. In addition, a description of the protocols for the production of fibrotic dermal sheets can be found to obtain a model of fibrotic dermis that can be associated or not with a fully differentiated epidermis.

title: Reconstitution of skin XXXX development using a tissue engineering approach.

entities_list: @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis']

entities_list: @entity2631 :: ('MESH:D012594', 'Disease') :: ['scleroderma']

entities_list: @entity2805 :: ('MESH:D017439', 'Disease') :: ['hypertrophic scar']

answer: @entity82 :: (MESH:D005355,Disease) :: ['fibrosis']


abstract: 1. Potency and efficacy of @entity594 , @entity1855 and @entity3988 and of @entity9898 in modifying propulsion and nerve or smooth muscle activities have been compared in the @entity840 isolated distal colon. Both the neuronal and muscular effects of @entity141 channel blockers seem to develop at concentrations that are devoid of any significant effect apart from that on @entity141 channels. 2. @entity594 , @entity1855 and @entity3988 were all able to impair propulsion, resting and stimulated @entity934 ( @entity1617 ) release and smooth muscle contractility in a concentration-dependent way. However, some degree of selectivity for neuronal and muscular effects could be observed. @entity594 was more than 500 fold more potent than @entity1855 in relaxing musculature but less than twice as potent in reducing @entity1617 release. On the other hand, @entity1855 was the most efficacious @entity141 channel blocker tested in inhibiting @entity1617 release, its effects being inversely correlated to the external @entity141 concentration, and completely abolished by @entity9898 . 3. By comparing the potencies exhibited by each drug against peristaltic reflex, smooth muscle contractility and @entity1617 release, @entity1855 proved to be almost as potent in slowing the peristaltic reflex as in reducing @entity1617 release, while @entity594 was about 100 fold more potent against the peristaltic reflex than against @entity1617 release, but nearly equal against the peristaltic reflex and smooth muscle tone. Therefore, interference with cholinergic neurotransmission is likely to play a major role in the antipropulsive effect of @entity1855 , while peristaltic reflex impairment by @entity594 is likely to be dependent on inhibition of smooth muscle. 4. A facilitatory effect of @entity9898 on both the efficiency of the peristaltic reflex and the nonadrenergic, non-cholinergic (NANC) nerve-mediated relaxation could be observed at concentrations at least 10 fold lower than those required to affect @entity1617 release or smooth muscle. 5. It is concluded that the effects of @entity141 channel blockers on neurotransmitter release may be relevant to their effects on the gastrointestinal motor function.

title: Selectivity of XXXX channel blockers in inhibiting muscular and nerve activities in isolated colon.

entities_list: @entity1855 :: ('MESH:D014700', 'Chemical') :: ['verapamil']

entities_list: @entity3988 :: ('MESH:D004110', 'Chemical') :: ['diltiazem']

entities_list: @entity594 :: ('MESH:D009543', 'Chemical') :: ['nifedipine', 'Nifedipine']

entities_list: @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']

answer: @entity141 :: (CHEBI:29108,Chemical) :: ['Ca2+']


abstract: OBJECTIVE: The object of the study was to determine whether time of day, interval after a standard meal, and maternal body mass influence plasma @entity413 concentrations in @entity1 with @entity6 . STUDY DESIGN: Identical mixed meals were administered on 2 separate occasions 1 week apart to 30 @entity1 with dietarily treated gestational @entity6 and pregnancies between 28 and 38 weeks' gestation. One meal was administered at 7 AM (morning meal) and the other was administered at 9 PM (evening meal), each after a fast of >/=5 hours. The order of the meals (morning first versus evening first) was assigned randomly. Sixteen of the @entity1 had a body mass index >/=27 kg/m(2) (overweight) and 14 @entity1 had a body mass index <27 kg/m(2) (lean). Venous plasma concentrations of @entity413 , insulin, free @entity1718 , @entity4322 , and bound and free @entity701 were measured hourly for 9 hours after each of the test meals. RESULTS: When all @entity1 were considered together @entity413 concentrations after the morning meal were significantly greater at 1 hour, were not different at 2 hours, and were significantly lower from 3 through 9 hours postprandially than those at corresponding times after the evening meal. Plasma @entity4322 and free @entity844 concentrations were higher between 5 and 9 hours after the morning meal than at the same times after the evening meal. Total and free @entity701 levels were higher for the first 7 hours after the morning feeding, reflecting known diurnal variation in @entity701 concentrations. Overweight @entity1 ' @entity413 values were significantly greater than those of lean subjects during the last 4 hours of the overnight fast. CONCLUSIONS: Among @entity1 with dietarily treated gestational @entity6 the @entity413 concentrations were significantly higher from 3 to 9 hours after an evening meal, whereas suppression of free @entity1718 and @entity4322 was less sustained after a morning feeding. The mechanisms underlying these differences remain to be determined but may involve diurnal influences of counterregulatory hormones. The relationships between measurements of maternal glycemia and maternal and perinatal outcomes in pregnancies complicated by gestational @entity6 may be clarified by establishing a uniform duration of a fast and by developing meal-specific preprandial and postprandial maternal @entity413 targets for these @entity1 .

title: When is fasting really fasting? The influence of time of day, interval after a meal, and maternal body mass on maternal glycemia in gestational XXXX .

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

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

entities_list: @entity6 :: ('MESH:D003920', 'Disease') :: ['gestational diabetes mellitus', 'diabetes']

entities_list: @entity4322 :: ('MESH:D020155', 'Chemical') :: ['beta-hydroxybutyrate']

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

entities_list: @entity1718 :: ('MESH:D005227', 'Chemical') :: ['fatty acids']

entities_list: @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']

answer: @entity6 :: (MESH:D003920,Disease) :: ['diabetes']


abstract: OBJECTIVES: The objective was to test the efficacy and safety of 2 mg of intravenous (IV) @entity10748 ( @entity10748 ) against "usual care" in @entity341 ( @entity341 ) @entity1 with acute severe @entity158 . METHODS: This was a randomized clinical trial. @entity1 allocated to 2 mg of IV @entity10748 received their medication in a single dose. Those randomized to usual care received any IV opioid, with type, dose, and frequency chosen by the @entity341 attending. All @entity1 received 2 L/min. nasal cannula @entity26 . The primary outcome was the difference in the proportion of @entity1 who achieved clinically satisfactory @entity1337 by 30 minutes. This was defined as the @entity1 declining additional @entity1337 when asked the question, "Do you want more @entity158 medicine?" A 10% absolute difference was chosen a priori as the minimum difference considered clinically significant. RESULTS: Of 175 subjects randomized to each group, 164 in the 2 mg @entity10748 group and 161 in the usual care group had sufficient data for analysis. Additional @entity158 medication was declined by 77.4% of @entity1 in the 2 mg @entity10748 group at 30 minutes, compared to 65.8% in the usual care group. This difference of 11.6% was statistically and clinically significant (95% confidence interval [CI] = 1.8% to 21.1%). Safety profiles were similar and no @entity1 required @entity1510 . There was more @entity111 in the @entity10748 group (18.3% vs. 8.7%; difference = 9.6%, 95% CI = 2.6% to 16.6%). CONCLUSIONS: Using a simple dichotomous @entity1 -centered endpoint in which a difference of 10% in proportion obtaining adequate @entity1337 was considered clinically significant, 2 mg of @entity10748 in a single IV dose is clinically and statistically more efficacious when compared to usual care for acute @entity158 management in the @entity341 .

title: Randomized clinical trial of efficacy and safety of a single 2-mg intravenous dose of XXXX versus usual care in the management of acute @entity158 .

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

entities_list: @entity341 :: ('MESH:D004630', 'Disease') :: ['emergency department', 'ED']

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

entities_list: @entity1337 :: ('MESH:D000699', 'Disease') :: ['analgesia']

entities_list: @entity1510 :: ('MESH:D009270', 'Chemical') :: ['naloxone']

entities_list: @entity111 :: ('MESH:D011537', 'Disease') :: ['pruritus']

entities_list: @entity10748 :: ('MESH:D004091', 'Chemical') :: ['hydromorphone', 'Dilaudid']

answer: @entity10748 :: (MESH:D004091,Chemical) :: ['hydromorphone']


abstract: BACKGROUND: Preclinical and clinical data suggest synergy for @entity136 and @entity901 . These agents were tested in several known @entity5 that also comprise the common @entity189 ( @entity189 ) subtypes; namely, lung and pancreaticobiliary profiles. METHODS: The study enrolled 29 @entity1 of whom 28 @entity1 were eligible for treatment. @entity136 was given at 1,000 mg/m(2) as a fixed dose rate infusion and @entity901 was infused at 100 mg/m(2) every 2 weeks with restaging performed after 3 cycles at 6 weeks. RESULTS: The study reported one complete response (CR) (4%), 6 @entity1 with a partial response (PR) (25%), and 13 with @entity66 ( @entity66 ) (54%); and 4 @entity1 had @entity74 ( @entity74 ) (17%) on restaging. Median overall survival (OS) and progression-free survival were 12.8 months (95% confidence interval [CI] 8.5-18.5) and 3.1 months (95% CI 1.7-6), respectively. The 1-year OS was 54%. The most common grade 3 @entity137 were @entity390 (22%), @entity391 (15%), and @entity1295 (11%). There were no grade 4 @entity137 . This study was closed early as we moved from an empiric therapy platform to a more individualized approach. CONCLUSIONS: @entity136 and @entity901 is a well-tolerated regimen in @entity189 with similar outcomes to previously documented @entity189 studies. In selected good performance status @entity1 this combination may serve as a first-line doublet chemotherapy option for @entity189 @entity1 .

title: A phase II study to evaluate the efficacy and @entity137 of XXXX in combination with @entity136 in @entity189 .

entities_list: @entity901 :: ('MESH:C030110', 'Chemical') :: ['oxaliplatin']

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

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

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

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

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

entities_list: @entity189 :: ('MESH:D002277', 'Disease') :: ['CUP', 'carcinoma of unknown primary']

entities_list: @entity74 :: ('MESH:D030342', 'Disease') :: ['PD', 'progressive disease']

entities_list: @entity136 :: ('MESH:C056507', 'Chemical') :: ['Gemcitabine', 'gemcitabine']

answer: @entity901 :: (MESH:C030110,Chemical) :: ['oxaliplatin']


abstract: In flowering plants, two cells are fertilized in the haploid female gametophyte. Egg and sperm nuclei fuse to form the embryo. A second sperm nucleus fuses with the central cell nucleus that replicates to generate the endosperm, which is a tissue that supports embryo development. MEDEA ( @entity41336 ) encodes an @entity958 SET domain Polycomb protein. Inheritance of a maternal loss-of-function @entity41336 allele results in embryo abortion and prolonged endosperm production, irrespective of the genotype of the paternal allele. Thus, only the maternal wild-type @entity41336 allele is required for proper embryo and endosperm development. To understand the molecular mechanism responsible for the parent-of-origin effects of @entity41336 mutations on seed development, we compared the expression of maternal and paternal @entity41336 alleles in the progeny of crosses between two @entity958 ecotypes. Only the maternal @entity41336 mRNA was detected in the endosperm from seeds at the torpedo stage and later. By contrast, expression of both maternal and paternal @entity41336 alleles was observed in the embryo from seeds at the torpedo stage and later, in seedling, leaf, stem, and root. Thus, @entity41336 is an imprinted gene that displays parent-of-origin-dependent monoallelic expression specifically in the endosperm. These results suggest that the embryo abortion observed in mutant @entity41336 seeds is due, at least in part, to a defect in endosperm function. Silencing of the paternal @entity41336 allele in the endosperm and the phenotype of mutant @entity41336 seeds supports the parental conflict theory for the evolution of imprinting in plants and mammals.

title: Imprinting of the MEDEA polycomb gene in the XXXX endosperm.

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

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


abstract: BACKGROUND: The @entity5 is an important watchpoint in the follow-up observation of the @entity1 . However, potential @entity5 of @entity8407 cannot be estimated by histopathologic assessment alone. We evaluated @entity74 at the level of copy number variation ( @entity471 ) to investigate the risk for developing @entity5 in @entity8407 . MATERIALS AND METHODS: The current study used 27 @entity8407 with histological evidence of @entity1141 . The first group (progressing @entity1141 ) consisted of 7 oral lesions from @entity1 with later progression to @entity5 at the same site. The other group (non- progressing @entity1141 ) consisted of 20 lesions from @entity1 with no occurrence of @entity5 and longitudinal follow up (>7 years). We extracted DNA from Formalin-Fixed Paraffin-Embedded (FFPE) samples and examined chromosomal loci and frequencies of CNVs using Taqman copy number assays. RESULTS: @entity471 frequently occurred at 3p, 9p, and 13q loci in progressing @entity1141 . Our results also indicate that @entity471 at multiple loci-in contrast to single locus occurrences-is characteristic of progressing @entity1141 . CONCLUSIONS: This study suggests that @entity74 of the true precancer demonstrate the progression risk which cannot be delineated by current histopathologic diagnosis.

title: XXXX in @entity8407 and @entity5 .

entities_list: @entity8407 :: ('MESH:D007972', 'Disease') :: ['oral leukoplakia', 'oral leukoplakias']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer progression of oral leukoplakia', 'cancer', 'oral cancer', 'malignancies']

entities_list: @entity74 :: ('MESH:D030342', 'Disease') :: ['genetic abnormalities']

entities_list: @entity1141 :: ('MESH:C535662', 'Disease') :: ['dysplasia']

answer: @entity74 :: (MESH:D030342,Disease) :: ['Genetic Abnormalities']


abstract: In the course of immunoscreening of @entity2440 cDNA library, a cDNA CsRP12 containing a tandem repeat was isolated. The cDNA CsRP12 encodes two putative peptides of open reading frames (ORFs) 1 and 2 (CsRP12-1 and -2). The repetitive region is composed of 15 repeats of 10 @entity1522 . Of the two putative peptides, CsRP12-1 was @entity1521 -rich and found to have homologues in several organisms. Recombinant proteins of the putative peptides were bacterially produced and purified by an affinity chromatography. Recombinant CsRP12-1 protein was recognized by sera of @entity14007 @entity1 and experimental @entity95 , but recombinant CsRP12-2 was not. One of the putative peptide, CsRP12-1, is designated CsPRA, @entity1521 -rich antigen of @entity2441 . Both the C-termini of CsRP12-1 and -2 were bacterially produced and analysed to show no antigenicity. Recombinant CsPRA protein showed high sensitivity and specificity. In experimental rabbits, IgG antibodies to CsPRA was produced between 4 and 8 weeks after the infection and decreased thereafter over one year. These results indicate that CsPRA is equivalent to a natural protein and a useful antigenic protein for serodiagnosis of @entity1 @entity14007 .

title: Molecular cloning and characterization of an antigenic protein with a repeating region from XXXX .

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

entities_list: @entity1522 :: ('CHEBI:33709', 'Chemical') :: ['amino acids']

entities_list: @entity14007 :: ('MESH:D003003', 'Disease') :: ['clonorchiasis']

entities_list: @entity2440 :: ('79923', 'Species') :: ['Clonorchis sinensis']

entities_list: @entity1521 :: ('CHEBI:26271', 'Chemical') :: ['proline']

answer: @entity2440 :: (79923,Species) :: ['Clonorchis sinensis']


abstract: In order to examine the prevalence of @entity1374 in a hospital outpatient setting, in an area of sufficient @entity1496 intake, serum levels of TSH, T4, T3, anti-Tg and anti- @entity5787 antibodies were examined in 909 individuals with an age range of 12.4 to 88.5 years, participating in a checkup outpatient setting. The study was conducted in Henry Dynant Hospital located in the metropolitan area of Athens, Greece, during a 2 year period. Hormonal parameters were determined by chemiluminescence immunoassay. Overt @entity2743 was found in 4.95% of the total population and subclinical @entity2743 in 5.5%. Overt @entity1375 was found in 1.43% and @entity1375 in 4.51%. In male population, overt @entity2743 was found in 4.4 % and subclinical @entity2743 was also found in 4.4%. On the other hand, overt @entity1375 was found in 1.4% and @entity1375 was found in 3.7% in males. In female population, overt @entity2743 was found in 5.2% whereas subclinical @entity2743 was found in 6.0%. Overt @entity1375 was found in 1.5% and @entity1375 was found in 4,9% in females. Positive anti- @entity5787 antibodies were detected more often (30.4%) than anti-Tg (15.4%) in the tested population. The positivity in both anti- @entity5787 and anti-Tg antibodies was correlated with abnormally high @entity10344 concentrations after the age of 50 years, especially in female population. In conclusion distinct profile of thyroid hormonal parameters was observed in inhabitants in the metropolitan area of Athens, with overt @entity2743 strikingly overcome overt @entity1375 while subclinical forms of each dysfunction also exhibit analogous results.

title: Thyroid function and prevalence of anti- @entity5787 ( XXXX ) and anti-thyroglobulin (Tg) antibodies in outpatients hospital setting in an area with sufficient @entity1496 intake: influences of age and sex.

entities_list: @entity1375 :: ('MESH:D007037', 'Disease') :: ['subclinical hypothyroidism', 'hypothyroidism']

entities_list: @entity2743 :: ('MESH:D006111', 'Disease') :: ['thyrotoxicosis']

entities_list: @entity1374 :: ('MESH:D013959', 'Disease') :: ['thyroid disease']

answer: @entity5787 :: (7173,Gene) :: ['TPO']


abstract: The purpose of this investigation was to assess the influence of @entity4388 supplementation on maximal force production, rate of force development (RFD), and muscle recruitment during repeated bouts of high-intensity cycling. Ten male and female (n = 10) subjects completed two fixed-cadence, high-intensity cycling trials. Each trial consisted of a series of 30-s efforts at 120% peak power output (maximum graded test) that were interspersed with 30-s recovery periods until task failure. Prior to each trial, subjects consumed 0.3 g/kg @entity4388 ( @entity7041 ) or placebo ( @entity1989 ). @entity2472 were performed immediately after each 30-s effort. Maximal force (F max) was calculated as the greatest force recorded over a 25-ms period throughout the entire contraction duration while maximal RFD (RFD max) was calculated as the greatest 10-ms average slope throughout that same contraction. F max declined similarly in both the @entity7041 and @entity1989 conditions, with baseline values ( @entity7041 : 1,226    393 N; @entity1989 : 1,222    369 N) declining nearly 295    54 N [95% confidence interval (CI) = 84-508 N; P < 0.006]. RFD max also declined in both trials; however, a differential effect persisted between the @entity7041 and @entity1989 conditions. A main effect of condition was observed across the performance time period, with RFD max on average higher during @entity7041 ( @entity7041 : 8,729    1,169 N/s; @entity1989 : 7,691    1,526 N/s; mean difference between conditions 1,038    451 N/s, 95% CI = 17-2,059 N/s; P < 0.048). These results demonstrate a differential effect of @entity5838 on maximum force vs. maximum rate of force development during a whole body fatiguing task.

title: The differential effect of XXXX on maximum force and rate of force development during repeated, high-intensity cycling.

entities_list: @entity4388 :: ('MESH:D017693', 'Chemical') :: ['sodium bicarbonate']

entities_list: @entity5838 :: ('MESH:D000471', 'Disease') :: ['alkalosis']

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

answer: @entity5838 :: (MESH:D000471,Disease) :: ['metabolic alkalosis']


abstract: Mitogen-activated protein kinases (MAPKs) are @entity563 / @entity1889 kinases that are rapidly activated in response to a variety of growth factors in many cell types. MAPKs are activated by phosphorylation of both @entity669 and @entity1889 residues. They are proposed to be key integrators of growth factor receptor transduction systems involving conversion of @entity669 kinase signals to @entity563 / @entity1889 kinase activation. We have studied the influence of specific oncogenes on the regulation of MAPK activity in NIH 3T3 and @entity35 1a fibroblasts. In NIH 3T3 cells, ras or @entity19705 oncogene expression, but not gip2 oncogene expression, induces a significant constitutive MAPK activation. In contrast, in @entity35 1a cells, gip2, but not ras or @entity19705 oncogene expression, induces a strong constitutive MAPK activation. The findings indicate that, in a cell type-selective manner, different oncoproteins are capable of causing the constitutive activation of MAPK. However, the magnitude of oncogene-induced MAPK activation is not directly correlated with cellular transformation in either cell type. It appears that expression of only a subset of transforming oncogenes in a specific cell type is able to alter the regulation of the MAPK activation pathway. Thus, the network of cytoplasmic @entity563 / @entity1889 kinases will be differentially regulated when the same oncogene is expressed in different cell types.

title: Mitogen-activated protein kinase activation resulting from selective oncogene expression in NIH 3T3 and XXXX 1a cells.

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

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

entities_list: @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine']

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


abstract: Six @entity1 died of @entity791 ( @entity791 ), four of them females, ages 7 months, 13 months, 2 years 8 months, and 4 years; and two of them males, aged 2 1/2 and 7 years. They were born to IV @entity734 parents. The conduction system (CS) and the entire heart were studied by serial section. In all cases the heart was @entity1184 and enlarged; one had total @entity715 of the right coronary artery with extensive @entity1188 of the ventricular septum. Vascular changes also were found in all hearts, involving small arteries, arterioles, and venules. In the arteries, they involved the intima, media, and adventitia, and perivascular areas in a degenerative and inflammatory process. The elastic tissue was especially affected. A nonspecific @entity2401 was present in four cases and epicarditis in all. Changes in the summit of the ventricular septum were present in four cases, consisting of increased @entity82 and @entity8994 . The CS changes varied in location, showing either @entity1333 , @entity2401 , or fragmentation of the bundle with lobulation and @entity82 . The changes in the conduction system were not as severe as the changes in the surrounding myocardium. In one case the ECG was abnormal, showing @entity1002 . This corresponded to the finding of @entity82 , vacuolization of cells, and space formation in the left bundle branch.

title: Conduction system in @entity1 with XXXX .

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

entities_list: @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis']

entities_list: @entity8994 :: ('MESH:D050379', 'Disease') :: ['arteriolosclerosis']

entities_list: @entity1333 :: ('MESH:D014657', 'Disease') :: ['vasculitis']

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

entities_list: @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarction']

entities_list: @entity2401 :: ('MESH:D009205', 'Disease') :: ['myocarditis']

entities_list: @entity715 :: ('MESH:D013927', 'Disease') :: ['thrombotic occlusion']

entities_list: @entity791 :: ('MESH:D000163', 'Disease') :: ['acquired immunodeficiency syndrome', 'AIDS']

entities_list: @entity734 :: ('MESH:D019966', 'Disease') :: ['drug-addicted']

entities_list: @entity1002 :: ('MESH:D018487', 'Disease') :: ['left hemiblock']

answer: @entity791 :: (MESH:D000163,Disease) :: ['acquired immunodeficiency syndrome']


abstract: BACKGROUND AND OBJECTIVE: The endovascular treatment of @entity1028 has raised great interest amongst vascular surgeons. The aim of this study was to compare the postoperative morbidity and mortality rates of endovascular treatment with those of open surgery, from the anaesthesiologist's standpoint. METHODS: From January 1997 to June 2000, 425 consecutive @entity1 with @entity1028 were referred for regular surgery. Thirty-nine @entity1 who needed a visceral or renal artery revascularization, or a nephrectomy were excluded. The remaining 386 @entity1 were studied in a prospective manner. @entity439 were evaluated with spiral computerized tomography scanning and calibrated aortography. After informed consent, only those @entity1 with a suitable vascular anatomy underwent endovascular treatment (n = 193). All other @entity1 underwent open surgery and are considered as a control group (n = 193). Endovascular treatment was performed by a femoral or an iliac retroperitoneal route. All stent-grafts were made to measure using auto-expandable stainless-steel stents covered with a standard polyester prosthetic graft. RESULTS: Six @entity1 in the endovascular treatment group needed to be converted to the open surgical technique (during the same operation) because of @entity397 of the iliac bifurcation (1 @entity1 ), a large endoleak (2 @entity1 ), or technical problems (3 @entity1 ). CONCLUSION: The amount of @entity548 and the need for blood products were significantly lower in the endovascular treatment group. Despite the absence of significant differences regarding cardiac complications and mortality, there was a lesser incidence of @entity55 , acute respiratory and @entity177 . @entity1 in the endovascular treatment group spent less time in the intensive care unit and in the Hospital.

title: Endovascular treatment of XXXX : is there a benefit regarding postoperative outcome?

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

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

entities_list: @entity55 :: ('MESH:D011014', 'Disease') :: ['pneumonia']

entities_list: @entity177 :: ('MESH:D051437', 'Disease') :: ['renal failure']

entities_list: @entity439 :: ('MESH:D000783', 'Disease') :: ['Aneurysms']

entities_list: @entity1028 :: ('MESH:D017544', 'Disease') :: ['abdominal aortic aneurysms']

answer: @entity1028 :: (MESH:D017544,Disease) :: ['abdominal aortic aneurysms']


abstract: Altogether 38 postpubertal @entity1 with @entity66 were rebiopsied. @entity10900 in nine (24%) of them indicated poor adherence to the diet. Gluten challenge with a diet containing a normal amount of gluten was performed in those 29 @entity1 with a normal mucosa. During challenge, rebiopsy was done when @entity34576 antibodies turned positive (mean 0.6 years, range 0.2-2.0) or at the end of the two year study. Histologically a clear relapse into @entity66 was seen in all 23 @entity1 who were positive for reticulin antibodies. At this time gliadin antibodies were positive in all but two. Sixteen (70%) of those who relapsed were completely asymptomatic. Three @entity1 and one @entity1 did not relapse within two years, indicating the possible recovery from @entity66 to be 11%. All four had undergone gluten challenge earlier in childhood, after initial diagnosis and mucosal recovery, and this had resulted in mucosal relapse. To establish definite postpubertal recovery from @entity66 in cases with normal mucosa at two years from challenge, further follow up studies of reticulin antibodies and later rebiopsy are needed. The reticulin antibody test seems to be suitable for prediction of mucosal relapse in @entity66 .

title: Postpubertal gluten challenge in XXXX .

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

entities_list: @entity34576 :: ('CHEBI:24750', 'Chemical') :: ['reticulin']

entities_list: @entity10900 :: ('MESH:D009056', 'Disease') :: ['Mucosal abnormality']

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

answer: @entity66 :: (MESH:D004194,Disease) :: ['coeliac disease']


abstract: This study has been conducted on 17 @entity1 suffering from @entity308 , who had not received a pharmacological antidepressive therapy since at least 1 month. 6 @entity1 suffering from @entity308 were treated with 100 mg @entity8991 i.v. daily for 20 days; 11 @entity1 , 7 of whom suffered from @entity308 and 4 from @entity308 , were treated with 150 mg @entity5081 i.v. daily for 20 days. In both groups the therapy has been continued orally. In 17 @entity1 a remarkable improvement and even in some cases complete recovery has been obtained. The two psychotropic antidepressive drugs are, furthermore, both active in the same symptoms. The determination of @entity750 in @entity1 platelets confirms the strong inhibition of its re-uptake by @entity8991 and the absence of re-uptake of @entity750 with @entity5081 . A constant and progressive increase of @entity5581 was noted in @entity1 treated with @entity8991 . This increase may be considered as a consequence of the increased metabolism of the larger quantitity of @entity750 used by the central synapses. The interpretation of the increased levels of @entity5581 in @entity1 treated with @entity5081 is more difficult. Further trials, for instance on the plasmatic @entity2340 level, will perhaps solve the problem.

title: [Clinical and biochemical contributions on the effect of @entity5081 and @entity8991 in XXXX states (preliminary observation)].

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

entities_list: @entity308 :: ('MESH:D003866', 'Disease') :: ['neurotic and psychotic depressions', 'neurotic depression', 'psychotic depression']

entities_list: @entity8991 :: ('MESH:D002997', 'Chemical') :: ['clomipramine']

entities_list: @entity5081 :: ('MESH:D008376', 'Chemical') :: ['maprotiline']

entities_list: @entity2340 :: ('CHEBI:27897', 'Chemical') :: ['tryptophan']

answer: @entity308 :: (MESH:D003866,Disease) :: ['depressive']


abstract: Arthroscopically guided reconstruction of the anterior cruciate ligament is a common orthopaedic procedure. While many associated complications have been described in the literature, @entity5414 has received little attention. Although rare after anterior cruciate ligament reconstruction, @entity5414 can have devastating consequences. From a group of 831 consecutive @entity1 , we report 4 (0.48%) who sustained @entity5414 . All @entity1 had similar symptoms and were treated by the same surgeon in the same manner. All underwent immediate arthroscopic lavage, open incision, drainage of associated wounds, debridement with graft retention, and treatment with intravenous and then oral antibiotics. The @entity1 underwent an average of 2.75 procedures after the diagnosis to eradicate the @entity281 and restore knee motion. All @entity1 were evaluated at an average of 3 years after surgery. We found that previous knee surgery and meniscal repair were risk factors for the development of @entity5414 . The @entity281 was successfully eradicated, the ligament graft was preserved, and knee stability and mobility were adequately restored in all @entity1 . However, the clinical outcome of these @entity1 appeared to be inferior to that of @entity1 who had undergone uncomplicated anterior cruciate ligament reconstruction. This inferior outcome appeared to be secondary to damage to the articular cartilage from the @entity281 .

title: Outcomes of XXXX after anterior cruciate ligament reconstruction.

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

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

entities_list: @entity5414 :: ('MESH:D001170', 'Disease') :: ['septic arthritis', 'postoperative septic arthritis']

answer: @entity5414 :: (MESH:D001170,Disease) :: ['postoperative septic arthritis']