abstract: Activation of T lymphocytes is initiated by receptor ligand interactions at the cell surface leading to the transduction of intracellular signals followed by the de novo synthesis and expression of T cell activation markers (including receptors for @entity1199 ( @entity1199 ) and @entity69 ), production of @entity7508 , and T cell proliferation. This requisite first step for activation of T lymphocytes can be mimicked in certain situations with a variety of stimuli. These include antibodies to certain integral membrane proteins, @entity4996 , and plant lectins that act as mitogens. In this paper, we report that at least two classes of @entity1 T cell clones can be distinguished based upon signal requirements necessary to induce proliferation. Although all clones analyzed expressed @entity1199 receptors and secreted @entity1199 after non-antigenic activation, one subset of clones did not proliferate in response to the same non-antigenic signals. In that subset, complete activation leading to proliferation required interaction of the T cell with specific antigen. The ability to subset these T cell clones into two groups did not correlate with phenotypic differences, source of the clone, nor with magnitude of intracellular @entity460 mobilization. By studying the stimulation requirements of these two subsets of @entity1 T cell clones through the use of specific antigen or antigen-independent stimuli, it was possible to demonstrate that different stimuli varied in their ability to induce steps of T cell activation. Analysis of reactivity of these clones to suboptimal stimulation allowed the definition of intermediate stages of T cell activation. Such intermediate stages might reflect a diversity of intracellular signaling pathways or a complexity of regulatory mechanisms distal to the events that allow intracellular @entity460 mobilization. Thus for the first time, it has been possible to study ordered events of T cell activation in non-transformed, antigen-dependent @entity1 T lymphocytes. The data presented in this paper suggest that T cell activation is not an all or nothing phenomenon, and there is an ordered sequence of events that can be differentiated based upon signal requirements at the T cell membrane.

title: Heterogeneity of signal requirements in T cell activation within a panel of XXXX proliferative T cell clones.

entities_list: @entity7508 :: ('MESH:D008222', 'Chemical') :: ['lymphokines']

entities_list: @entity4996 :: ('MESH:D010703', 'Chemical') :: ['phorbol esters']

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


abstract: BACKGROUND: Cryptococcal @entity39 that is localized to the lower extremities is very rare. OBJECTIVE: We describe a case of a renal transplant recipient who presented with @entity39 caused by @entity11937 fungus that is rarely associated with this disease. METHODS: This is a case report with literature review. RESULTS: The @entity1 was hospitalized, and the site of infection was debrided to the level of the periosteum. Cultures and histopathologic examination of biopsy material revealed an invasive @entity281 with a fungal organism that was consistent with @entity1327 . After 21 days on parenteral @entity2379 (Ambisome; Er-Kim Pharmaceuticals) treatment, the @entity1 was switched to oral @entity2059 (Itraspor; Janssen-Cilag Pharmaceuticals) 200 mg/day. He was discharged after 30 days of hospitalization with his wounds completely healed. He continued on oral @entity2380 for a total course of 6 weeks. CONCLUSION: Systemic @entity364 continue to be an important cause of morbidity and mortality in transplant recipients. The insidious nature and atypical manifestations of these infections often delay diagnosis and therapy. In immunosuppressed @entity1 , persistent @entity221 that does not respond to antibacterial therapy should alert the physician to the possibility of @entity364 .

title: Cryptococcal XXXX with multiple sites of involvement in the lower extremities.

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

entities_list: @entity2379 :: ('MESH:D000666', 'Chemical') :: ['amphotericin B']

entities_list: @entity39 :: ('MESH:D009336', 'Disease') :: ['necrotizing fasciitis', 'necrotizing fasciitis of the legs']

entities_list: @entity2380 :: ('MESH:D015725', 'Chemical') :: ['fluconazole']

entities_list: @entity11937 :: ('178876', 'Species') :: ['Cryptococcus neoformans, a']

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

entities_list: @entity364 :: ('MESH:D009181', 'Disease') :: ['fungal infections', 'fungal infection']

entities_list: @entity2059 :: ('MESH:D017964', 'Chemical') :: ['itraconazole']

answer: @entity39 :: (MESH:D009336,Disease) :: ['necrotizing fasciitis']


abstract: The relationship between @entity409 and @entity73 in @entity1 with @entity1294 ( @entity1294 ) and @entity195 ( @entity195 ) with @entity66 ( @entity66 ) suggests a potential role for cholinomimetic therapy. Initial studies of @entity11545 demonstrated cognitive, behavioral, and functional benefits in these populations. 326 @entity1 with @entity1294 or @entity195 with @entity66 who completed an initial 12-month trial were treated with @entity11545 24 mg/day in a 24-month, open-label extension. This interim analysis was performed at month 12 of the open-label extension (248 completed the trial). @entity11545 (up to 24 months total) was well tolerated in both groups. The most frequently reported adverse events, characteristic of older @entity303 @entity1 , included @entity308 , @entity2146 , and @entity22 . Gastrointestinal adverse events were less common than initially, indicating declining incidence with long-term therapy. @entity1 taking @entity11545 for the entire study demonstrated the least @entity73 on @entity195 Assessment Scale-cog/11: 2.7 points vs. 3.1 points in those given placebo initially (P < 0.001 and P = 0.003, respectively). The long-term benefits of @entity11545 were evident in both groups; cognitive baseline levels were maintained for approximately 21 months in @entity1294 @entity1 and for 12 months in @entity1 with @entity195 with @entity66 . Long-term (up to 24 months) @entity11545 therapy in @entity1 with @entity1294 and @entity195 with @entity66 is well tolerated and associated with prolonged maintenance of cognitive function.

title: Long-term safety and cognitive effects of @entity11545 in the treatment of probable @entity1294 or @entity195 with XXXX .

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

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

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

entities_list: @entity303 :: ('MESH:D003704', 'Disease') :: ['dementia']

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

entities_list: @entity1294 :: ('MESH:D015140', 'Disease') :: ['vascular dementia', 'VaD']

entities_list: @entity409 :: ('MESH:D008107', 'Disease') :: ['cholinergic dysfunction']

entities_list: @entity11545 :: ('MESH:D005702', 'Chemical') :: ['galantamine', 'Galantamine']

entities_list: @entity2146 :: ('MESH:D011595', 'Disease') :: ['agitation']

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

entities_list: @entity22 :: ('MESH:D007319', 'Disease') :: ['insomnia']

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


abstract: The relationship between @entity409 and @entity73 in @entity1 with @entity1294 ( @entity1294 ) and @entity195 ( @entity195 ) with @entity66 ( @entity66 ) suggests a potential role for cholinomimetic therapy. Initial studies of @entity11545 demonstrated cognitive, behavioral, and functional benefits in these populations. 326 @entity1 with @entity1294 or @entity195 with @entity66 who completed an initial 12-month trial were treated with @entity11545 24 mg/day in a 24-month, open-label extension. This interim analysis was performed at month 12 of the open-label extension (248 completed the trial). @entity11545 (up to 24 months total) was well tolerated in both groups. The most frequently reported adverse events, characteristic of older @entity303 @entity1 , included @entity308 , @entity2146 , and @entity22 . Gastrointestinal adverse events were less common than initially, indicating declining incidence with long-term therapy. @entity1 taking @entity11545 for the entire study demonstrated the least @entity73 on @entity195 Assessment Scale-cog/11: 2.7 points vs. 3.1 points in those given placebo initially (P < 0.001 and P = 0.003, respectively). The long-term benefits of @entity11545 were evident in both groups; cognitive baseline levels were maintained for approximately 21 months in @entity1294 @entity1 and for 12 months in @entity1 with @entity195 with @entity66 . Long-term (up to 24 months) @entity11545 therapy in @entity1 with @entity1294 and @entity195 with @entity66 is well tolerated and associated with prolonged maintenance of cognitive function.

title: Long-term safety and cognitive effects of XXXX in the treatment of probable @entity1294 or @entity195 with @entity66 .

answer: @entity11545 :: (MESH:D005702,Chemical) :: ['galantamine']


abstract: The relationship between @entity409 and @entity73 in @entity1 with @entity1294 ( @entity1294 ) and @entity195 ( @entity195 ) with @entity66 ( @entity66 ) suggests a potential role for cholinomimetic therapy. Initial studies of @entity11545 demonstrated cognitive, behavioral, and functional benefits in these populations. 326 @entity1 with @entity1294 or @entity195 with @entity66 who completed an initial 12-month trial were treated with @entity11545 24 mg/day in a 24-month, open-label extension. This interim analysis was performed at month 12 of the open-label extension (248 completed the trial). @entity11545 (up to 24 months total) was well tolerated in both groups. The most frequently reported adverse events, characteristic of older @entity303 @entity1 , included @entity308 , @entity2146 , and @entity22 . Gastrointestinal adverse events were less common than initially, indicating declining incidence with long-term therapy. @entity1 taking @entity11545 for the entire study demonstrated the least @entity73 on @entity195 Assessment Scale-cog/11: 2.7 points vs. 3.1 points in those given placebo initially (P < 0.001 and P = 0.003, respectively). The long-term benefits of @entity11545 were evident in both groups; cognitive baseline levels were maintained for approximately 21 months in @entity1294 @entity1 and for 12 months in @entity1 with @entity195 with @entity66 . Long-term (up to 24 months) @entity11545 therapy in @entity1 with @entity1294 and @entity195 with @entity66 is well tolerated and associated with prolonged maintenance of cognitive function.

title: Long-term safety and cognitive effects of @entity11545 in the treatment of probable @entity1294 or XXXX with @entity66 .

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


abstract: The relationship between @entity409 and @entity73 in @entity1 with @entity1294 ( @entity1294 ) and @entity195 ( @entity195 ) with @entity66 ( @entity66 ) suggests a potential role for cholinomimetic therapy. Initial studies of @entity11545 demonstrated cognitive, behavioral, and functional benefits in these populations. 326 @entity1 with @entity1294 or @entity195 with @entity66 who completed an initial 12-month trial were treated with @entity11545 24 mg/day in a 24-month, open-label extension. This interim analysis was performed at month 12 of the open-label extension (248 completed the trial). @entity11545 (up to 24 months total) was well tolerated in both groups. The most frequently reported adverse events, characteristic of older @entity303 @entity1 , included @entity308 , @entity2146 , and @entity22 . Gastrointestinal adverse events were less common than initially, indicating declining incidence with long-term therapy. @entity1 taking @entity11545 for the entire study demonstrated the least @entity73 on @entity195 Assessment Scale-cog/11: 2.7 points vs. 3.1 points in those given placebo initially (P < 0.001 and P = 0.003, respectively). The long-term benefits of @entity11545 were evident in both groups; cognitive baseline levels were maintained for approximately 21 months in @entity1294 @entity1 and for 12 months in @entity1 with @entity195 with @entity66 . Long-term (up to 24 months) @entity11545 therapy in @entity1 with @entity1294 and @entity195 with @entity66 is well tolerated and associated with prolonged maintenance of cognitive function.

title: Long-term safety and cognitive effects of @entity11545 in the treatment of probable XXXX or @entity195 with @entity66 .

answer: @entity1294 :: (MESH:D015140,Disease) :: ['vascular dementia']


abstract: AIM: To find an objective method of adjusting sling @entity2701 in order to avoid postoperative @entity1876 . METHODS: Thirty-five female @entity1 with @entity3142 were treated using a sling procedure. @entity4438 were implanted in 20 @entity1 and @entity736 patch slings with nylon sutures were implanted in 15 @entity1 . During the procedures the urinary bladder was partially full and the @entity1 , who were under spinal or epidural anesthesia, were asked to cough and strain. The proper @entity2701 that effectively prevents urine leakage was selected and the corresponding suture length was marked. An objective new method to adjust sling @entity2701 was used. As part of this method, the abdominal bulge index is added to the suture length before tying. RESULTS: Short-term follow-up of 6-12 months showed that 33 of 35 @entity1 reported no @entity2680 (94%). Two @entity1 had unsatisfactory urge incontinence. We did not encounter postoperative urinary retention in any @entity1 . No significant post-voiding residual urine was reported. None of our @entity1 in this series have complained of difficulties during micturition or the need to strain during voiding. CONCLUSION: Proper adjustment of sling @entity2701 using the abdominal bulge index has eliminated postoperative urinary retention and obstructed urine flow, including any appreciable amount of post-voiding residual urine. This method has been found to be both objective and reproducible.

title: Sling operations in the treatment of stress urinary incontinence: how to adjust sling XXXX .

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

entities_list: @entity4438 :: ('MESH:C563219', 'Disease') :: ['Pubovaginal fascial slings']

entities_list: @entity2680 :: ('MESH:D003763', 'Disease') :: ['leakage of urine']

entities_list: @entity736 :: ('CHEBI:53251', 'Chemical') :: ['polytetrafluoroethylene']

entities_list: @entity1876 :: ('MESH:D001748', 'Disease') :: ['urinary obstruction']

entities_list: @entity3142 :: ('MESH:D014550', 'Disease') :: ['type II/III and type III stress urinary incontinence']

answer: @entity2701 :: (MESH:D018781,Disease) :: ['tension']


abstract: Risk assessments include assumptions about sensitive subpopulations, such as the fraction of the general population that is sensitive and the extent that biochemical or physiological attributes influence sensitivity. Uncertainty factors (UF) account for both pharmacokinetic (PK) and pharmacodynamic (PD) components, allowing the inclusion of risk-relevant information to replace default assumptions about PK and PD variance (uncertainty). Large numbers of @entity1 organ donor samples and recent advances in methods to extrapolate in vitro enzyme expression and activity data to the intact @entity1 enable the investigation of the impact of PK variability on @entity1 susceptibility. The hepatotoxicity of @entity4965 ( @entity4966 ) is mediated by acid metabolites formed by @entity5321 ( @entity5321 ) oxidation, and differences in the @entity5321 expression are hypothesized to affect susceptibility to @entity4966 's @entity99 . This study was designed specifically to examine the contribution of statistically quantified variance in enzyme content and activity on the risk of @entity130 among adult @entity1 . We combined data sets describing (1) the microsomal protein content of @entity1 liver, (2) the @entity5321 content of @entity1 liver microsomal protein, and (3) the in vitro Vmax for @entity4966 oxidation by @entity1 . The 5th and 95th percentiles of the resulting distribution ( @entity4966 oxidized per minute per gram liver) differed by approximately sixfold. These values were converted to mg @entity4966 oxidized/h/kg body mass and incorporated in a @entity1 PBPK model. Simulations of 8-hour inhalation exposure to 50 ppm and oral exposure to 5 micro g @entity4966 /L in 2 L drinking water showed that the amount of @entity4966 oxidized in the liver differs by 2% or less under extreme values of @entity5321 expression and activity (here, selected as the 5th and 95th percentiles of the resulting distribution). This indicates that differences in enzyme expression and @entity4966 oxidation among the central 90% of the adult @entity1 population account for approximately 2% of the difference in production of the risk-relevant PK outcome for @entity4966 -mediated @entity99 . Integration of in vitro metabolism information into physiological models may reduce the uncertainties associated with risk contributions of differences in enzyme expression and the UF that represent PK variability.

title: The impact of XXXX -dependent metabolic variance on a risk-relevant pharmacokinetic outcome in @entity1 .

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

entities_list: @entity99 :: ('MESH:D056486', 'Disease') :: ['liver injury']

entities_list: @entity4965 :: ('MESH:D014241', 'Chemical') :: ['trichloroethylene']

entities_list: @entity130 :: ('MESH:D014947', 'Disease') :: ['hepatotoxic injury']

answer: @entity5321 :: (1571,Gene) :: ['cytochrome P450 2E1']


abstract: Risk assessments include assumptions about sensitive subpopulations, such as the fraction of the general population that is sensitive and the extent that biochemical or physiological attributes influence sensitivity. Uncertainty factors (UF) account for both pharmacokinetic (PK) and pharmacodynamic (PD) components, allowing the inclusion of risk-relevant information to replace default assumptions about PK and PD variance (uncertainty). Large numbers of @entity1 organ donor samples and recent advances in methods to extrapolate in vitro enzyme expression and activity data to the intact @entity1 enable the investigation of the impact of PK variability on @entity1 susceptibility. The hepatotoxicity of @entity4965 ( @entity4966 ) is mediated by acid metabolites formed by @entity5321 ( @entity5321 ) oxidation, and differences in the @entity5321 expression are hypothesized to affect susceptibility to @entity4966 's @entity99 . This study was designed specifically to examine the contribution of statistically quantified variance in enzyme content and activity on the risk of @entity130 among adult @entity1 . We combined data sets describing (1) the microsomal protein content of @entity1 liver, (2) the @entity5321 content of @entity1 liver microsomal protein, and (3) the in vitro Vmax for @entity4966 oxidation by @entity1 . The 5th and 95th percentiles of the resulting distribution ( @entity4966 oxidized per minute per gram liver) differed by approximately sixfold. These values were converted to mg @entity4966 oxidized/h/kg body mass and incorporated in a @entity1 PBPK model. Simulations of 8-hour inhalation exposure to 50 ppm and oral exposure to 5 micro g @entity4966 /L in 2 L drinking water showed that the amount of @entity4966 oxidized in the liver differs by 2% or less under extreme values of @entity5321 expression and activity (here, selected as the 5th and 95th percentiles of the resulting distribution). This indicates that differences in enzyme expression and @entity4966 oxidation among the central 90% of the adult @entity1 population account for approximately 2% of the difference in production of the risk-relevant PK outcome for @entity4966 -mediated @entity99 . Integration of in vitro metabolism information into physiological models may reduce the uncertainties associated with risk contributions of differences in enzyme expression and the UF that represent PK variability.

title: The impact of @entity5321 -dependent metabolic variance on a risk-relevant pharmacokinetic outcome in XXXX .

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


abstract: OBJECTIVE: To propose terminology to distinguish cycles from episodes in @entity1 and adults with @entity162 ( @entity162 ). METHODS: To examine current definitions of rapid cycling and episodes in both @entity1 and adult @entity162 , an Internet search of the MEDLINE database was conducted. RESULTS: Investigations of rapid cycling in adults used the terms cycle and episode interchangeably to describe discrete periods of @entity1316 . Two studies of @entity1 and one study of adults with @entity162 , however, reported cycles occurring daily (ultradian cycling) or every few days (ultrarapid cycling). Without definitions to differentiate cycles from episodes, determining the overall duration of illness in subjects who experience ultrarapid or ultradian cycling is not possible. For example, a @entity1 cycled twice a day, every day, for 365 days (1 year). With the terminology currently in use, it is unclear whether this should be described as a single episode that had a duration of 365 days or as approximately 730 episodes (2 cycles per day x 365 days), each less than 24 hours in duration. Moreover, adults with @entity162 may have more intermittent pathology than @entity1 (e.g., adults may cycle 4 days per week, versus @entity1 may cycle 7 days per week). CONCLUSION: The following definitions are proposed. (1) Episodes will be defined by (a) the duration from onset to offset of a period of at least 2 weeks in length during which only one mood state persists or (b) the duration from onset to offset of a period of ultrarapid or ultradian cycling for at least 2 weeks. (2) Cycles will be defined by mood switches occurring daily or every few days during an episode. Further research will be needed to elucidate potential differences between @entity1 and adult cycling patterns.

title: Definitions of rapid, ultrarapid, and ultradian cycling and of episode duration in pediatric and adult XXXX : a proposal to distinguish episodes from cycles.

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

entities_list: @entity1316 :: ('MESH:D019964', 'Disease') :: ['mood disorders']

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

answer: @entity162 :: (MESH:D001714,Disease) :: ['bipolar disorders']


abstract: OBJECTIVE: To evaluate the role of gamma knife (GK) in the treatment of trigeminal @entity808 . METHODS: From June 1994 to June 2000, 38 @entity1 with trigeminal schwannoma treated with GK radiosurgery were reviewed. GK was the primary treatment modality in 30 cases and followed microsurgery in 8 cases. Of the 38 @entity5 , 12 had small cysts within the @entity5 , the rest were solid. The mean diameter of the 38 @entity5 was 32 mm (range: 16 approximately 48 mm) and the @entity5 ranged in volume from 2 to 33 cm(3) (with a mean mean volume of 9 cm(3)). The maximum dose irradiated to @entity5 was 20 to 33 Gy (mean: 26 Gy), the @entity5 margin dose ranged from 11 to 15 Gy (mean: 13 Gy). RESULTS: 35 @entity1 had been followed for 26 to 98 months (mean: 65 months). 20 had been followed more than 60 months. Mild @entity1183 or @entity892 relieved completely in 12 @entity1 after GK treatment. Improvement of @entity51 was seen in 11, unchanged dysfunction or slightly worsening of trigeminal nerve deficits in 9. Three @entity1 had mild worsened symptoms at different time because of @entity5 progression. @entity5 growth control: @entity5 disappeared after GK treatment was observed in 5 cases from 18 to 36 months after, a marked decrease in volume was observed in 24 cases, unchange in 2 cases and increase in 3 cases at 5, 26, and 60 months after respectively. One @entity1 with resolved symptom refused to have MRI examination for more than 6 years. Of the three increased @entity5 , one recurrent @entity5 elapsed 26 months after GK treatment. The second was a small @entity5 and started to progress 5 years after, but after second GK treatment, the @entity5 decreased again. The third was large @entity5 and was subtotally removed through surgery because of @entity5 swelling 5 months after. At last follow-up, the @entity41 remained stable. The control rate of the 35 @entity5 was 91% (32/35). CONCLUSION: Small and middle-size trigeminal @entity808 are the best candidates for GK radiosurgery. The control dose is 13 to 14 Gy.

title: [Gamma knife radiosurgery for trigeminal XXXX ].

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

entities_list: @entity41 :: ('MESH:D018365', 'Disease') :: ['residual tumor']

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

entities_list: @entity51 :: ('MESH:D009461', 'Disease') :: ['neurological deficits']

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

answer: @entity808 :: (MESH:D009442,Disease) :: ['schwannomas']


abstract: Type I (insulin dependent) @entity6 is usually believed to present acutely and it is assumed that metabolic decompensation is sudden. In a prospective family study, however, 10 of 13 subjects developing the disease showed progressive or intermittent development of hyperglycaemia over many months and the others had non-specific symptoms over a long period. All were first degree relatives of a @entity1 with @entity1723 ; 10 were siblings (aged 5-24) and three were parents (aged 45-58). All possessed HLA-DR4 or DR3, or both, and all but two had been positive for islet cell antibodies for six to 86 months before diagnosis. Ten had non-specific symptoms for two to 14 months before the onset of thirst and @entity2011 ; one remained asymptomatic even when insulin became necessary. Six subjects had an oral @entity413 tolerance test before clinical onset, of whom five were @entity6 by World Health Organisation criteria four, four, six, seven, and 21 months before insulin was needed. Nine showed random blood @entity413 concentrations above the 97.5th centile (6.3 mmol/l) six to 34 months (median 12) before diagnosis. Two others had a @entity413 tolerance test result compatible with @entity6 but had not reached the stage of needing insulin. Hyperglycaemia is often of insidious onset in @entity1723 , even in @entity1 and young adults. Diagnosis will inevitably be late if considered only when acute symptoms of thirst and @entity2011 develop.

title: Type I (insulin dependent) XXXX : a disease of slow clinical onset?

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

entities_list: @entity1723 :: ('MESH:D003922', 'Disease') :: ['type I diabetes']

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

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


abstract: BACKGROUND: Inhaled corticosteroids (ICSs) are well established as the mainstay of @entity565 therapy. A number of ICSs are now available, each with unique pharmacokinetic/pharmacodynamic profiles and physical characteristics. OBJECTIVE: This article reviews the key characteristics of an ideal @entity16179 and uses examples of existing agents to indicate the extent to which therapies reach these goals. RESULTS: Improved therapeutic efficacy in an @entity16179 may be offset by an increase in systemic effects. The ideal characteristics of an @entity16179 include optimal clinical efficacy and no @entity137 in combination with a convenient and easy-to-use inhaler device. To achieve this optimal profile, an @entity16179 should have the following: a high affinity for and potency at the @entity4738 ; prolonged retention in the lung; minimal or no oral bioavailability (ie, high first-pass inactivation); and rapid, complete systemic inactivation. The formulation and type of inhaler device are also important considerations: they should provide deposition in the lung in both large and small airways with no absorption effects outside the lung. ICSs should be evaluated for administration with several different delivery devices to ensure ease of use by @entity1 of all ages with different @entity565 severities. An @entity16179 that can be administered QD is also likely to improve @entity1 adherence by simplifying the treatment regimen. CONCLUSION: An ideal @entity16179 should have a large therapeutic margin, be used safely and effectively for long periods, be administered QD, be suitable for use in @entity1 of all ages and @entity565 severities, and offer both control and prevention of @entity565 symptoms and exacerbations.

title: Expected characteristics of an ideal, all-purpose inhaled corticosteroid for the treatment of XXXX .

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

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

entities_list: @entity4738 :: ('2908', 'Gene') :: ['glucocorticoid receptor']

answer: @entity565 :: (MESH:D001249,Disease) :: ['asthma']


abstract: Newborn @entity35 were administered the neurotoxin @entity2955 ( @entity2955 ) to determine whether neonatal ablation of the noradrenergic (NE) innervation produces augmented growth (i.e., sprouting) of serotonergic ( @entity750 ) raphe-cortical axons. Following NE denervation at birth, the density of @entity750 axons in motor cortex ( @entity15582 ) was determined at 4 days postnatal. Using a computer microscope system, the positions of all @entity750 -positive axons were mapped in radial strips of cortex from treated and control @entity35 . Cumulative axon length, expressed as a function of area inspected, was used as a parameter of innervation density. Following @entity2955 , the cumulative length of @entity750 axons in motor cortex increases by 32% (P less than 0.05) while cortical @entity750 levels measured by HPLC concomitantly increase by 29% (P less than 0.005). The combined increases in @entity750 axon density and in neurotransmitter levels indicate that NE denervation produces increased growth of the cortical @entity750 innervation by the 4th postnatal day. The amount of transmitter stored per unit length of @entity750 axons appears unchanged. In @entity2955 -treated @entity35 , @entity750 axons exhibit augmented growth in all layers of motor cortex. In the treated @entity35 , the relative density of @entity750 axons in each cortical layer is roughly proportional to the normal innervation density. Accordingly, in motor cortex, the magnitude of @entity750 axon sprouting is greatest in layer VI, which normally receives a dense @entity750 innervation, and is less in layer V, which has a lower innervation density. Qualitative assessment of other cortical areas following @entity2955 reveals that @entity750 axon density appears increased in cortical zones that normally receive a dense @entity750 innervation, while the density remains low in zones with sparse innervation. The absence of axonal sprouting is particularly striking in those zones which receive a dense NE innervation but are sparsely innervated by @entity750 axons. Thus, while @entity750 axons undergo sprouting, they do not appear to replace ablated NE terminals in areas with a sparse @entity750 innervation. Hence, normal laminar and regional specificity of @entity750 axons is preserved despite ablation of NE afferents. These data indicate that, while NE denervation may trigger serotonergic sprouting, competition between NE and @entity750 fibers for the same postsynaptic sites is not the main factor that regulates postnatal growth of these axonal projections. The present findings demonstrate that the early development of raphe-cortical projections is influenced by NE cortical innervation.(ABSTRACT TRUNCATED AT 400 WORDS)

title: XXXX induces serotonergic axon sprouting in cerebral cortex of newborn @entity35 .

entities_list: @entity2955 :: ('MESH:D016627', 'Chemical') :: ['6-hydroxydopamine', '6-OHDA']

answer: @entity2955 :: (MESH:D016627,Chemical) :: ['6-Hydroxydopamine']


abstract: Newborn @entity35 were administered the neurotoxin @entity2955 ( @entity2955 ) to determine whether neonatal ablation of the noradrenergic (NE) innervation produces augmented growth (i.e., sprouting) of serotonergic ( @entity750 ) raphe-cortical axons. Following NE denervation at birth, the density of @entity750 axons in motor cortex ( @entity15582 ) was determined at 4 days postnatal. Using a computer microscope system, the positions of all @entity750 -positive axons were mapped in radial strips of cortex from treated and control @entity35 . Cumulative axon length, expressed as a function of area inspected, was used as a parameter of innervation density. Following @entity2955 , the cumulative length of @entity750 axons in motor cortex increases by 32% (P less than 0.05) while cortical @entity750 levels measured by HPLC concomitantly increase by 29% (P less than 0.005). The combined increases in @entity750 axon density and in neurotransmitter levels indicate that NE denervation produces increased growth of the cortical @entity750 innervation by the 4th postnatal day. The amount of transmitter stored per unit length of @entity750 axons appears unchanged. In @entity2955 -treated @entity35 , @entity750 axons exhibit augmented growth in all layers of motor cortex. In the treated @entity35 , the relative density of @entity750 axons in each cortical layer is roughly proportional to the normal innervation density. Accordingly, in motor cortex, the magnitude of @entity750 axon sprouting is greatest in layer VI, which normally receives a dense @entity750 innervation, and is less in layer V, which has a lower innervation density. Qualitative assessment of other cortical areas following @entity2955 reveals that @entity750 axon density appears increased in cortical zones that normally receive a dense @entity750 innervation, while the density remains low in zones with sparse innervation. The absence of axonal sprouting is particularly striking in those zones which receive a dense NE innervation but are sparsely innervated by @entity750 axons. Thus, while @entity750 axons undergo sprouting, they do not appear to replace ablated NE terminals in areas with a sparse @entity750 innervation. Hence, normal laminar and regional specificity of @entity750 axons is preserved despite ablation of NE afferents. These data indicate that, while NE denervation may trigger serotonergic sprouting, competition between NE and @entity750 fibers for the same postsynaptic sites is not the main factor that regulates postnatal growth of these axonal projections. The present findings demonstrate that the early development of raphe-cortical projections is influenced by NE cortical innervation.(ABSTRACT TRUNCATED AT 400 WORDS)

title: @entity2955 induces serotonergic axon sprouting in cerebral cortex of newborn XXXX .

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


abstract: @entity1 B-cell @entity5 have been established in athymic, BALB/c @entity19 using the EBV-positive @entity2109 cell line Namalwa. One-hundred-one of 104 animals (97%) developed @entity5 10-14 days following s.c. injection of a mixture of 20 x 10(6) Namalwa and 5 X 10(6) irradiated @entity1 @entity1492 (HT-1080) cells. @entity5 developed at the site of injection and reached approximately 300 mm2 (product of cross-sectional diameters) after 21 days; no @entity3 were found. Histological analysis showed that @entity5 consisted solely of lymphoid cells. Immunofluorescence assays demonstrated that while 85% of the @entity5 cells retained reactivity with the monoclonal B-cell antibody BA-1, 96% retained reactivity with antibody BA-2 and 43% with BA-3. A similar reactivity profile was observed with cultured Namalwa cells. @entity5 were passaged serially 10 times without significant change in BA-1, BA-2, or BA-3 reactivity. Indirect immunofluorescence demonstrated that antibody BA-2 reached @entity5 cells within 2 h following i.p. injection; antigen modulation was not observed. These results demonstrate the suitability of this B-cell model for testing the in vivo efficacy and stability of anti-B-cell immunoconjugates.

title: Establishment of a XXXX B-cell tumor in athymic @entity19 .

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

entities_list: @entity2109 :: ('MESH:D002051', 'Disease') :: ['Burkitt lymphoma']

entities_list: @entity1492 :: ('MESH:D005354', 'Disease') :: ['fibrosarcoma']

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

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


abstract: @entity1 B-cell @entity5 have been established in athymic, BALB/c @entity19 using the EBV-positive @entity2109 cell line Namalwa. One-hundred-one of 104 animals (97%) developed @entity5 10-14 days following s.c. injection of a mixture of 20 x 10(6) Namalwa and 5 X 10(6) irradiated @entity1 @entity1492 (HT-1080) cells. @entity5 developed at the site of injection and reached approximately 300 mm2 (product of cross-sectional diameters) after 21 days; no @entity3 were found. Histological analysis showed that @entity5 consisted solely of lymphoid cells. Immunofluorescence assays demonstrated that while 85% of the @entity5 cells retained reactivity with the monoclonal B-cell antibody BA-1, 96% retained reactivity with antibody BA-2 and 43% with BA-3. A similar reactivity profile was observed with cultured Namalwa cells. @entity5 were passaged serially 10 times without significant change in BA-1, BA-2, or BA-3 reactivity. Indirect immunofluorescence demonstrated that antibody BA-2 reached @entity5 cells within 2 h following i.p. injection; antigen modulation was not observed. These results demonstrate the suitability of this B-cell model for testing the in vivo efficacy and stability of anti-B-cell immunoconjugates.

title: Establishment of a @entity1 B-cell tumor in athymic XXXX .

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


abstract: Circulatory disturbances may occur during and after the treatment of @entity981 ( @entity981 ). The reasons are: leukemic infiltrations of the heart, @entity417 , @entity8 , @entity1370 drugs, especially @entity8253 (Atc). The aim of the study was echocardiographic assessment of circulatory system in @entity1 during and 3-5 years after @entity981 therapy in childhood. The study group (group B) consisted of 20 @entity1 , aged 1-16 years, who underwent Atc treatment with cumulative doses 155.8-330 mg/m2 and cardioprotective agent-- @entity10976 . In this group echocardiography was performed before the treatment as well as after 1, 6, 12 months and 3 years. The retrospective group (R) consisted of 36 @entity1 aged 12-24 years, examined 3-5 years after the completion of @entity981 treatment, who had undergone the treatment with Atc in doses 148.6-416.7 mg/m2 without cardioprotection. The control group (K) consisted of 28 healthy volunteers, aged 9-25 years. In all subjects echocardiography was performed, standard measurements taken, systolic and diastolic indices of left ventricle (LV) function calculated. In @entity1 during and 3-5 years after the treatment neither LV dilatation nor abnormal wall-thickness was found. The systolic indices remained normal. In the group B echocardiographic indices did not change significantly during 3 years of treatment and did not correlate with growing cumulative Atc doses. In this group isovolumetric relaxation time (IVRT) was significantly longer, what emphasized the need of further clinical and echocardiographic follow-up.

title: [Echocardiographic assessment of circulation system in XXXX during and 3-5 years after all therapy in childhood].

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

entities_list: @entity8 :: ('MESH:D007674', 'Disease') :: ['renal disturbances, infections']

entities_list: @entity981 :: ('MESH:D054198', 'Disease') :: ['ALL', 'acute lymphoblastic leukemia']

entities_list: @entity8253 :: ('MESH:D018943', 'Chemical') :: ['anthracyclines']

entities_list: @entity1370 :: ('MESH:D066126', 'Disease') :: ['cardiotoxic']

entities_list: @entity10976 :: ('MESH:D011929', 'Chemical') :: ['dexrazoxane']

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


abstract: OBJECTIVE: To evaluate the efficacy and tolerability of the highly selective @entity3840 ( @entity3840 ) inhibitor @entity14296 for the treatment of @entity309 ( @entity309 ). METHODS: A double blind, randomized, placebo and active comparator controlled, 12 week study conducted at 88 US sites. Eligible @entity1 were chronic nonsteroidal antiinflammatory drug (NSAID) users with clinical worsening of @entity309 upon withdrawal of prestudy NSAID. @entity1 received either placebo, @entity14296 90 mg once daily, or @entity1623 500 mg twice daily (2:2:1 allocation ratio). Primary efficacy measures: @entity1 and investigator global assessments of disease activity and direct assessment of @entity625 by counts of tender and swollen joints. Key secondary measures: @entity1 global assessment of @entity158 , the Stanford Health Assessment Questionnaire, and the percentage of @entity1 both completing the study and meeting the ACR20 criteria. Tolerability was assessed by tabulation of adverse events and routine laboratory evaluations. RESULTS: In all, 816 @entity1 were randomized (placebo = 323, @entity14296 = 323, @entity1623 = 170), and 448 completed 12 weeks of treatment (placebo = 122, @entity14296 = 230, @entity1623 = 96). Compared with @entity1 receiving placebo, @entity1 receiving @entity14296 and @entity1623 showed significant improvements in all efficacy endpoints (p < 0.01). Compared with @entity1 receiving @entity1623 , @entity1 receiving @entity14296 demonstrated significant improvements (p < 0.05) on all primary endpoints and most other endpoints including ACR20 criteria. The percentage of @entity1 who achieved an ACR20 response and who completed the study was 21%, 53%, and 39% in the placebo, @entity14296 and @entity1623 groups, respectively. @entity14296 and @entity1623 were both generally well tolerated. CONCLUSION: In this study, @entity14296 90 mg once daily was more effective than either placebo or @entity1623 500 mg twice daily for treating @entity1 with @entity309 over 12 weeks. @entity14296 90 mg was generally well tolerated in @entity1 with @entity309 .

title: A randomized, controlled, clinical trial of XXXX in the treatment of @entity309 .

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

entities_list: @entity625 :: ('MESH:D001168', 'Disease') :: ['arthritis']

entities_list: @entity1623 :: ('MESH:D009288', 'Chemical') :: ['naproxen']

entities_list: @entity14296 :: ('MESH:C422649', 'Chemical') :: ['etoricoxib', 'Etoricoxib']

entities_list: @entity309 :: ('MESH:D001172', 'Disease') :: ['rheumatoid arthritis', 'RA']

answer: @entity14296 :: (MESH:C422649,Chemical) :: ['etoricoxib']


abstract: OBJECTIVE: To evaluate the efficacy and tolerability of the highly selective @entity3840 ( @entity3840 ) inhibitor @entity14296 for the treatment of @entity309 ( @entity309 ). METHODS: A double blind, randomized, placebo and active comparator controlled, 12 week study conducted at 88 US sites. Eligible @entity1 were chronic nonsteroidal antiinflammatory drug (NSAID) users with clinical worsening of @entity309 upon withdrawal of prestudy NSAID. @entity1 received either placebo, @entity14296 90 mg once daily, or @entity1623 500 mg twice daily (2:2:1 allocation ratio). Primary efficacy measures: @entity1 and investigator global assessments of disease activity and direct assessment of @entity625 by counts of tender and swollen joints. Key secondary measures: @entity1 global assessment of @entity158 , the Stanford Health Assessment Questionnaire, and the percentage of @entity1 both completing the study and meeting the ACR20 criteria. Tolerability was assessed by tabulation of adverse events and routine laboratory evaluations. RESULTS: In all, 816 @entity1 were randomized (placebo = 323, @entity14296 = 323, @entity1623 = 170), and 448 completed 12 weeks of treatment (placebo = 122, @entity14296 = 230, @entity1623 = 96). Compared with @entity1 receiving placebo, @entity1 receiving @entity14296 and @entity1623 showed significant improvements in all efficacy endpoints (p < 0.01). Compared with @entity1 receiving @entity1623 , @entity1 receiving @entity14296 demonstrated significant improvements (p < 0.05) on all primary endpoints and most other endpoints including ACR20 criteria. The percentage of @entity1 who achieved an ACR20 response and who completed the study was 21%, 53%, and 39% in the placebo, @entity14296 and @entity1623 groups, respectively. @entity14296 and @entity1623 were both generally well tolerated. CONCLUSION: In this study, @entity14296 90 mg once daily was more effective than either placebo or @entity1623 500 mg twice daily for treating @entity1 with @entity309 over 12 weeks. @entity14296 90 mg was generally well tolerated in @entity1 with @entity309 .

title: A randomized, controlled, clinical trial of @entity14296 in the treatment of XXXX .

answer: @entity309 :: (MESH:D001172,Disease) :: ['rheumatoid arthritis']


abstract: PURPOSE: To check for an association between @entity2049 ( @entity2050 ) use by the mother during pregnancy and @entity735 (i.e., @entity17347 , @entity4353 , and @entity4643 ) in the @entity1 , as suggested by Sutcliffe et al. (1998), who reported four cases. METHODS: We checked all the cases with these @entity735 for @entity2050 use by the mother in the EUROCAT Northern Netherlands dataset, which registers @entity1 with @entity600 and records possible teratogenic exposures (including medication taken by the mother). We also reviewed 13 studies in the literature. RESULTS: The EUROCAT dataset recorded 77 cases of @entity17347 , @entity4353 , or @entity4643 , but none with prenatal exposure to @entity2050 . Prenatal @entity2050 exposure was recorded in seven other cases without @entity735 . Large studies in the literature on the teratogenic effects of @entity2050 (and other antiepileptic drugs), including data from the MADRE database, revealed no association between these @entity735 and prenatal @entity2050 exposure. One case reported @entity17347 and other @entity154 after prenatal exposure to @entity2050 in combination with @entity5305 and @entity619 . CONCLUSIONS: Our data do not support Sutcliffe's suggestion that prenatal @entity2050 exposure may result in @entity735 . However, despite the large population represented, both the low birth prevalence of these @entity735 and the low prevalence of @entity2050 exposure during pregnancy make it difficult to exclude an increased relative risk. The many large prospective and retrospective studies in the literature seem to agree with our findings, although there is still uncertainty about the teratogenic effect of @entity2050 in polytherapy.

title: Is there an association between maternal @entity2049 use during pregnancy and @entity735 in the XXXX ?

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

entities_list: @entity154 :: ('MESH:D000013', 'Disease') :: ['congenital anomalies']

entities_list: @entity5305 :: ('MESH:D020888', 'Chemical') :: ['vigabatrin']

entities_list: @entity4353 :: ('MESH:D008850', 'Disease') :: ['microphthalmia']

entities_list: @entity600 :: ('MESH:D000014', 'Disease') :: ['congenital malformations']

entities_list: @entity735 :: ('MESH:D005124', 'Disease') :: ['congenital eye malformations', 'congenital eye malformation', 'eye malformations']

entities_list: @entity17347 :: ('MESH:D000853', 'Disease') :: ['anophthalmia', 'bilateral anophthalmia']

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

entities_list: @entity2049 :: ('MESH:D002220', 'Chemical') :: ['carbamazepine']

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


abstract: PURPOSE: To check for an association between @entity2049 ( @entity2050 ) use by the mother during pregnancy and @entity735 (i.e., @entity17347 , @entity4353 , and @entity4643 ) in the @entity1 , as suggested by Sutcliffe et al. (1998), who reported four cases. METHODS: We checked all the cases with these @entity735 for @entity2050 use by the mother in the EUROCAT Northern Netherlands dataset, which registers @entity1 with @entity600 and records possible teratogenic exposures (including medication taken by the mother). We also reviewed 13 studies in the literature. RESULTS: The EUROCAT dataset recorded 77 cases of @entity17347 , @entity4353 , or @entity4643 , but none with prenatal exposure to @entity2050 . Prenatal @entity2050 exposure was recorded in seven other cases without @entity735 . Large studies in the literature on the teratogenic effects of @entity2050 (and other antiepileptic drugs), including data from the MADRE database, revealed no association between these @entity735 and prenatal @entity2050 exposure. One case reported @entity17347 and other @entity154 after prenatal exposure to @entity2050 in combination with @entity5305 and @entity619 . CONCLUSIONS: Our data do not support Sutcliffe's suggestion that prenatal @entity2050 exposure may result in @entity735 . However, despite the large population represented, both the low birth prevalence of these @entity735 and the low prevalence of @entity2050 exposure during pregnancy make it difficult to exclude an increased relative risk. The many large prospective and retrospective studies in the literature seem to agree with our findings, although there is still uncertainty about the teratogenic effect of @entity2050 in polytherapy.

title: Is there an association between maternal XXXX use during pregnancy and @entity735 in the @entity1 ?

answer: @entity2049 :: (MESH:D002220,Chemical) :: ['carbamazepine']


abstract: PURPOSE: To check for an association between @entity2049 ( @entity2050 ) use by the mother during pregnancy and @entity735 (i.e., @entity17347 , @entity4353 , and @entity4643 ) in the @entity1 , as suggested by Sutcliffe et al. (1998), who reported four cases. METHODS: We checked all the cases with these @entity735 for @entity2050 use by the mother in the EUROCAT Northern Netherlands dataset, which registers @entity1 with @entity600 and records possible teratogenic exposures (including medication taken by the mother). We also reviewed 13 studies in the literature. RESULTS: The EUROCAT dataset recorded 77 cases of @entity17347 , @entity4353 , or @entity4643 , but none with prenatal exposure to @entity2050 . Prenatal @entity2050 exposure was recorded in seven other cases without @entity735 . Large studies in the literature on the teratogenic effects of @entity2050 (and other antiepileptic drugs), including data from the MADRE database, revealed no association between these @entity735 and prenatal @entity2050 exposure. One case reported @entity17347 and other @entity154 after prenatal exposure to @entity2050 in combination with @entity5305 and @entity619 . CONCLUSIONS: Our data do not support Sutcliffe's suggestion that prenatal @entity2050 exposure may result in @entity735 . However, despite the large population represented, both the low birth prevalence of these @entity735 and the low prevalence of @entity2050 exposure during pregnancy make it difficult to exclude an increased relative risk. The many large prospective and retrospective studies in the literature seem to agree with our findings, although there is still uncertainty about the teratogenic effect of @entity2050 in polytherapy.

title: Is there an association between maternal @entity2049 use during pregnancy and XXXX in the @entity1 ?

answer: @entity735 :: (MESH:D005124,Disease) :: ['eye malformations']


abstract: In the early stages of @entity3 , development of the disease is dependent on growth factors produced by the host. There are clinical situations associated with an increase in these factors, such as partial resection of metastasized liver. Given the important role of hepatotrophic factors in liver regeneration, we have studied the effect of partial hepatectomy on the development of residual micrometastases in the liver, and on the @entity5 as a whole. We used a @entity19 model in which a rabdomiosarcoma was established by subcutaneous inoculation of syngeneic @entity5 cells in male Wag @entity35 . Subsequently, the @entity5 was resected and/or a 40% hepatectomy was performed. The effect of these two surgical procedures on the @entity5 process was analyzed on the 25th and 35th days post-inoculation, and the percentage of regenerating hepatocytes was assessed. Both the tumorectomy and liver resection, when not combined, produced an increase in regional adenopathies without modifying the evolution of @entity3 in the liver. However, when @entity5 excision and partial hepatectomy were performed simultaneously, there was a net increase in the metastatic process. In addition to a rapid spread of the disease (lung, mediastinum, retroperitoneum), the number of liver metastases increased by 300%. This development coincided with a steep rise in the percentage of regenerating hepatocytes, which nearly doubled that of the group subjected only to liver resection. We conclude that liver resection, alone or combined with excision of the @entity5 , may enhance @entity5 progression, both locally and at the metastasic level.

title: [Effect of hepatic resection on development of liver XXXX ].

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'neoplastic process', 'primary tumor']

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

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


abstract: Significant conformational differences between native and recombinant horseradish peroxidase have been shown by @entity4463 planigraphy, which includes a method of thermal activation of @entity4463 followed by @entity535 analysis of the protein preparation. Comparison of radioactivity distribution among the @entity535 residues with the theoretical (calculated) accessibility shows that the recombinant enzyme is characterized by high hydrophobicity and compactness of folding. The protective role of oligosaccharides in native enzyme has been confirmed. An unexpected result of the study is a finding on high accessibility of a catalytic @entity3793 residue in solution. An effect of low dose (3 Gy) of irradiation on the accessibility of @entity535 residues has been unequivocally demonstrated. The data can be interpreted as swelling of the compact folding and increase in the surface hydrophilicity of the recombinant enzyme. In the case of native enzyme, irradiation does not cause remarkable changes in the accessibility of @entity535 residues indicating the possible extensive radical modification of the native enzyme in the life-course of the cell. The catalytic @entity3793 is an exception. It becomes inaccessible after the enzyme irradiation, while its accessibility in the recombinant enzyme increases. An additional observation of a 5-fold decrease in the rate constant towards @entity273 points to the destructive effect of irradiation on the @entity3884 bond network in the distal domain of the native enzyme molecule and partial collapse of the active site pocket.

title: Conformational differences between native and recombinant horseradish peroxidase revealed by XXXX planigraphy.

entities_list: @entity3884 :: ('MESH:D006859', 'Chemical') :: ['hydrogen']

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

entities_list: @entity3793 :: ('CHEBI:27570', 'Chemical') :: ['histidine']

entities_list: @entity273 :: ('MESH:D006861', 'Chemical') :: ['hydrogen peroxide']

entities_list: @entity4463 :: ('CHEBI:29304', 'Chemical') :: ['tritium']

answer: @entity4463 :: (CHEBI:29304,Chemical) :: ['tritium']


abstract: Among 16,401 subjects attending two health screenings, in 1969 and 1971, 176 showed hypercalcaemia on both occasions, i.e. serum @entity460 values above 2.60 mmol l-1. The prevalence of hypercalcaemia increased in @entity1 with advancing age and occurred in close to 3% of those above the age of 60, whilst in @entity1 it was found in less than 0.7% in all age groups. The mean serum @entity460 concentration in @entity1 above the age of 50 was significantly higher than in @entity1 . This observation could at least partly explain why @entity2742 ( @entity2742 ) is more often diagnosed in females. Only nine @entity1 were initially referred for neck exploration. Most of the others were not even notified of the biochemical disturbance and thus it was possible to study the serum @entity460 values in an unattended cohort until follow-up after 14 years. In the hypercalcaemic @entity1 there was little or no increase in serum @entity460 during these years. In no @entity1 did the serum @entity460 level rise above 3.0 mmol l-1. Altogether, 24 @entity1 from the initial cohort were subsequently operated on for primary @entity2742 but there were only two further cases of verified @entity2742 , which developed during the follow-up period, in those who had been clearly normocalcaemic at the health surveys. In conclusion, hypercalcaemia, presumably caused by primary @entity2742 , is common but apparently develops slowly and with little risk of a progressive rise of serum @entity460 concentrations.

title: Prevalence of hypercalcaemia in a health survey: a 14-year follow-up study of serum XXXX values.

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

entities_list: @entity2742 :: ('MESH:D006961', 'Disease') :: ['HPT', 'hyperparathyroidism']

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

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


abstract: According to recent studies, elevated @entity701 levels are associated with @entity2414 performance. This specific effect of @entity701 has been shown in several studies using pharmacological doses of @entity701 . The present study was designed to determine the effects of endogenously stimulated @entity701 secretion on memory performance in healthy middle-aged @entity1 . For psychological stress challenging, we employed the Trier Social Stress Test (TSST). Subjects were assigned to either the TSST or a non-stressful control condition. Declarative and non-declarative memory performance was measured by a combined priming-free-recall-task. No significant group differences were found for memory performance. Post hoc analyses of variance indicated that regardless of experimental condition the subjects with remarkably high @entity701 increase in response to the experimental procedure (high responders) showed increased memory performance in the declarative task compared to subjects with low @entity701 response (low responders). The results suggest that stress-induced @entity701 failed to impair memory performance. The results are discussed with respect to gender-specific effects and modulatory effects of the sympathetic nervous system and psychological variables.

title: Hypothalamic-pituitary-adrenal axis reactivity to psychological stress and memory in middle-aged XXXX : high responders exhibit enhanced declarative memory performance.

entities_list: @entity2414 :: ('MESH:D008569', 'Disease') :: ['impaired declarative memory']

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

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


abstract: The population of Pakistan has been reported to have the highest rate of @entity0 of any Asian population (excluding Jews in Israel) and one of the highest rates of @entity43 worldwide. To explore the contribution that genetic factors make to these high rates, we have conducted a case-control study of 341 case subjects with @entity0 , 120 case subjects with @entity43 , and 200 female control subjects from two major cities of Pakistan (Karachi and Lahore). The prevalence of @entity5345 or @entity2674 mutations among case subjects with @entity0 was 6.7% (95% confidence interval [CI] 4.1%-9.4%), and that among case subjects with @entity43 was 15.8% (95% CI 9.2%-22.4%). Mutations of the @entity5345 gene accounted for 84% of the mutations among case subjects with @entity43 and 65% of mutations among case subjects with @entity0 . The majority of detected mutations are unique to Pakistan. Five @entity5345 mutations ( @entity70942 , @entity70943 , @entity36858 , @entity70944 , and @entity70945 ) and one @entity2674 mutation ( @entity70946 ) were found in multiple case subjects and represent candidate founder mutations. The penetrance of deleterious mutations in @entity5345 and @entity2674 is comparable to that of Western populations. The cumulative risk of @entity5 to age 85 years in female first-degree relatives of @entity5345 -mutation-positive case subjects was 48% and was 37% for first-degree relatives of the @entity2674 -mutation-positive case subjects. A higher proportion of case subjects with @entity0 than of control subjects were the progeny of first-cousin marriages (odds ratio [OR] 2.1; 95% CI 1.4-3.3; P=.001). The effects of consanguinity were significant for case subjects with early-onset @entity0 (age <40 years) (OR=2.7; 95% CI 1.5-4.9; P=.0008) and case subjects with @entity43 (OR=2.4; 95% CI 1.4-4.2; P=.002). These results suggest that recessively inherited genes may contribute to @entity5344 risk in Pakistan.

title: Contribution of XXXX and @entity2674 mutations to @entity5344 in Pakistan.

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

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

entities_list: @entity5344 :: ('MESH:D061325', 'Disease') :: ['breast and ovarian cancer']

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

answer: @entity5345 :: (672,Gene) :: ['BRCA1']


abstract: The population of Pakistan has been reported to have the highest rate of @entity0 of any Asian population (excluding Jews in Israel) and one of the highest rates of @entity43 worldwide. To explore the contribution that genetic factors make to these high rates, we have conducted a case-control study of 341 case subjects with @entity0 , 120 case subjects with @entity43 , and 200 female control subjects from two major cities of Pakistan (Karachi and Lahore). The prevalence of @entity5345 or @entity2674 mutations among case subjects with @entity0 was 6.7% (95% confidence interval [CI] 4.1%-9.4%), and that among case subjects with @entity43 was 15.8% (95% CI 9.2%-22.4%). Mutations of the @entity5345 gene accounted for 84% of the mutations among case subjects with @entity43 and 65% of mutations among case subjects with @entity0 . The majority of detected mutations are unique to Pakistan. Five @entity5345 mutations ( @entity70942 , @entity70943 , @entity36858 , @entity70944 , and @entity70945 ) and one @entity2674 mutation ( @entity70946 ) were found in multiple case subjects and represent candidate founder mutations. The penetrance of deleterious mutations in @entity5345 and @entity2674 is comparable to that of Western populations. The cumulative risk of @entity5 to age 85 years in female first-degree relatives of @entity5345 -mutation-positive case subjects was 48% and was 37% for first-degree relatives of the @entity2674 -mutation-positive case subjects. A higher proportion of case subjects with @entity0 than of control subjects were the progeny of first-cousin marriages (odds ratio [OR] 2.1; 95% CI 1.4-3.3; P=.001). The effects of consanguinity were significant for case subjects with early-onset @entity0 (age <40 years) (OR=2.7; 95% CI 1.5-4.9; P=.0008) and case subjects with @entity43 (OR=2.4; 95% CI 1.4-4.2; P=.002). These results suggest that recessively inherited genes may contribute to @entity5344 risk in Pakistan.

title: Contribution of @entity5345 and @entity2674 mutations to XXXX in Pakistan.

answer: @entity5344 :: (MESH:D061325,Disease) :: ['breast and ovarian cancer']


abstract: The population of Pakistan has been reported to have the highest rate of @entity0 of any Asian population (excluding Jews in Israel) and one of the highest rates of @entity43 worldwide. To explore the contribution that genetic factors make to these high rates, we have conducted a case-control study of 341 case subjects with @entity0 , 120 case subjects with @entity43 , and 200 female control subjects from two major cities of Pakistan (Karachi and Lahore). The prevalence of @entity5345 or @entity2674 mutations among case subjects with @entity0 was 6.7% (95% confidence interval [CI] 4.1%-9.4%), and that among case subjects with @entity43 was 15.8% (95% CI 9.2%-22.4%). Mutations of the @entity5345 gene accounted for 84% of the mutations among case subjects with @entity43 and 65% of mutations among case subjects with @entity0 . The majority of detected mutations are unique to Pakistan. Five @entity5345 mutations ( @entity70942 , @entity70943 , @entity36858 , @entity70944 , and @entity70945 ) and one @entity2674 mutation ( @entity70946 ) were found in multiple case subjects and represent candidate founder mutations. The penetrance of deleterious mutations in @entity5345 and @entity2674 is comparable to that of Western populations. The cumulative risk of @entity5 to age 85 years in female first-degree relatives of @entity5345 -mutation-positive case subjects was 48% and was 37% for first-degree relatives of the @entity2674 -mutation-positive case subjects. A higher proportion of case subjects with @entity0 than of control subjects were the progeny of first-cousin marriages (odds ratio [OR] 2.1; 95% CI 1.4-3.3; P=.001). The effects of consanguinity were significant for case subjects with early-onset @entity0 (age <40 years) (OR=2.7; 95% CI 1.5-4.9; P=.0008) and case subjects with @entity43 (OR=2.4; 95% CI 1.4-4.2; P=.002). These results suggest that recessively inherited genes may contribute to @entity5344 risk in Pakistan.

title: Contribution of @entity5345 and XXXX mutations to @entity5344 in Pakistan.

answer: @entity2674 :: (675,Gene) :: ['BRCA2']


abstract: 1 The milk excretion of @entity11121 ( @entity25982 ) was studied from both breasts in @entity1 with @entity1271 (n = 12) and healthy volunteers (controls, n = 4) to investigate the hypothesis that milk transfer of @entity25982 is higher in mastitic than in non-mastitic breasts. 2 @entity1 were included according to clinical symptoms of @entity1271 . Milk (and serum from controls) were sampled 0, 1, 2, 3, 4, 6 and 8 h after a single oral dose of 1320 mg @entity25982 . @entity114 concentrations in milk and serum were measured by an agar diffusion technique. 3 Maximum milk concentrations (Cmax) of @entity25982 in @entity1 were higher (P less than 0.05) in mastitic than in non-mastitic breasts. The latter concentrations were higher (P less than 0.05) than those in breast milk from healthy controls. In milk from the @entity1271 @entity1 (both breasts) the Cmax was reached after 2 h with a subsequent rapid decline in concentration. In milk from the healthy controls the @entity25982 concentration reached a plateau after 4 h. The area under the milk concentration vs time curve (AUC0-8h) was not different for mastitic vs non-mastitic breast milk in @entity1 nor for mastitic vs control breast milk. This can be explained by higher rates of appearance and disappearance of @entity25982 in the breast milk of @entity1271 @entity1 compared with healthy controls. In mastitic breast milk there was a moderate (P less than 0.01) increase in @entity1372 and albumin compared with non-mastitic milk. However, milk @entity972 , @entity413 and @entity1132 values were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Milk transfer of @entity11121 during puerperal XXXX .

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

entities_list: @entity972 :: ('MESH:D011188', 'Chemical') :: ['potassium']

entities_list: @entity114 :: ('MESH:D010406', 'Chemical') :: ['Penicillin']

entities_list: @entity11121 :: ('MESH:D010404', 'Chemical') :: ['phenoxymethylpenicillin']

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

answer: @entity1271 :: (MESH:D008413,Disease) :: ['mastitis']


abstract: 1 The milk excretion of @entity11121 ( @entity25982 ) was studied from both breasts in @entity1 with @entity1271 (n = 12) and healthy volunteers (controls, n = 4) to investigate the hypothesis that milk transfer of @entity25982 is higher in mastitic than in non-mastitic breasts. 2 @entity1 were included according to clinical symptoms of @entity1271 . Milk (and serum from controls) were sampled 0, 1, 2, 3, 4, 6 and 8 h after a single oral dose of 1320 mg @entity25982 . @entity114 concentrations in milk and serum were measured by an agar diffusion technique. 3 Maximum milk concentrations (Cmax) of @entity25982 in @entity1 were higher (P less than 0.05) in mastitic than in non-mastitic breasts. The latter concentrations were higher (P less than 0.05) than those in breast milk from healthy controls. In milk from the @entity1271 @entity1 (both breasts) the Cmax was reached after 2 h with a subsequent rapid decline in concentration. In milk from the healthy controls the @entity25982 concentration reached a plateau after 4 h. The area under the milk concentration vs time curve (AUC0-8h) was not different for mastitic vs non-mastitic breast milk in @entity1 nor for mastitic vs control breast milk. This can be explained by higher rates of appearance and disappearance of @entity25982 in the breast milk of @entity1271 @entity1 compared with healthy controls. In mastitic breast milk there was a moderate (P less than 0.01) increase in @entity1372 and albumin compared with non-mastitic milk. However, milk @entity972 , @entity413 and @entity1132 values were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Milk transfer of XXXX during puerperal @entity1271 .

answer: @entity11121 :: (MESH:D010404,Chemical) :: ['phenoxymethylpenicillin']


abstract: BACKGROUND AND AIM: @entity1 with @entity356 have a poor prognosis and low survival rates. The aim of the present paper was to characterize cellular and molecular properties to provide insight into aspects of @entity5 progression in early compared with advanced @entity356 . METHODS: One hundred and nine graded @entity356 (early or advanced stage, undifferentiated or differentiated type) with paired non- @entity5 tissue were studied to define the correlation between apoptosis (morphology, terminal deoxyribonucleotidyl transferase-mediated @entity1977 -digoxigenin nick end-labeling), cell proliferation (Ki-67 expression, morphology) and expression and localization of two proteins frequently having altered expression in @entity5 , namely @entity876 and @entity517 . RESULTS: Overall, apoptosis was lower in early stage, differentiated and undifferentiated @entity356 compared with @entity5 . Cell proliferation was comparatively high in all stages. There was a high level of @entity876 positivity in all stages. Only the early- and @entity5 that were @entity876 positive had a significantly higher level of apoptosis (P < 0.05). Cell proliferation was significantly greater (P < 0.05) only in the early undifferentiated @entity5 that had either @entity517 or @entity876 -positivity. CONCLUSIONS: The results indicate that low apoptosis and high cell proliferation combine to drive @entity356 development. The molecular controls for high cell proliferation of the early stage undifferentiated @entity356 involve overexpression of both @entity876 and @entity517 . Overexpression of @entity876 may also control @entity5 development in that its expression is associated with higher levels of apoptosis in early and late-stage undifferentiated, @entity5 .

title: Apoptosis and cell proliferation in the development of @entity356 : associations with @entity517 and XXXX protein expression.

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

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'advanced-stage undifferentiated cancers', 'cancers', 'cancer', 'advanced-stage cancers']

entities_list: @entity356 :: ('MESH:D013274', 'Disease') :: ['gastric cancer', 'gastric cancers', 'gastric carcinomas']

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


abstract: BACKGROUND AND AIM: @entity1 with @entity356 have a poor prognosis and low survival rates. The aim of the present paper was to characterize cellular and molecular properties to provide insight into aspects of @entity5 progression in early compared with advanced @entity356 . METHODS: One hundred and nine graded @entity356 (early or advanced stage, undifferentiated or differentiated type) with paired non- @entity5 tissue were studied to define the correlation between apoptosis (morphology, terminal deoxyribonucleotidyl transferase-mediated @entity1977 -digoxigenin nick end-labeling), cell proliferation (Ki-67 expression, morphology) and expression and localization of two proteins frequently having altered expression in @entity5 , namely @entity876 and @entity517 . RESULTS: Overall, apoptosis was lower in early stage, differentiated and undifferentiated @entity356 compared with @entity5 . Cell proliferation was comparatively high in all stages. There was a high level of @entity876 positivity in all stages. Only the early- and @entity5 that were @entity876 positive had a significantly higher level of apoptosis (P < 0.05). Cell proliferation was significantly greater (P < 0.05) only in the early undifferentiated @entity5 that had either @entity517 or @entity876 -positivity. CONCLUSIONS: The results indicate that low apoptosis and high cell proliferation combine to drive @entity356 development. The molecular controls for high cell proliferation of the early stage undifferentiated @entity356 involve overexpression of both @entity876 and @entity517 . Overexpression of @entity876 may also control @entity5 development in that its expression is associated with higher levels of apoptosis in early and late-stage undifferentiated, @entity5 .

title: Apoptosis and cell proliferation in the development of XXXX : associations with @entity517 and @entity876 protein expression.

answer: @entity356 :: (MESH:D013274,Disease) :: ['gastric carcinomas']


abstract: BACKGROUND AND AIM: @entity1 with @entity356 have a poor prognosis and low survival rates. The aim of the present paper was to characterize cellular and molecular properties to provide insight into aspects of @entity5 progression in early compared with advanced @entity356 . METHODS: One hundred and nine graded @entity356 (early or advanced stage, undifferentiated or differentiated type) with paired non- @entity5 tissue were studied to define the correlation between apoptosis (morphology, terminal deoxyribonucleotidyl transferase-mediated @entity1977 -digoxigenin nick end-labeling), cell proliferation (Ki-67 expression, morphology) and expression and localization of two proteins frequently having altered expression in @entity5 , namely @entity876 and @entity517 . RESULTS: Overall, apoptosis was lower in early stage, differentiated and undifferentiated @entity356 compared with @entity5 . Cell proliferation was comparatively high in all stages. There was a high level of @entity876 positivity in all stages. Only the early- and @entity5 that were @entity876 positive had a significantly higher level of apoptosis (P < 0.05). Cell proliferation was significantly greater (P < 0.05) only in the early undifferentiated @entity5 that had either @entity517 or @entity876 -positivity. CONCLUSIONS: The results indicate that low apoptosis and high cell proliferation combine to drive @entity356 development. The molecular controls for high cell proliferation of the early stage undifferentiated @entity356 involve overexpression of both @entity876 and @entity517 . Overexpression of @entity876 may also control @entity5 development in that its expression is associated with higher levels of apoptosis in early and late-stage undifferentiated, @entity5 .

title: Apoptosis and cell proliferation in the development of @entity356 : associations with XXXX and @entity876 protein expression.

answer: @entity517 :: (4609,Gene) :: ['c-myc']


abstract: In this study, I have investigated the structure of the @entity35 brain @entity8683 during fetal development. There is a progressive decrease in the apparent molecular size of the brain alpha-subunit during development: 130K on day 16 of gestation, 126K at birth, and 120K in the adult. Glycosylation was investigated as a possible reason for the observed differences in the alpha-subunit molecular size. The results show that the developmental decrease in the brain alpha-subunit apparent molecular size is due to a parallel decrease in @entity3167 content. This was further confirmed by measuring the retention of autophosphorylated insulin receptors on @entity3505 germ agglutinin (WGA)-Sepharose. An inverse correlation between developmental age and retention of @entity7263 -labeled insulin receptors on the lectin column was observed. Insulin binding increases 6-fold between 16 and 20 days of gestation [61 +/- 25 (+/- SE) fmol/mg protein and 364 +/- 42 fmol/mg, respectively]. Thereafter, binding in brain membranes decreases to 150 +/- 20 fmol/mg by 2 days after birth, then reaches the adult level of 63 +/- 15 fmol/mg. In addition, the degree of insulin-stimulated autophosphorylation closely parallels the developmental changes in insulin binding. Between 16 and 20 days of fetal life, insulin-stimulated phosphorylation of the beta-subunit increases 6-fold. Thereafter, the extent of phosphorylation decreases rapidly, reaching adult values identical with those in 16-day-old fetal brain. These results suggest that the embryonic brain possesses competent insulin receptors whose expression changes markedly during fetal development. This information should be important in defining the role of insulin in the developing nervous system.

title: Developmental aspects of the @entity35 brain XXXX : loss of @entity3167 and fluctuation in number characterize fetal development.

entities_list: @entity3167 :: ('MESH:D019158', 'Chemical') :: ['sialic acid']

answer: @entity8683 :: (24954(Tax:10116),Gene) :: ['insulin receptor']


abstract: In this study, I have investigated the structure of the @entity35 brain @entity8683 during fetal development. There is a progressive decrease in the apparent molecular size of the brain alpha-subunit during development: 130K on day 16 of gestation, 126K at birth, and 120K in the adult. Glycosylation was investigated as a possible reason for the observed differences in the alpha-subunit molecular size. The results show that the developmental decrease in the brain alpha-subunit apparent molecular size is due to a parallel decrease in @entity3167 content. This was further confirmed by measuring the retention of autophosphorylated insulin receptors on @entity3505 germ agglutinin (WGA)-Sepharose. An inverse correlation between developmental age and retention of @entity7263 -labeled insulin receptors on the lectin column was observed. Insulin binding increases 6-fold between 16 and 20 days of gestation [61 +/- 25 (+/- SE) fmol/mg protein and 364 +/- 42 fmol/mg, respectively]. Thereafter, binding in brain membranes decreases to 150 +/- 20 fmol/mg by 2 days after birth, then reaches the adult level of 63 +/- 15 fmol/mg. In addition, the degree of insulin-stimulated autophosphorylation closely parallels the developmental changes in insulin binding. Between 16 and 20 days of fetal life, insulin-stimulated phosphorylation of the beta-subunit increases 6-fold. Thereafter, the extent of phosphorylation decreases rapidly, reaching adult values identical with those in 16-day-old fetal brain. These results suggest that the embryonic brain possesses competent insulin receptors whose expression changes markedly during fetal development. This information should be important in defining the role of insulin in the developing nervous system.

title: Developmental aspects of the @entity35 brain @entity8683 : loss of XXXX and fluctuation in number characterize fetal development.

answer: @entity3167 :: (MESH:D019158,Chemical) :: ['sialic acid']


abstract: In this study, I have investigated the structure of the @entity35 brain @entity8683 during fetal development. There is a progressive decrease in the apparent molecular size of the brain alpha-subunit during development: 130K on day 16 of gestation, 126K at birth, and 120K in the adult. Glycosylation was investigated as a possible reason for the observed differences in the alpha-subunit molecular size. The results show that the developmental decrease in the brain alpha-subunit apparent molecular size is due to a parallel decrease in @entity3167 content. This was further confirmed by measuring the retention of autophosphorylated insulin receptors on @entity3505 germ agglutinin (WGA)-Sepharose. An inverse correlation between developmental age and retention of @entity7263 -labeled insulin receptors on the lectin column was observed. Insulin binding increases 6-fold between 16 and 20 days of gestation [61 +/- 25 (+/- SE) fmol/mg protein and 364 +/- 42 fmol/mg, respectively]. Thereafter, binding in brain membranes decreases to 150 +/- 20 fmol/mg by 2 days after birth, then reaches the adult level of 63 +/- 15 fmol/mg. In addition, the degree of insulin-stimulated autophosphorylation closely parallels the developmental changes in insulin binding. Between 16 and 20 days of fetal life, insulin-stimulated phosphorylation of the beta-subunit increases 6-fold. Thereafter, the extent of phosphorylation decreases rapidly, reaching adult values identical with those in 16-day-old fetal brain. These results suggest that the embryonic brain possesses competent insulin receptors whose expression changes markedly during fetal development. This information should be important in defining the role of insulin in the developing nervous system.

title: Developmental aspects of the XXXX brain @entity8683 : loss of @entity3167 and fluctuation in number characterize fetal development.

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


abstract: The objective of this study was to evaluate the activity of efavirenz after the failure of a @entity5198 -containing regimen. This prospective study included 47 @entity1 with plasma @entity645 loads >1000 copies/ml, and who had received @entity5198 for at least 16 weeks, included in an efavirenz-based salvage regimen. The main outcome measure was virological response, defined as an @entity645 RNA level decrease of at least 1 log(10) copies/ml after 24 weeks, according to genotypic and phenotypic resistance to efavirenz. Phenotypic resistance was defined as a >10-fold increase in the IC(50). The median CD4(+) cell count was 236 x 10(6)/liter and the median @entity645 RNA level was 4.5 log(10) copies/ml. Mutations known to decrease susceptibility to nonnucleoside reverse transcriptase inhibitors were observed in 79% of @entity1 , predominantly at residues 181 (49%), 103 (40%), and 106 (19%), but phenotypic resistance to efavirenz was seen in 62% of cases. All the strains with the @entity19898 mutation showed high-level resistance to efavirenz, in contrast with 20% of those carrying exclusively the @entity24606 mutation. By week 24, 38% of @entity1 had responded and 19% had achieved an undetectable @entity645 load. Virological failure was observed in @entity1 with phenotypic resistance to efavirenz (67 vs. 11%; relative risk [RR], 4; 95% confidence interval [CI], 1.07-14.89; p = 0.04), or in presence of the @entity19898 mutation (52 vs. 17%; RR, 1.77; 95% CI, 1.12-2.79; p = 0.02), and these results remained unchanged after adjusting for @entity645 load, or by resistance to the accompanying drugs in the salvage regimen. A previous longer period of @entity5198 therapy was significantly associated with the emergence of efavirenz resistance (288 vs. 170 days, p < 0.01). We conclude that genotypic and/or phenotypic resistance assays permit the sequential use of nonnucleoside reverse transcriptase inhibitors in the clinical setting. Our data suggest that an early change after @entity5198 failure could avoid the emergence of efavirenz resistance.

title: Extent and importance of cross-resistance to efavirenz after XXXX failure.

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

entities_list: @entity5198 :: ('MESH:D019829', 'Chemical') :: ['nevirapine']

answer: @entity5198 :: (MESH:D019829,Chemical) :: ['nevirapine']


abstract: BACKGROUND: Although several investigators have described a milder form of @entity7383 ( @entity392 ), called @entity392 , little is known about the effect of light therapy in this group. The current study evaluates 3 weeks of open treatment with light therapy in @entity392 and @entity392 @entity1 . METHODS: Subjects with major or @entity308 according to DSM-IV with a seasonal pattern were recruited during the winter of 1998-1999 from clinic @entity1 and media advertising. Subjects were commenced on open treatment of morning light therapy, for 30 min daily using a new fluorescent light therapy unit that produced approximately 5,000 lux at a distance of 12 inches. The treatment lasted 3 weeks and at the end of the first and second week of treatment the duration of exposure could be increased to a maximum of 60 min at the discretion of the clinician. The @entity308 ( @entity392 ) was administered weekly to evaluate outcome. Response was defined in a variety of ways to reflect the fact that @entity392 subjects had milder symptoms. RESULTS: Forty-six @entity392 ( @entity392 , n = 29, @entity392 , n = 15) completed at least 2 weeks. Response rates were generally similar in @entity392 subjects (64-69%) and @entity392 (40-67%) @entity1 . There was a trend for longer exposure to be associated with better outcome. CONCLUSIONS: Light therapy may be an effective treatment for subjects with both @entity308 with a seasonal pattern. Optimal duration, for the light therapy unit used in this study, is likely 45-60 min daily.

title: A comparison of open treatment of seasonal XXXX with light therapy.

entities_list: @entity308 :: ('MESH:D003866', 'Disease') :: ['minor depression', 'major and minor depression', 'Structured Interview Guide for the Hamilton Depression Rating Scale-SAD version']

entities_list: @entity392 :: ('MESH:D014012', 'Disease') :: ['subjects entered treatment and 44', 'SAD', 'SIGH-SAD', 'subsyndromal SAD']

entities_list: @entity7383 :: ('MESH:D016574', 'Disease') :: ['seasonal affective disorder']

answer: @entity308 :: (MESH:D003866,Disease) :: ['major and minor depression']


abstract: OBJECTIVE: The purpose of this study was to clarify the significance of bivariate cytokeratin and DNA flow cytometry for analysis of the biologic @entity146 of resectable @entity1149 . METHODS: In 92 @entity1 who underwent curative operations, the DNA ploidy status and S-phase fractions of the @entity5 cell populations inside the @entity5 were analyzed by a cytokeratin gating technique with @entity982 -embedded specimens and were correlated with the surgical results. RESULTS: Ninety @entity5 yielded assessable DNA histograms. DNA diploidy was detected in 25 @entity5 with a mean S-phase fraction of 14.3% +/- 4.7%, and DNA aneuploidy was detected in 65 @entity5 with a mean S-phase fraction of 15.1% +/- 7.1%. The 5-year overall and recurrence-free survivals were 73.3% and 70.3%, respectively. Multivariate analysis showed that only @entity2802 staging was a prognostic factor after surgery. There was a negative correlation between the logarithms of S-phase fraction and the disease-free interval for 22 @entity1 with proven recurrence (P =.006). The @entity5 with high S-phase fractions recurred more rapidly than did those with low S-phase fractions. CONCLUSION: In a bivariate analysis of cytokeratin and DNA flow cytometry in resectable @entity1149 , the S-phase fraction appeared to be correlated with the disease-free interval. However, DNA ploidy and S-phase fraction were not predictive of either recurrence or survival after operation. Thus DNA flow cytometry may be of limited use for the analysis of the biologic @entity2 .

title: Ability of bivariate cytokeratin and deoxyribonucleic acid flow cytometry to determine the biologic @entity146 of resectable XXXX .

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

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

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

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

entities_list: @entity982 :: ('MESH:D010232', 'Chemical') :: ['paraffin']

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


abstract: OBJECTIVE: The purpose of this study was to clarify the significance of bivariate cytokeratin and DNA flow cytometry for analysis of the biologic @entity146 of resectable @entity1149 . METHODS: In 92 @entity1 who underwent curative operations, the DNA ploidy status and S-phase fractions of the @entity5 cell populations inside the @entity5 were analyzed by a cytokeratin gating technique with @entity982 -embedded specimens and were correlated with the surgical results. RESULTS: Ninety @entity5 yielded assessable DNA histograms. DNA diploidy was detected in 25 @entity5 with a mean S-phase fraction of 14.3% +/- 4.7%, and DNA aneuploidy was detected in 65 @entity5 with a mean S-phase fraction of 15.1% +/- 7.1%. The 5-year overall and recurrence-free survivals were 73.3% and 70.3%, respectively. Multivariate analysis showed that only @entity2802 staging was a prognostic factor after surgery. There was a negative correlation between the logarithms of S-phase fraction and the disease-free interval for 22 @entity1 with proven recurrence (P =.006). The @entity5 with high S-phase fractions recurred more rapidly than did those with low S-phase fractions. CONCLUSION: In a bivariate analysis of cytokeratin and DNA flow cytometry in resectable @entity1149 , the S-phase fraction appeared to be correlated with the disease-free interval. However, DNA ploidy and S-phase fraction were not predictive of either recurrence or survival after operation. Thus DNA flow cytometry may be of limited use for the analysis of the biologic @entity2 .

title: Ability of bivariate cytokeratin and deoxyribonucleic acid flow cytometry to determine the biologic XXXX of resectable @entity1149 .

answer: @entity146 :: (MESH:D001523,Disease) :: ['aggressiveness']


abstract: Microdeletions and microduplications, not visible by routine chromosome analysis, are a major cause of @entity1 @entity600 and @entity1032 . Novel high-resolution, whole-genome technologies can improve the diagnostic detection rate of these small @entity2008 . Array-based comparative genomic hybridization allows such a high-resolution screening by hybridizing differentially labeled test and reference DNAs to arrays consisting of thousands of genomic clones. In this study, we tested the diagnostic capacity of this technology using approximately 3,500 flourescent in situ hybridization-verified clones selected to cover the genome with an average of 1 clone per megabase (Mb). The sensitivity and specificity of the technology were tested in normal-versus-normal control experiments and through the screening of @entity1 with known microdeletion syndromes. Subsequently, a series of 20 cytogenetically normal @entity1 with @entity1032 and @entity4238 suggestive of a @entity2008 were analyzed. In this series, three microdeletions and two microduplications were identified and validated. Two of these genomic changes were identified also in one of the parents, indicating that these are large-scale genomic polymorphisms. Deletions and duplications as small as 1 Mb could be reliably detected by our approach. The percentage of false-positive results was reduced to a minimum by use of a dye-swap-replicate analysis, all but eliminating the need for laborious validation experiments and facilitating implementation in a routine diagnostic setting. This high-resolution assay will facilitate the identification of novel genes involved in @entity1 @entity1032 and/or @entity600 syndromes and will provide insight into the flexibility and plasticity of the @entity1 genome.

title: Array-based comparative genomic hybridization for the genomewide detection of submicroscopic XXXX .

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

entities_list: @entity1032 :: ('MESH:D008607', 'Disease') :: ['mental retardation']

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

entities_list: @entity4238 :: ('MESH:D057215', 'Disease') :: ['dysmorphisms']

entities_list: @entity2008 :: ('MESH:D002869', 'Disease') :: ['chromosomal abnormality', 'chromosomal abnormalities']

answer: @entity2008 :: (MESH:D002869,Disease) :: ['chromosomal abnormalities']


abstract: An endoglucanase gene of @entity27928 present on plasmid pRUCL150 and expressed in @entity526 was subcloned in plasmid pBR322. Plasmid pRUCL153 contained the smallest DNA insert (2.9 kb) with endoglucanase activity. The plasmids directed the synthesis of a mostly periplasmic enzyme in @entity526 and the level of enzyme activity was comparable in several strains. Analysis by non-denaturing @entity2975 gel electrophoresis of the endoglucanase produced with various recombinant plasmids showed that it was unique. The endoglucanase gene on plasmid pRUCL153 was localized by physical mapping of independent transposon Tn5 insertions. Hence, its size was estimated to be approx. 1.3 kb. In vivo radioactive labelling of plasmid-encoded proteins using minicells, followed by denaturing @entity2975 gel electrophoresis, allowed us to determine the size of the endoglucanase: Mr 40,000 for the precursor and Mr 38,000 for the mature enzyme. It was demonstrated that no cellulase operon, but a single gene, was cloned. The direction of transcription of the gene was determined by placing it under the control of the promoter of the lactose operon.

title: Characterization and expression in XXXX of an endoglucanase gene of Pseudomonas fluorescens subsp. @entity27928 .

entities_list: @entity27928 :: ('155077', 'Species') :: ['Pseudomonas fluorescens subsp. cellulosa']

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

entities_list: @entity526 :: ('562', 'Species') :: ['Escherichia coli', 'E. coli']

answer: @entity526 :: (562,Species) :: ['Escherichia coli']


abstract: An endoglucanase gene of @entity27928 present on plasmid pRUCL150 and expressed in @entity526 was subcloned in plasmid pBR322. Plasmid pRUCL153 contained the smallest DNA insert (2.9 kb) with endoglucanase activity. The plasmids directed the synthesis of a mostly periplasmic enzyme in @entity526 and the level of enzyme activity was comparable in several strains. Analysis by non-denaturing @entity2975 gel electrophoresis of the endoglucanase produced with various recombinant plasmids showed that it was unique. The endoglucanase gene on plasmid pRUCL153 was localized by physical mapping of independent transposon Tn5 insertions. Hence, its size was estimated to be approx. 1.3 kb. In vivo radioactive labelling of plasmid-encoded proteins using minicells, followed by denaturing @entity2975 gel electrophoresis, allowed us to determine the size of the endoglucanase: Mr 40,000 for the precursor and Mr 38,000 for the mature enzyme. It was demonstrated that no cellulase operon, but a single gene, was cloned. The direction of transcription of the gene was determined by placing it under the control of the promoter of the lactose operon.

title: Characterization and expression in @entity526 of an endoglucanase gene of Pseudomonas fluorescens subsp. XXXX .

answer: @entity27928 :: (155077,Species) :: ['cellulosa']


abstract: @entity43 is the most lethal of the gynaecological @entity5 , affecting approximately 1 in 75 @entity1 in the developed world. In most cases (>75%), the disease is disseminated beyond the ovary at diagnosis. For @entity1 with @entity5 , many clinicians agree that standard treatment should comprise six cycles of @entity1311 - @entity3003 . Randomised trials over the past 10 years have indicated the superiority of @entity1311 -based treatment and that @entity3003 is equivalent to @entity900 , but better tolerated. A recent trial has suggested that @entity1205 may be a better option than @entity1311 , with reduced @entity2359 and comparable efficacy. Overall treatment results remain unsatisfactory, since the median survival for these @entity1 is 2-3 years. Future progress may be made by addressing the following issues: Would sequential regimes be more effective? Intriguing results from two large randomised trials (ICON-3 and GOG-132) indicate that single agent @entity902 might well be incorporated into such regimes. Additionally, a range of other agents could be tested as part of first-line regimes, having demonstrated activity in relapsed @entity1 ; these include topotecan, @entity136 and liposomal @entity632 . Newer agents, such as cell signalling inhibitors have shown potential as single agents, but may be particularly effective in combination with current drugs. Real progress can be expected when a better understanding is achieved of the mechanisms underlying clinical drug resistance in @entity43 , and a close laboratory-clinical interaction is crucial.

title: XXXX : progress and continuing controversies in management.

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

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

entities_list: @entity632 :: ('MESH:D004317', 'Chemical') :: ['doxorubicin']

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

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'stage III-IV disease']

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

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

entities_list: @entity1311 :: ('MESH:D017239', 'Chemical') :: ['paclitaxel']

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

entities_list: @entity1205 :: ('MESH:C067311', 'Chemical') :: ['docetaxel']

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

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