abstract: @entity244 is characterized by three major disorders of spatial analysis: fixed gaze or psychic @entity912 , simultagnosia, and @entity2055 or misreaching. Most @entity1 with @entity244 generally do not show all three of these signs. The authors herein reported the more than four-year clinical course of a case (a 43-year-old @entity1 ) with @entity244 presenting these three disorders. The @entity1 also had a mild type of conduction @entity2026 , but his attentional, intellectual and memory functions were well preserved. SPECT showed @entity1779 in the bilateral parieto-occipital areas. Whereas rehabilitative intervention with process specific approach for the @entity73 seemed to be significantly ineffective, a functional adaptation approach successfully promoted the @entity1 's social participation. However, the present @entity1 could not help having to resign from his job. Additionally, double impairment of visual (including @entity2055 ) and language functions made it impossible for him to obtain a new work. Like the present case, those who have a higher @entity75 , but retain good physical ability can hardly receive the benefit of the social welfare system in Japan. Legislation addressing this problem is a matter of great urgency.

title: Rehabilitative intervention and social participation of a case with XXXX and @entity2026 .

answer: @entity244 :: (MESH:D014899,Disease) :: ['Balint's syndrome']


abstract: OBJECTIVE: We have attempted to determine serum levels of type IV collagen (IV-C), laminin (LM), prolylhydroxylase (PH), metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in @entity409 to elucidate the clinical significance of MMPs and TIMPs in the process of @entity1575 . METHODS: Serum samples were collected from 60 @entity1 with @entity409 caused by @entity1956 or C. Serum levels of IV-C, LM, PH, @entity17944 , and @entity16617 were measured by a one-step sandwich enzyme immunoassay using monoclonal antibodies. The values were correlated with @entity15803 ( @entity15803 ) scores of liver biopsy specimens. RESULTS: LM and IV-C levels markedly increased in parallel with the progression of the @entity409 . The @entity1476 and @entity1549 levels tended to increase in @entity3619 ( @entity3619 ), and significantly elevated in @entity1575 ( @entity1575 ). There was a positive correlation between the IV-C and @entity1476 levels, and the ratio of IV-C to @entity1476 levels was significantly elevated in @entity1575 . Both @entity2843 and @entity1552 levels were markedly increased in @entity1575 . The @entity15803 scores were positively correlated with the serum IV-C and @entity1476 levels. CONCLUSIONS: Serum IV-C and @entity1476 levels may be useful diagnostic markers for @entity1575 , since they increased in parallel with the progression of @entity409 . In addition, the imbalances between IV-C, LM, and @entity16617 as fibrogenic factors and @entity56408 as fibrolytic factors may lead to @entity1575 , especially in @entity82 .

title: Clinical significance of serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in XXXX .

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

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

entities_list: @entity1956 :: ('MESH:D006509', 'Disease') :: ['hepatitis B']

entities_list: @entity409 :: ('MESH:D008107', 'Disease') :: ['chronic liver disease']

entities_list: @entity15803 :: ('MESH:D009370', 'Disease') :: ['HAI', 'Histology Activity Index']

entities_list: @entity1575 :: ('MESH:D008103', 'Disease') :: ['LC', 'liver cirrhosis', 'hepatic fibrosis', 'fibrosis in chronic viral liver disease']

entities_list: @entity3619 :: ('MESH:D006521', 'Disease') :: ['CAH', 'chronic active hepatitis']

answer: @entity409 :: (MESH:D008107,Disease) :: ['chronic liver disease']


abstract: Chemotherapy remains a commonly used therapeutic approach for many @entity5 . Indeed chemotherapy is relatively effective for treatment of certain @entity5 and it may be the only therapy (besides radiotherapy) that is appropriate for certain @entity5 . However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant @entity1 . Unfortunately most of these drug transporter inhibitors have not proven effective for therapy. Recently the possibilities of more specific, targeted therapies have sparked the interest of clinical and basic researchers as approaches to kill @entity5 cells. However, there are also problems associated with these targeted therapies. Two key signaling pathways involved in the regulation of cell growth are the Ras/ @entity8496 / @entity8047 / @entity3963 and @entity10412 / @entity983 / @entity584 / @entity3470 pathways. Dysregulated signaling through these pathways is often the result of genetic alterations in critical components in these pathways as well as mutations in upstream growth factor receptors. Furthermore, these pathways may be activated by chemotherapeutic drugs and ionizing radiation. This review documents how their abnormal expression can contribute to drug resistance as well as resistance to targeted therapy. This review will discuss in detail @entity983 regulation as this is a critical @entity5 suppressor gene frequently dysregulated in @entity1 @entity5 which contributes to therapy resistance. Controlling the expression of these pathways could improve @entity5 therapy and ameliorate @entity1 health.

title: Therapeutic resistance resulting from mutations in @entity8496 / @entity8047 / @entity3963 and @entity10412 / XXXX / @entity584 / @entity3470 signaling pathways.

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

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

answer: @entity983 :: (5728,Gene) :: ['PTEN']


abstract: Chemotherapy remains a commonly used therapeutic approach for many @entity5 . Indeed chemotherapy is relatively effective for treatment of certain @entity5 and it may be the only therapy (besides radiotherapy) that is appropriate for certain @entity5 . However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant @entity1 . Unfortunately most of these drug transporter inhibitors have not proven effective for therapy. Recently the possibilities of more specific, targeted therapies have sparked the interest of clinical and basic researchers as approaches to kill @entity5 cells. However, there are also problems associated with these targeted therapies. Two key signaling pathways involved in the regulation of cell growth are the Ras/ @entity8496 / @entity8047 / @entity3963 and @entity10412 / @entity983 / @entity584 / @entity3470 pathways. Dysregulated signaling through these pathways is often the result of genetic alterations in critical components in these pathways as well as mutations in upstream growth factor receptors. Furthermore, these pathways may be activated by chemotherapeutic drugs and ionizing radiation. This review documents how their abnormal expression can contribute to drug resistance as well as resistance to targeted therapy. This review will discuss in detail @entity983 regulation as this is a critical @entity5 suppressor gene frequently dysregulated in @entity1 @entity5 which contributes to therapy resistance. Controlling the expression of these pathways could improve @entity5 therapy and ameliorate @entity1 health.

title: Therapeutic resistance resulting from mutations in @entity8496 / @entity8047 / @entity3963 and @entity10412 / @entity983 / @entity584 / XXXX signaling pathways.

answer: @entity3470 :: (21977(Tax:10090),Gene) :: ['mTOR']


abstract: Chemotherapy remains a commonly used therapeutic approach for many @entity5 . Indeed chemotherapy is relatively effective for treatment of certain @entity5 and it may be the only therapy (besides radiotherapy) that is appropriate for certain @entity5 . However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant @entity1 . Unfortunately most of these drug transporter inhibitors have not proven effective for therapy. Recently the possibilities of more specific, targeted therapies have sparked the interest of clinical and basic researchers as approaches to kill @entity5 cells. However, there are also problems associated with these targeted therapies. Two key signaling pathways involved in the regulation of cell growth are the Ras/ @entity8496 / @entity8047 / @entity3963 and @entity10412 / @entity983 / @entity584 / @entity3470 pathways. Dysregulated signaling through these pathways is often the result of genetic alterations in critical components in these pathways as well as mutations in upstream growth factor receptors. Furthermore, these pathways may be activated by chemotherapeutic drugs and ionizing radiation. This review documents how their abnormal expression can contribute to drug resistance as well as resistance to targeted therapy. This review will discuss in detail @entity983 regulation as this is a critical @entity5 suppressor gene frequently dysregulated in @entity1 @entity5 which contributes to therapy resistance. Controlling the expression of these pathways could improve @entity5 therapy and ameliorate @entity1 health.

title: Therapeutic resistance resulting from mutations in @entity8496 / @entity8047 / XXXX and @entity10412 / @entity983 / @entity584 / @entity3470 signaling pathways.

answer: @entity3963 :: (5594,Gene) :: ['ERK']


abstract: Chemotherapy remains a commonly used therapeutic approach for many @entity5 . Indeed chemotherapy is relatively effective for treatment of certain @entity5 and it may be the only therapy (besides radiotherapy) that is appropriate for certain @entity5 . However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant @entity1 . Unfortunately most of these drug transporter inhibitors have not proven effective for therapy. Recently the possibilities of more specific, targeted therapies have sparked the interest of clinical and basic researchers as approaches to kill @entity5 cells. However, there are also problems associated with these targeted therapies. Two key signaling pathways involved in the regulation of cell growth are the Ras/ @entity8496 / @entity8047 / @entity3963 and @entity10412 / @entity983 / @entity584 / @entity3470 pathways. Dysregulated signaling through these pathways is often the result of genetic alterations in critical components in these pathways as well as mutations in upstream growth factor receptors. Furthermore, these pathways may be activated by chemotherapeutic drugs and ionizing radiation. This review documents how their abnormal expression can contribute to drug resistance as well as resistance to targeted therapy. This review will discuss in detail @entity983 regulation as this is a critical @entity5 suppressor gene frequently dysregulated in @entity1 @entity5 which contributes to therapy resistance. Controlling the expression of these pathways could improve @entity5 therapy and ameliorate @entity1 health.

title: Therapeutic resistance resulting from mutations in @entity8496 / XXXX / @entity3963 and @entity10412 / @entity983 / @entity584 / @entity3470 signaling pathways.

answer: @entity8047 :: (5609,Gene) :: ['MEK']


abstract: Chemotherapy remains a commonly used therapeutic approach for many @entity5 . Indeed chemotherapy is relatively effective for treatment of certain @entity5 and it may be the only therapy (besides radiotherapy) that is appropriate for certain @entity5 . However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant @entity1 . Unfortunately most of these drug transporter inhibitors have not proven effective for therapy. Recently the possibilities of more specific, targeted therapies have sparked the interest of clinical and basic researchers as approaches to kill @entity5 cells. However, there are also problems associated with these targeted therapies. Two key signaling pathways involved in the regulation of cell growth are the Ras/ @entity8496 / @entity8047 / @entity3963 and @entity10412 / @entity983 / @entity584 / @entity3470 pathways. Dysregulated signaling through these pathways is often the result of genetic alterations in critical components in these pathways as well as mutations in upstream growth factor receptors. Furthermore, these pathways may be activated by chemotherapeutic drugs and ionizing radiation. This review documents how their abnormal expression can contribute to drug resistance as well as resistance to targeted therapy. This review will discuss in detail @entity983 regulation as this is a critical @entity5 suppressor gene frequently dysregulated in @entity1 @entity5 which contributes to therapy resistance. Controlling the expression of these pathways could improve @entity5 therapy and ameliorate @entity1 health.

title: Therapeutic resistance resulting from mutations in @entity8496 / @entity8047 / @entity3963 and @entity10412 / @entity983 / XXXX / @entity3470 signaling pathways.

answer: @entity584 :: (207,Gene) :: ['Akt']


abstract: Chemotherapy remains a commonly used therapeutic approach for many @entity5 . Indeed chemotherapy is relatively effective for treatment of certain @entity5 and it may be the only therapy (besides radiotherapy) that is appropriate for certain @entity5 . However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant @entity1 . Unfortunately most of these drug transporter inhibitors have not proven effective for therapy. Recently the possibilities of more specific, targeted therapies have sparked the interest of clinical and basic researchers as approaches to kill @entity5 cells. However, there are also problems associated with these targeted therapies. Two key signaling pathways involved in the regulation of cell growth are the Ras/ @entity8496 / @entity8047 / @entity3963 and @entity10412 / @entity983 / @entity584 / @entity3470 pathways. Dysregulated signaling through these pathways is often the result of genetic alterations in critical components in these pathways as well as mutations in upstream growth factor receptors. Furthermore, these pathways may be activated by chemotherapeutic drugs and ionizing radiation. This review documents how their abnormal expression can contribute to drug resistance as well as resistance to targeted therapy. This review will discuss in detail @entity983 regulation as this is a critical @entity5 suppressor gene frequently dysregulated in @entity1 @entity5 which contributes to therapy resistance. Controlling the expression of these pathways could improve @entity5 therapy and ameliorate @entity1 health.

title: Therapeutic resistance resulting from mutations in XXXX / @entity8047 / @entity3963 and @entity10412 / @entity983 / @entity584 / @entity3470 signaling pathways.

answer: @entity8496 :: (22882,Gene) :: ['Raf']


abstract: Chemotherapy remains a commonly used therapeutic approach for many @entity5 . Indeed chemotherapy is relatively effective for treatment of certain @entity5 and it may be the only therapy (besides radiotherapy) that is appropriate for certain @entity5 . However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant @entity1 . Unfortunately most of these drug transporter inhibitors have not proven effective for therapy. Recently the possibilities of more specific, targeted therapies have sparked the interest of clinical and basic researchers as approaches to kill @entity5 cells. However, there are also problems associated with these targeted therapies. Two key signaling pathways involved in the regulation of cell growth are the Ras/ @entity8496 / @entity8047 / @entity3963 and @entity10412 / @entity983 / @entity584 / @entity3470 pathways. Dysregulated signaling through these pathways is often the result of genetic alterations in critical components in these pathways as well as mutations in upstream growth factor receptors. Furthermore, these pathways may be activated by chemotherapeutic drugs and ionizing radiation. This review documents how their abnormal expression can contribute to drug resistance as well as resistance to targeted therapy. This review will discuss in detail @entity983 regulation as this is a critical @entity5 suppressor gene frequently dysregulated in @entity1 @entity5 which contributes to therapy resistance. Controlling the expression of these pathways could improve @entity5 therapy and ameliorate @entity1 health.

title: Therapeutic resistance resulting from mutations in @entity8496 / @entity8047 / @entity3963 and XXXX / @entity983 / @entity584 / @entity3470 signaling pathways.

answer: @entity10412 :: (5293,Gene) :: ['PI3K']


abstract: BACKGROUND: Light-coloured and savoury-tasting flavour enhancers are attractive to both consumers and food producers. The aim of this study was to investigate the colour-inhibiting effect of @entity462 and @entity9138 during the Maillard reaction of @entity1460 peptide and @entity6122 . The correlation between volatile compounds and antioxidant activity of the corresponding products was also studied. RESULTS: Colour formation was markedly suppressed by @entity462 . Compared with peptide/xylose (PX), the taste profile of Maillard reaction products (MRPs) derived from peptide/xylose/ @entity462 (PXC) and peptide/xylose/ @entity462 / @entity9138 (PXCT) was stronger, including umami, mouthfulness, continuity, meaty and overall acceptance. PXC and PXCT also exihibited distinctly higher antioxidant activity. Principal component analysis was applied to investigate the correlation between antioxidant activity and volatile compounds. Of 88 volatile compounds identified, 55 were significantly correlated with antioxidant activity by two principal components (accounting for 85.05% of the total variance). CONCLUSION: Effective colour control of the Maillard reaction by @entity462 may allow the production of healthier (higher antioxidant activity) and tastier foods to satisfy consumers' and food producers' demands. Light-coloured products might be used as functional flavour enhancers in various food systems.

title: Contribution of sulfur-containing compounds to the colour-inhibiting effect and improved antioxidant activity of Maillard reaction products of XXXX protein hydrolysates.

entities_list: @entity462 :: ('MESH:D003545', 'Chemical') :: ['cysteine', 'L-cysteine']

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

answer: @entity1460 :: (3847,Species) :: ['soybean']


abstract: @entity2779 is a Class I antiarrhythmic agent with weak beta-adrenoceptor antagonist activity which can be given both intravenously and orally. Dosage must be individualised because of dose-dependent pharmacokinetics, a wide range of clinically effective plasma concentrations (64 to 3271 micrograms/L) after comparable doses, the presence of an active metabolite ( @entity73163 ) and genetically determined metabolic oxidation. In non-comparative studies @entity2779 450 and 900 mg/day orally significantly suppressed @entity1540 in 96% and 75% of @entity1 , respectively, and abolished @entity1165 in 75% of @entity1 . Efficacy was confirmed in placebo-controlled studies in which @entity2779 300 to 900mg daily suppressed @entity1540 (greater than 80%) in 77% of @entity1 ; 87% of @entity1 had significant reductions in couplets and abolition of @entity1165 . In @entity1 with @entity943 refractory to other antiarrhythmic agents, @entity2779 450 to 1200 mg/day suppressed @entity943 in 63% of @entity1 (in long term therapy 66%). Electrically induced @entity943 were prevented by intravenously administered @entity2779 in 12 to 23% of @entity1 . However, long term oral therapy was effective in 77% of @entity1 selected using programmed electrical stimulation. @entity2779 was also effective in suppressing atrial and AV nodal/junctional re-entrant @entity591 involving accessory pathways. A limited number of comparisons with other antiarrhythmic drugs indicate that the antiarrhythmic efficacy of @entity2779 is superior or similar to that of @entity5126 , @entity7306 and @entity11797 , and comparable to that of @entity3303 ( @entity3303 ), @entity6237 and @entity1406 against @entity943 and a smaller number of @entity943 . Cardiovascular side effects indicate a proarrhythmic effect similar to that with other Class I drugs, occasional precipitation of @entity712 and conduction abnormalities; the latter two occur more often in @entity1 with underlying @entity67 . Non-cardiovascular side effects (neurological, gastrointestinal) are well tolerated and generally resolve with continued therapy or dosage reduction. Thus, @entity2779 is an effective antiarrhythmic agent, and is a useful addition to currently available drugs, although further studies will be required to determine clearly its place in therapy compared with more established antiarrhythmic drugs.

title: @entity2779 . A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of XXXX .

entities_list: @entity712 :: ('MESH:D006333', 'Disease') :: ['congestive heart failure']

entities_list: @entity1165 :: ('MESH:D017180', 'Disease') :: ['ventricular tachycardia']

entities_list: @entity11797 :: ('MESH:D016677', 'Chemical') :: ['tocainide']

entities_list: @entity591 :: ('MESH:D013610', 'Disease') :: ['tachycardias and Wolff-Parkinson-White tachycardias']

entities_list: @entity73163 :: ('MESH:C044307', 'Chemical') :: ['5-hydroxy-propafenone']

entities_list: @entity6237 :: ('MESH:D005424', 'Chemical') :: ['flecainide']

entities_list: @entity3303 :: ('MESH:D008012', 'Chemical') :: ['lignocaine', 'lidocaine']

entities_list: @entity5126 :: ('MESH:D011802', 'Chemical') :: ['quinidine']

entities_list: @entity7306 :: ('MESH:D004206', 'Chemical') :: ['disopyramide']

entities_list: @entity1540 :: ('MESH:D018879', 'Disease') :: ['premature ventricular complexes', 'premature ventricular complexes and couplets']

entities_list: @entity1406 :: ('MESH:D008790', 'Chemical') :: ['metoprolol']

entities_list: @entity67 :: ('MESH:D018754', 'Disease') :: ['ventricular dysfunction']

entities_list: @entity943 :: ('MESH:D001145', 'Disease') :: ['atrial arrhythmias', 'ventricular arrhythmias', 'arrhythmias']

entities_list: @entity2779 :: ('MESH:D011405', 'Chemical') :: ['Propafenone', 'propafenone']

answer: @entity943 :: (MESH:D001145,Disease) :: ['arrhythmias']


abstract: @entity2779 is a Class I antiarrhythmic agent with weak beta-adrenoceptor antagonist activity which can be given both intravenously and orally. Dosage must be individualised because of dose-dependent pharmacokinetics, a wide range of clinically effective plasma concentrations (64 to 3271 micrograms/L) after comparable doses, the presence of an active metabolite ( @entity73163 ) and genetically determined metabolic oxidation. In non-comparative studies @entity2779 450 and 900 mg/day orally significantly suppressed @entity1540 in 96% and 75% of @entity1 , respectively, and abolished @entity1165 in 75% of @entity1 . Efficacy was confirmed in placebo-controlled studies in which @entity2779 300 to 900mg daily suppressed @entity1540 (greater than 80%) in 77% of @entity1 ; 87% of @entity1 had significant reductions in couplets and abolition of @entity1165 . In @entity1 with @entity943 refractory to other antiarrhythmic agents, @entity2779 450 to 1200 mg/day suppressed @entity943 in 63% of @entity1 (in long term therapy 66%). Electrically induced @entity943 were prevented by intravenously administered @entity2779 in 12 to 23% of @entity1 . However, long term oral therapy was effective in 77% of @entity1 selected using programmed electrical stimulation. @entity2779 was also effective in suppressing atrial and AV nodal/junctional re-entrant @entity591 involving accessory pathways. A limited number of comparisons with other antiarrhythmic drugs indicate that the antiarrhythmic efficacy of @entity2779 is superior or similar to that of @entity5126 , @entity7306 and @entity11797 , and comparable to that of @entity3303 ( @entity3303 ), @entity6237 and @entity1406 against @entity943 and a smaller number of @entity943 . Cardiovascular side effects indicate a proarrhythmic effect similar to that with other Class I drugs, occasional precipitation of @entity712 and conduction abnormalities; the latter two occur more often in @entity1 with underlying @entity67 . Non-cardiovascular side effects (neurological, gastrointestinal) are well tolerated and generally resolve with continued therapy or dosage reduction. Thus, @entity2779 is an effective antiarrhythmic agent, and is a useful addition to currently available drugs, although further studies will be required to determine clearly its place in therapy compared with more established antiarrhythmic drugs.

title: XXXX . A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of @entity943 .

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

answer: @entity2779 :: (MESH:D011405,Chemical) :: ['Propafenone']


abstract: T3 stimulates in vitro GH secretion, whereas @entity7750 have been shown to suppress GH. We, therefore, tested the effects of a recombinant @entity1 @entity442 ; Thr 59) on T3-induced GH secretion. Pituitary monolayer cultures were derived from 4- to 7-week surgically thyroidectomized male @entity35 and grown in hypothyroid medium stripped of T3 and T4. @entity1375 pituitary cell monolayers secreted low levels of GH (200 ng/ml X 72 h). GH secretion was stimulated (185% of T3-free controls) by the addition of T3 (0.1 nM) during 48 h of incubation. @entity2135 (up to 13 nM) did not alter basal GH secretion, but inhibited the induction of GH by T3. @entity2135 (0.65 nM) suppressed the 3.5-fold induction of GH by 0.25 nM T3 by 35% (p less than 0.001), whereas maximal (68%) GH suppression was seen with 6.5 nM @entity2135 (p less than 0.001). The inhibition of T3-induced GH by @entity2135 occurred after 24 h. By 72 h, @entity2135 (3.25 nM) suppressed GH stimulation by up to 1 nM T3 [213 +/- 12 (+/- SE) vs. 88 +/- 8 ng GH/10(4) cells]. Insulin, epidermal growth factor, and fibroblast growth factor did not alter the T3-induced GH secretion. GH mRNA was measured by agarose gel blot hybridization analysis and nitrocellulose dot blot hybridization of cytoplasmic RNA with @entity35 GH [32P]cDNA. T3 (0.25 nM) stimulated the hybridization of immobilized pituitary cell RNA extracts, indicating an almost 3-fold increase in @entity35 (r) GH mRNA levels; @entity2135 (3.25 nM) suppressed the T3-induced rGH mRNA content of pituitary cells from thyroidectomized @entity35 by 50% during 72 h of incubation. Maximal suppression of rGH mRNA induced by 0.25 nM T3 was achieved with 6.5 nM @entity2135 (35% of T3-treated cells). These results show that @entity2135 does not alter low basal GH secretion in pituitary cells from hypothyroid @entity35 . @entity2135 does, however, block the T3-induction of GH secretion and suppresses GH mRNA levels stimulated by T3. As T3 is known to directly stimulate GH gene transcription, @entity2135 may suppress T3 action on GH at a posttranscriptional site.

title: Insulin-like growth factor-I action on hypothyroid XXXX pituitary cells: suppression of triiodothyronine-induced growth hormone secretion and messenger ribonucleic acid levels.

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

entities_list: @entity7750 :: ('MESH:D013002', 'Chemical') :: ['somatomedins']

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

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


abstract: A collaborative group of @entity5 registries and hospitals carried out a case-control study of @entity5 of the bladder in @entity1 who had previously been treated for @entity43 . A total of 63 cases of @entity150 were identified, and 188 controls were selected matching for age, year of @entity43 diagnosis and survival time. Full details of the treatment for @entity43 were sought for both cases and for controls. The risk of @entity150 was increased for @entity1 who had been treated by radiotherapy alone (1.9; 95% confidence interval, 0.77-4.9), by chemotherapy alone (3.2; 0.97-10), and by chemotherapy and radiotherapy (5.2; 1.6-16), when comparison was made with @entity1 treated only by surgery. @entity1 treated by chemotherapy were separated into 2 groups according to whether they had received @entity786 . Among those who had, there was a clear increase in risk (approximately 4-fold) regardless of whether or not they had also received radiotherapy. For those who received only other drugs, risk was increased substantially among @entity1 who had also been treated by radiation, as compared with @entity1 treated by surgery alone, and those who had received radiotherapy only. Both melphalan and thiotepa were implicated as potential bladder carcinogens on the basis of these results. The estimated risk of @entity150 due to @entity786 was more than twice the risk following radiation to the bladder, and it appeared substantially earlier. For both agents, the risk continued to increase more than 10 years after treatment began.

title: Bladder XXXX following chemotherapy and radiotherapy for @entity43 : a case-control study.

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

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

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

entities_list: @entity786 :: ('MESH:D003520', 'Chemical') :: ['cyclophosphamide']

entities_list: @entity150 :: ('MESH:D001749', 'Disease') :: ['bladder tumours']

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


abstract: A collaborative group of @entity5 registries and hospitals carried out a case-control study of @entity5 of the bladder in @entity1 who had previously been treated for @entity43 . A total of 63 cases of @entity150 were identified, and 188 controls were selected matching for age, year of @entity43 diagnosis and survival time. Full details of the treatment for @entity43 were sought for both cases and for controls. The risk of @entity150 was increased for @entity1 who had been treated by radiotherapy alone (1.9; 95% confidence interval, 0.77-4.9), by chemotherapy alone (3.2; 0.97-10), and by chemotherapy and radiotherapy (5.2; 1.6-16), when comparison was made with @entity1 treated only by surgery. @entity1 treated by chemotherapy were separated into 2 groups according to whether they had received @entity786 . Among those who had, there was a clear increase in risk (approximately 4-fold) regardless of whether or not they had also received radiotherapy. For those who received only other drugs, risk was increased substantially among @entity1 who had also been treated by radiation, as compared with @entity1 treated by surgery alone, and those who had received radiotherapy only. Both melphalan and thiotepa were implicated as potential bladder carcinogens on the basis of these results. The estimated risk of @entity150 due to @entity786 was more than twice the risk following radiation to the bladder, and it appeared substantially earlier. For both agents, the risk continued to increase more than 10 years after treatment began.

title: Bladder @entity5 following chemotherapy and radiotherapy for XXXX : a case-control study.

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


abstract: Protectin ( @entity1009 ) is a glycolipid-anchored inhibitor of the membrane attack complex (MAC) of @entity1 complement (C) that protects blood cells, endothelial cells and various epithelial cells from C-mediated lysis. Because of its activities protectin is a candidate molecule for use in the treatment of @entity7965 or conditions where MAC causes tissue damage. Soluble, phospholipid-free forms of protectin have been isolated from @entity1 urine and produced in recombinant form, but they have only a relatively weak C lysis-inhibiting activity. In the present study we have looked for functionally active protectin in @entity1 breast milk. Milk is rich in fat droplets, milk fat globules (MFG), that are enveloped in a plasma membrane derived from secretory cells of the mammary gland. The membranes of MFG contain a variety of glycoproteins expressed by the mammary epithelial cells. Both immunofluorescence and immunoblotting analysis demonstrated that protectin was strongly expressed on @entity1 MFG. In @entity214 - @entity2975 gel electrophoresis ( @entity214 -PAGE) analysis, MFG protectin (CD59M) appeared as distinct bands with apparent molecular weights of 19,000-23,000 MW, similar to protectin extracted from MCF7 @entity0 cells. CD59M in breast milk was functionally active and had a glycophospholipid anchor, as judged by its ability to incorporate into @entity840 erythrocytes and inhibit their lysis by @entity1 complement. These results indicate that functionally active protectin becomes enriched in MFG and imply that secretion of glycophospholipid-anchored molecules, e.g. into @entity291 milk and colostrum, could be exploited as a means of producing bioactive molecules that need to be targeted into cell membranes.

title: Shedding and enrichment of the glycolipid-anchored complement lysis inhibitor protectin ( XXXX ) into milk fat globules.

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

entities_list: @entity7965 :: ('MESH:D006457', 'Disease') :: ['paroxysmal nocturnal haemoglobinuria']

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

entities_list: @entity214 :: ('CHEBI:8984', 'Chemical') :: ['sodium dodecyl sulphate', 'SDS']

answer: @entity1009 :: (966,Gene) :: ['CD59']


abstract: The completion of excision repair patches in @entity1 cells, following UV irradiation, was compared to the refolding of these regions into nucleosomes. Incomplete repair patches were detected by their enhanced sensitivity to exonuclease III. This enhanced sensitivity was due to the presence of gaps (or displaced parental strands) at the 3' end rather than unligated nicks, indicating that ligation occurs rapidly after repair synthesis is completed. Different rates of completion were achieved by treatment with the inhibitors @entity1862 and @entity11413 , as well as by using a (partially) ligase-deficient @entity1 cell strain. @entity1862 caused a marked decrease in both the rate of completion and the level of repair incorporation in all three cell types studied, while @entity11413 yielded different effects in each cell type. In each case, however, a decrease in the rate of repair patch completion resulted in a concomitant decrease in the level of nucleosome formation. To determine the temporal relationship of these two events, the levels of repair-incorporated @entity2036 in isolated 146-base pair nucleosome core DNA were compared on native and denaturing gels. The data indicate that little (or no) nucleosome formation occurred in the nascent DNA regions prior to ligation regardless of the cell type or treatment used. Furthermore, comparison of the fraction of unligated repair patches and the fraction of repair patches in a nonnucleosomal state indicated that in the absence of inhibitors there was a significant time lag between ligation and nucleosome formation. This lag time, however, decreased when cells were treated with @entity1862 . Thus, the formation of nucleosomes in newly repaired regions of DNA occurred after the ligation step in all cases and these two features of the excision repair process are not "tightly coupled" events.

title: Completion of excision repair in XXXX cells. Relationship between ligation and nucleosome formation.

entities_list: @entity2036 :: ('MESH:D009711', 'Chemical') :: ['nucleotides']

entities_list: @entity11413 :: ('CHEBI:64103', 'Chemical') :: ['sodium butyrate']

entities_list: @entity1862 :: ('MESH:D006918', 'Chemical') :: ['Hydroxyurea', 'hydroxyurea']

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


abstract: The mode by which coral snake (Micrurus nigrocinctus) venom affects skeletal muscle was studied using a combined approach. The venom induced early functional and structural alterations in the plasma membrane of muscle cells, suggesting that sarcolemma is the primary site of action of this venom. This was shown by the presence of wedge-shaped ('delta') lesions at the periphery of the cells, as well as by focal disruptions in the continuity of plasma membrane as early as 15 min after envenomation. After this initial alteration the rest of the organelles were severely affected. Myofilaments were hypercontracted leaving, as a consequence, areas of overstretched myofibrils as well as empty spaces. Eventually, myofilaments formed dense, clumped masses in which the striated structure was totally lost. At 24 h, myofilaments were still disorganized but they presented a more hyaline and homogeneous appearance. As early as 15 and 30 min mitochondria were swollen; later, by I, 3 and 24 h, they showed further alterations such as the presence of dense intracristal spaces and vesiculated cristae, as well as disruption in the integrity of their membranes. Sarcoplasmic reticulum was dilated and disorganized into many small vesicles randomly distributed throughout the cellular space. Moreover, the venom induced a rapid decrease in muscle levels of @entity908 and @entity908 -kinase (CK) and a @entity460 influx. Since the rates of efflux of @entity908 and CK were similar, it is suggested that the lesions produced in the membrane are large enough to allow the escape of these two molecules. As corroboration of the severe myotoxic effect, envenomated @entity19 excreted reddish urine containing large quantities of myoglobin. Skeletal muscle cells are more susceptible to the action of the venom than erythrocytes, since coral snake venom induced only a mild direct haemolytic effect in vitro and haemolysis is not a significant effect in vivo. M. nigrocinctus venom induced a drastic increase in plasma levels of @entity880 dehydrogenase. Isozymes @entity73164 , LDH-4, and LDH-5 increased markedly, suggesting that the systemic pathology of coral snake envenoming may be more complex than previously thought.

title: Pathogenesis of myonecrosis induced by coral snake (Micrurus nigrocinctus) venom in XXXX .

entities_list: @entity908 :: ('MESH:D003401', 'Chemical') :: ['creatine']

entities_list: @entity880 :: ('MESH:D019344', 'Chemical') :: ['lactate']

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

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


abstract: Seventeen @entity1 with @entity5734 ( @entity5734 ) were treated with low doses of recombinant alpha interferon (IFN) for over 4 months. Marked improvement was observed in peripheral blood and bone marrow in 15 of 17 @entity1 . Comparison of pretreatment values and hemograms obtained after 4 months of treatment showed a marked decrease in circulating hairy cells (P less than .01), a decrease in the number of lymphocytes (P less than .01), a rise in the number of platelets (P less than .05), granulocytes (P less than .05), and monocytes (P less than .01), and a rise in the hemoglobin level (P less than .01). Transient reduction in the number of granulocytes was noted during the first month. Correction of @entity882 often appeared within 2 months and usually preceded improvement of @entity417 , monocytopenia, and @entity1398 . Bone marrow biopsy specimens were taken before treatment and 2, 4, and 7 months after its initiation. The volumes occupied by hairy cells, cells of the myeloid lines, and adipocytes were studied by stereological analysis of semithin sections. Decrease in the volume occupied by hairy cells was seen after 4 months of treatment (P less than .01), and the volume continued to decrease at the seventh month (P less than .05). Hairy cells were no longer detected on bone marrow biopsies of 4 of 17 @entity1 by the fourth month and in 3 of 8 additional @entity1 by the seventh month. A rise in the volume occupied by normal myeloid cells was visible by the second month of treatment (P less than .01). Nevertheless, the volume occupied by granulocytes remained lower than in the normal controls (P less than .01). After an initial increase during the first 2 months of treatment (P less than .01), the overall cellularity remained unchanged at 4 months and decreased significantly (P less than .05) at 7 months. Except for biopsies at 2 months, mean cellularity was below that of control biopsies (P less than .01).

title: Treatment of XXXX with recombinant alpha interferon: I. Quantitative study of bone marrow changes during the first months of treatment.

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

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

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

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

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


abstract: Fifty-seven @entity1 with a strong clinical suspicion of cervical @entity602 were studied with body coil magnetic resonance (MR) and conventional myelography or CT myelography. Eight @entity1 were believed to have normal studies with both modalities. There were six @entity1 with @entity1644 ; four with an intramedullary @entity5 ; one with an @entity2758 ; 19 with @entity4720 at multiple levels; eight with @entity4720 at a single level; four with extensive @entity309 ; four with extradural @entity5 ; two with @entity130 ; and one @entity1 with an @entity7181 . In this study, body coil MR was the superior examination for the evaluation of an intramedullary process. It was as diagnostic as myelography in one case of an extramedullary intradural lesion. In @entity1 with extradural disease, body coil MR was the superior study in 45%, equivalent to myelography in 37%, and, although still diagnostic, inferior to myelography in 17%. In 8% of the cases, body coil MR was at best equivocal, whereas myelography was diagnostic. It appears that in technically adequate studies, MR is at least equivalent to myelography in its ability to delineate disease. A superior MR study provides a better appraisal of the size and character of the spinal cord as well as the degree of both anterior and posterior defects on the subarachnoid space and neural structures. In addition, MR is as good as conventional myelography for the identification of extrinsic cervical @entity602 producing cervical @entity602 . Finally, an additional small group of 30 @entity1 were studied with a prototype surface coil to determine its advantages relative to body coil imaging. Each @entity1 had correlative myelography. As with body coil MR, imaging with the surface coil was believed to be more informative than conventional myelography in four @entity1 with intramedullary lesions. The remaining 26 @entity1 suffered from @entity4720 . Surface coil MR was believed to be more informative than myelography in six cases (23%), equivalent to myelography in 19 (73%), and less diagnostic than myelography in one (4%). The improved spatial resolution with the use of the surface coil was believed to increase the accuracy of MR.

title: Cervical XXXX : a comparison of magnetic resonance and myelography.

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

entities_list: @entity2758 :: ('MESH:D001165', 'Disease') :: ['arteriovenous malformation']

entities_list: @entity1644 :: ('MESH:D013595', 'Disease') :: ['syringomyelia']

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

entities_list: @entity602 :: ('MESH:D013118', 'Disease') :: ['myelopathy', 'cord lesions']

entities_list: @entity7181 :: ('MESH:D020802', 'Disease') :: ['epidural abscess']

entities_list: @entity4720 :: ('MESH:D055009', 'Disease') :: ['cervical spondylosis']

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

answer: @entity602 :: (MESH:D013118,Disease) :: ['myelopathy']


abstract: Two-cell ICR- @entity19 embryos were cultured to compare media used for @entity1 in vitro fertilization and embryo transfer (IVF-ET) programs. When delayed centrifuged (DC, a general method of serum preparation) adult @entity16557 ( @entity16557 ) was used as a medium supplement, Whitten's modified Krebs-Ringer- @entity3157 solution (m-KRB) was significantly better in both rate of development to blastocysts (D. R. to b1) and hatching rate (H.R.) than modified Ham's F-10 medium (m- @entity36312 ), irrespective of the commercial source of the @entity36312 powder. As for medium supplements when m-KRB was used as the medium base, immediately cooled and centrifuged (ICC, a new method of serum preparation) @entity16557 was significantly better in D.R. to bl. and H.R. than either DC- @entity16557 or DC-cord blood serum (CBS). There was no significant difference between DC- @entity16557 and DC-CBS. Moreover, ICC- @entity16557 gave a much higher H.R. than either bovine serum albumin (BSA) or human serum albumin (HSA), although D.R. to bl. was similar in all three. There was no significant difference between BSA and HSA. In clinical assessment of a @entity1 IVF-ET program, both the fertilization rate and the cleavage rate were higher in m-KRB containing ICC-patient's serum (PS) than in m- @entity36312 containing DC-PS, although the differences were not statistically significant.

title: Comparison of media used for XXXX in vitro fertilization and embryo transfer programs--a new method of serum preparation.

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

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


abstract: A total of 48 haemodialysed @entity1 were studied by radioimmunoassay for the serum concentrations of @entity6685 , @entity175 , @entity8243 , @entity2690 , prolactin, @entity3938 , T4, @entity3938 , TSH and @entity701 . Residual urines were measured for @entity268 and ultrafiltrates for iPTH and @entity8243 . The duration of the dialysis programme, the number of haemodialysis sessions per week, sex distribution, the dialysis alternatives (including haemofiltration, haemoperfusion) and successful kidney transplantations were correlated with the serum hormone levels. Significant increases in @entity461 , @entity8243 and prolactin values were demonstrated in the dialysed @entity1 . However, their @entity175 and @entity2690 concentrations decreased, parallel with the time elapsed since the start of the haemodialysis programme (HDP). The number of dialysis sessions per week was found to affect the hormone concentrations diversely. In the course of haemofiltration and haemoperfusion some of the hormone levels (e.g. @entity461 , @entity8243 ) decreased significantly. The @entity1 were in general euthyroid. One of them, on HDP for several years, developed clinical and laboratory signs indicative of @entity1378 . In a considerable proportion of the cases the results of the hormone studies (increased @entity461 , CT, @entity268 ) were consistent with @entity3528 . Kidney transplantation was followed by a decline of the serum prolactin, @entity6685 , @entity175 and @entity1369 levels.

title: Hormonal changes in haemodialysed and in kidney-transplanted XXXX .

entities_list: @entity175 :: ('MESH:D002116', 'Chemical') :: ['calcitonin']

entities_list: @entity1369 :: ('MESH:D000450', 'Chemical') :: ['aldosterone']

entities_list: @entity6685 :: ('MESH:D010281', 'Chemical') :: ['parathormone']

entities_list: @entity3528 :: ('MESH:D006962', 'Disease') :: ['secondary hyperparathyroidism']

entities_list: @entity1378 :: ('MESH:D006980', 'Disease') :: ['hyperthyroidism']

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

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


abstract: PURPOSE: To evaluate the influence of dose fractionation and other factors on the development of late complications in mandibular bone, muscle, and mucosa of the oral cavity after external beam radiation therapy for @entity189 . METHODS AND MATERIALS: A retrospective analysis was made of the results in 676 @entity1 treated with a spectrum of fractionation regimens in nine centers during the years 1976-1985. Only severe (Grades 3-4) late complications were analyzed. RESULTS: With more than 5 years follow-up, it was found that total dose was a factor for all three types of complications, but that in other respects, the radiobiology of late-(> 3 months) developing mucosal @entity1066 was different from that for mandibular @entity39 and @entity121 . Dose per fraction was a significant factor for bone and muscle (estimated alpha/beta values of 0.85 Gy and 3.1 Gy, respectively). By contrast, mucosa showed no influence on response from change in fraction size over the range of approximately 1.0-3.5 Gy. Complications in bone and muscle were not related to overall treatment duration, whereas there was a significant inverse relationship for @entity5932 . The rate of development of complications was fastest in mucosa and slowest in bone. The appearance of complications by 4 years after treatment was about 80% of those developing by 8 years in the mucosa, 66% in muscle, and about 50% in bone. The high alpha/beta ratio, inverse relationship with overall treatment duration, and @entity3137 suggests that they may develop as a consequence of earlier @entity3137 . As anticipated, adequate retrospective analysis of acute complications could not be made even when objective criteria such as @entity353 , unplanned delays in completing treatment, or hospitalization during treatment were the measures. Field size was a significant factor for mandible complications, but not for muscle or mucosa. CONCLUSION: The radiobiological characteristics of bone and muscle were those characteristic of other late-responding tissues, whereas late sequelae in mucosa had radiobiological parameters similar to those for acute responses. Field size was a significant factor for bone complications but not for others.

title: Late normal tissue sequelae from radiation therapy for XXXX : patterns of fractionation study of radiobiology.

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

entities_list: @entity353 :: ('MESH:D015431', 'Disease') :: ['weight loss']

entities_list: @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis']

entities_list: @entity1066 :: ('MESH:D014456', 'Disease') :: ['ulcerations']

entities_list: @entity5932 :: ('MESH:C565008', 'Disease') :: ['mucosa breakdown']

entities_list: @entity189 :: ('MESH:D002277', 'Disease') :: ['carcinoma of the tonsil']

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

entities_list: @entity3137 :: ('MESH:D009059', 'Disease') :: ['faster development of mucosal complications', 'mucosal injury']

answer: @entity189 :: (MESH:D002277,Disease) :: ['carcinoma of the tonsil']


abstract: PURPOSE: The feasibility and activity of an intensive chemoradiotherapeutic scheme for @entity1 with locally advanced @entity135 were tested in a single institution Phase II pilot study. METHODS AND MATERIALS: Between January 1990 and February 1992, 40 @entity1 were entered into this trial. The treatment protocol consisted of split hyperfractionated accelerated radiation therapy (SHART), 1.6 Gy per fraction given twice per day to a total dose of 64-67.2 Gy for a total of 6 weeks with a 2-week gap, and @entity900 (20 mg/sqm/Days 1 to 5, in continuous perfusion) concomitantly. RESULTS: All of the 40 @entity1 are evaluable for response and survival. @entity137 was significant, but tolerable. A complete @entity5 response to this treatment was achieved by 37 @entity1 (92.5%). With a minimal follow-up of 22 months (median 30 months) there have been 16 local relapses and 19 @entity1 have died, 2 without @entity5 . The projected 2- and 3-year overall survival rates are 64% (confidence interval (CI) 95%, 49-79%) and 47%, respectively. The 2-year local control probability has been 56% (CI 95%, 39-73%). CONCLUSION: This treatment obtains a high rate of complete responses with increased acute @entity137 but tolerable late effects. Preliminary results are encouraging for @entity25364 . A longer follow-up is needed to evaluate the impact of this treatment on @entity1 survival.

title: Split hyperfractionated accelerated radiation therapy and concomitant XXXX for locally advanced @entity135 : a preliminary report.

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

entities_list: @entity135 :: ('MESH:D006258', 'Disease') :: ['squamous cell head and neck cancers']

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

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

entities_list: @entity25364 :: ('MESH:D007822', 'Disease') :: ['laryngeal neoplasms']

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


abstract: PURPOSE: The feasibility and activity of an intensive chemoradiotherapeutic scheme for @entity1 with locally advanced @entity135 were tested in a single institution Phase II pilot study. METHODS AND MATERIALS: Between January 1990 and February 1992, 40 @entity1 were entered into this trial. The treatment protocol consisted of split hyperfractionated accelerated radiation therapy (SHART), 1.6 Gy per fraction given twice per day to a total dose of 64-67.2 Gy for a total of 6 weeks with a 2-week gap, and @entity900 (20 mg/sqm/Days 1 to 5, in continuous perfusion) concomitantly. RESULTS: All of the 40 @entity1 are evaluable for response and survival. @entity137 was significant, but tolerable. A complete @entity5 response to this treatment was achieved by 37 @entity1 (92.5%). With a minimal follow-up of 22 months (median 30 months) there have been 16 local relapses and 19 @entity1 have died, 2 without @entity5 . The projected 2- and 3-year overall survival rates are 64% (confidence interval (CI) 95%, 49-79%) and 47%, respectively. The 2-year local control probability has been 56% (CI 95%, 39-73%). CONCLUSION: This treatment obtains a high rate of complete responses with increased acute @entity137 but tolerable late effects. Preliminary results are encouraging for @entity25364 . A longer follow-up is needed to evaluate the impact of this treatment on @entity1 survival.

title: Split hyperfractionated accelerated radiation therapy and concomitant @entity900 for locally advanced XXXX : a preliminary report.

answer: @entity135 :: (MESH:D006258,Disease) :: ['head and neck carcinomas']


abstract: Our object was to describe demographic data from a population of adult asthmatics admitted to a regional tertiary medical center to identify risk factors for intubation. We performed a retrospective cohort study of all @entity565 admissions (International Classification of Diseases, Ninth Revision, Code 493.9) excluding cases with @entity1030 . This included all @entity1 with @entity565 20 years and above admitted to the University of California Davis Medical Center, Sacramento, from January 1, 1990 to June 30, 1993. A total of 375 @entity565 admissions were reviewed. There were 244 @entity1 (29 intubated) and 131 @entity1 (13 intubated) with a mean age of 40.7 (range 20-72) years. Of this group, 131 @entity1 were white, 140 black, 56 Hispanic, 42 Asian, and 6 American Indian. By National Heart, Lung, and Blood Institute Guidelines, there were 101 mild, 181 moderate, and 93 severe cases. Significant risk parameters identified for intubation were psychosocial problems [odds ratio (O.R.) 9.3; 95% confidence interval (C.I.) 6.8, 12.7], low socioeconomic group (O.R. 2.9; 95% C.I. 1.5, 5.8), little formal education (O.R. 5.4; 95% C.I. 2.8, 10.2), @entity566 (O.R. 11.7; 95% C.I. 5.7, 23.7), duration of @entity565 > or = 15 years (O.R. 2.6; 95% C.I. 1.3, 5.3), previous intubation (O.R. 14.0; 95% C.I. 7.6, 25.6), @entity1729 (O.R. 4.0; 95% C.I. 2.2, 7.5), hospital admission for @entity565 within the last year (O.R. 5.3; 95% C.I. 2.7, 10.4), emergency room visit within the last year (O.R. 8.8; 95% C.I. 3.9, 20.1), and @entity134 dependency (O.R. 5.5; 95% C.I. 3.0, 10.2).(ABSTRACT TRUNCATED AT 250 WORDS)

title: Risk factors for intubation of adult asthmatic XXXX .

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

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

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

entities_list: @entity1729 :: ('MESH:D012141', 'Disease') :: ['upper respiratory infection']

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

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


abstract: We describe a method for measuring the lean body mass (LBM) and total body @entity1386 (FAT) by dual photon absorptiometry ( @entity16771 ). A total body rectilinear scan was employed with a radiation source of 1 Ci 153Gd. The reliability of estimating the lean percent was assessed in vitro using limb phantoms consisting of ox muscle, lard, and @entity1 bone. The precision and accuracy in vitro of the lean percent determination were 1.5% and 1.9%, respectively. The accuracy error in vivo of measuring the total mass of soft tissues (TMST) was approximately 1.4%, thus yielding an overall accuracy error of the LBM of about 2.5%. The precision in vivo of the lean percent and the LBM in kg of duplicate measurements on five healthy subjects was 2.5% and 2.2%, respectively. Other estimates of the LBM and FAT, ie, the calculation according to Boddy et al6 and the skinfold thickness measurement (triceps and subscapular), were compared to the @entity16771 measurement in 100 healthy subjects. High correlations were found between the FAT or FAT% by @entity16771 versus (1) the FAT or FAT% calculated according to the formulae of Boddy et al, and (2) the skinfold thickness. The correlations between the FAT and FAT% by Boddy et al and the skinfold thickness were, however, moderate. The correlation between LBM by @entity16771 and LBM by Boddy et al was highly significant (r = 0.96, SEE = 4.4%). We conclude that LBM and FAT measurements using @entity16771 have precision and accuracy errors that are commensurate with a reliable estimation of the gross body composition.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Measurement of lean body mass and total body XXXX using dual photon absorptiometry.

answer: @entity1386 :: (MESH:D018205,Disease) :: ['fat']


abstract: UNASSIGNED: @entity263 is the second most frequently diagnosed @entity5 in the world. @entity66 can be effectively treated with radiation therapy or radical prostatectomy. However, advanced @entity263 is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced @entity263 . One potential target is the @entity5 stem cell (CSC). CSCs have been described in several solid @entity5 , including @entity263 , and contribute to therapeutic resistance and @entity5 recurrence. @entity2449 , a common oral @entity28943 used to treat @entity164 2 @entity6 , has been demonstrated to have anti-neoplastic effects. Specifically, @entity2449 targets CSCs in @entity0 , @entity788 , @entity463 and @entity694 . @entity2449 acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial @entity855 production. This forces @entity5 cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. @entity2449 could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional @entity5 therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in @entity5 propagation and therapeutic resistance and the role of @entity2449 as a potential prostate CSC sensitizer to current anticancer therapies. @entity263 and @entity4623 advance online publication, 28 July 2015; doi:10.1038/pcan.2015.35.

title: @entity2449 and XXXX stem cells: a novel therapeutic target.

entities_list: @entity788 :: ('MESH:D010190', 'Disease') :: ['pancreatic cancer']

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

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

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

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

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

entities_list: @entity28943 :: ('CHEBI:3095', 'Chemical') :: ['biguanide']

entities_list: @entity4623 :: ('MESH:D011469', 'Disease') :: ['Prostatic Disease']

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

entities_list: @entity463 :: ('MESH:D005909', 'Disease') :: ['glioblastoma']

entities_list: @entity2449 :: ('MESH:D008687', 'Chemical') :: ['Metformin', 'metformin']

answer: @entity263 :: (MESH:D011471,Disease) :: ['prostate cancer']


abstract: UNASSIGNED: @entity263 is the second most frequently diagnosed @entity5 in the world. @entity66 can be effectively treated with radiation therapy or radical prostatectomy. However, advanced @entity263 is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced @entity263 . One potential target is the @entity5 stem cell (CSC). CSCs have been described in several solid @entity5 , including @entity263 , and contribute to therapeutic resistance and @entity5 recurrence. @entity2449 , a common oral @entity28943 used to treat @entity164 2 @entity6 , has been demonstrated to have anti-neoplastic effects. Specifically, @entity2449 targets CSCs in @entity0 , @entity788 , @entity463 and @entity694 . @entity2449 acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial @entity855 production. This forces @entity5 cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. @entity2449 could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional @entity5 therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in @entity5 propagation and therapeutic resistance and the role of @entity2449 as a potential prostate CSC sensitizer to current anticancer therapies. @entity263 and @entity4623 advance online publication, 28 July 2015; doi:10.1038/pcan.2015.35.

title: XXXX and @entity263 stem cells: a novel therapeutic target.

answer: @entity2449 :: (MESH:D008687,Chemical) :: ['Metformin']


abstract: Marrow transplants were carried out between unrelated DLA-nonidentical @entity235 . Recipients were prepared for transplantation by 9.2 Gy single-dose @entity348 ( @entity348 ) administered at 7 cGy/min. All recipient @entity235 received marrow, 4 X 10(8) cells/kg, and no buffy coat cells. In addition to @entity348 , 19 @entity235 were given anti-class II monoclonal antibody (mAb) 7.2, either alone or combined with a second anti-class II mAb, HB10a, at doses of 0.2 or 0.4 mg/kg/day on days -5 to 0 or -1 to +3. Seven had hemopoietic engraftment. Ten @entity235 were given, in addition to @entity348 , @entity1499 ( @entity1500 ), 0.4 mg/kg/day on days 1, 3, 6, and 11 after grafting, and six had engraftment. Ten @entity235 were given a combination of mAb 7.2 pregrafting and @entity1500 after grafting, and 9 had evidence of engraftment. Among 7 @entity235 treated with the irrelevant mAb 31E6.4, only one had engraftment. Thus the administration of anti-class II mAb pregrafting and @entity1500 postgrafting had a beneficial effect in overcoming resistance to histoincompatible marrow grafts. Possibly this effect is more pronounced when both approaches are combined.

title: Engraftment of DLA-nonidentical bone marrow facilitated by recipient treatment with anti-class II monoclonal antibody and XXXX .

entities_list: @entity1499 :: ('MESH:D008727', 'Chemical') :: ['methotrexate']

entities_list: @entity348 :: ('MESH:C535338', 'Disease') :: ['total-body irradiation', 'TBI']

answer: @entity1499 :: (MESH:D008727,Chemical) :: ['methotrexate']


abstract: BACKGROUND: The nasal avian schistosome @entity21933 spends part of its intravertebrate period of life within the central nervous system. Migration of the parasites can be accompanied by @entity74 or @entity912 in natural definitive hosts ( @entity4186 ) and even in laboratory mammals. Cercariae are also able to penetrate @entity1 skin and induce @entity1909 . While the cellular and antibody responses against cercariae and migrating schistosomula have been investigated in @entity19 , little is known about immune reactions in birds. This study first describes the dynamics of antibody response in infected @entity4186 and identifies frequently recognized antigens that may serve as diagnostic markers of @entity281 by @entity21933 . METHODS: Groups of 35 @entity4186 and 10 @entity4186 were exposed to different doses of @entity21933 cercariae. Sera were collected at predefined time intervals and tested by ELISA for the presence of specific anti-cercarial IgY and IgM. Antigens recognized by the antibodies were identified on Western blots of cercariae and schistosomula. The applicability in immunodiagnostics was statistically evaluated by expression of specificity and sensitivity values for individual antigens. RESULTS: In ELISA, the levels of anti-cercarial IgM peaked on day 15 pi. Increased production of IgY associated with the later phases of @entity281 was observed in most individuals around 20 dpi and culminated 30 dpi. The time course of antibody response did not differ among experimental groups, variations were only observed in the levels of specific IgY which depended rather on the age of @entity4186 at the time of @entity281 than on the infectious dose. On Western blots, 40 cercarial and 7 schistosomular antigens were recognized by IgY from infected @entity4186 . Among them, 4 cercarial antigens of 50, 47, 32 and 19  kDa provided the most sensitive and specific reactions. CONCLUSIONS: Antigens of cercariae and schistosomula elicited distinct antibody response in @entity4186 , which correlated positively with the age of animals at the time of @entity281 . Several antigens originating in cercariae and fewer in schistosomula were recognized by IgY with diverse sensitivity and specificity; only a few seemed to be common to both stages. Four of them were considered as the most promising candidates for immunodiagnostics.

title: Antibody response of definitive hosts against antigens of two life stages of the neuropathogenic schistosome XXXX .

entities_list: @entity4186 :: ('8839', 'Species') :: ['mallards', 'domestic ducks', 'ducks']

entities_list: @entity21933 :: ('157069', 'Species') :: ['T. regenti', 'Trichobilharzia regenti']

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

entities_list: @entity74 :: ('MESH:D030342', 'Disease') :: ['neuromotor disorders']

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

entities_list: @entity912 :: ('MESH:D010243', 'Disease') :: ['paralysis']

answer: @entity21933 :: (157069,Species) :: ['Trichobilharzia regenti']


abstract: AIMS: Immunostaining of chromogranin identifies @entity344 cells. The detailed distribution and significance of chromogranin positive cells in @entity14 and in transitional mucosa remain unclear. The aim of this study was to clarify these aspects. METHODS: The distribution of chromogranin positive cells was studied by immunohistochemical methods in normal epithelium remote from @entity189 , in transitional mucosa, and in @entity189 of the colorectum. In selected cases northern or western blot analyses were performed. RESULTS: Chromogranin positive cells were seen in the lower third of the normal crypts and less frequently in transitional mucosa. Thirty five per cent (n = 38) of @entity14 showed immunohistochemically positive @entity189 cells in the @entity5 tissue. Northern and western blot analyses showed similar results. There was no difference in clinicopathological factors, including prognosis, between chromogranin positive cases of @entity14 (n = 38) and chromogranin negative cases (n = 70). CONCLUSIONS: Neuroendocrine cell differentiation is controlled in transitional mucosa and the presence of chromogranin positive cells in @entity189 tissue does not influence the @entity1 's prognosis.

title: Chromogranin positive cells in XXXX and transitional mucosa.

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

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

entities_list: @entity344 :: ('MESH:D005767', 'Disease') :: ['gastrointestinal mucosal endocrine']

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

answer: @entity14 :: (MESH:D015179,Disease) :: ['colorectal carcinoma']


abstract: OBJECTIVE: The purpose of this study was to evaluate large intracranial @entity439 by contrast-enhanced 3D MRI. MATERIALS AND METHODS: Eleven @entity1 , nine @entity1 and two @entity1 , were examined. The @entity439 involved the internal carotid artery in seven @entity1 , the middle cerebral artery in one, the basilar artery in two, and the posterior cerebral artery in one. Contrast-enhanced 3D MR images were obtained using FLASH (fast low angle shot) on a 1.5 T system. We obtained axial images first, then sagittal and coronal images by multiplanar reconstruction. Those images were reviewed for comparison with conventional and MR angiography. RESULTS: We could easily evaluate the true aneurysmal size, the intraaneurysmal constitution (patent lumen and intraluminal thrombus), and the detailed relationship of the @entity439 to the surrounding vascular and neural structures. Except for the cavernous internal carotid artery, we could identify the @entity439 by carefully observing axial, sagittal, and coronal images. In addition, the progression of intraaneurysmal @entity715 and the patency of the parent arterial lumen after the endovascular treatment were well appreciated. CONCLUSION: We consider that 3D MRI appears to be useful for evaluation of the large @entity438 .

title: Evaluation of large XXXX with three-dimensional MRI.

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

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

entities_list: @entity439 :: ('MESH:D000783', 'Disease') :: ['aneurysms', 'aneurysmal neck', 'aneurysm']

entities_list: @entity438 :: ('MESH:D002532', 'Disease') :: ['intracranial aneurysm']

answer: @entity438 :: (MESH:D002532,Disease) :: ['intracranial aneurysm']


abstract: A series of derivatives of @entity73165 ( @entity14217 ) was examined for interactions with @entity291 brain tubulin following the demonstration that many members of the class caused significant mitotic effects in intact animals, while others had activity against @entity19 @entity19 @entity1778 . In L1210 cells several @entity14217 derivatives caused a rise in the mitotic index which correlated well with the @entity137 of the drugs. Active @entity14217 derivatives markedly stimulated tubulin-dependent @entity3007 hydrolysis and inhibited tubulin polymerization or induced tubulin oligomer formation, depending on specific reaction conditions. These new agents, however, did not interfere with the binding to tubulin of radiolabeled @entity3812 , @entity5713 , @entity17204 , or @entity3007 . They thus appear to bind at a previously undescribed site on the tubulin molecule. Some @entity14217 derivatives have significant herbicidal activity, causing @entity952 and a rise in the mitotic index in seedling root tissues. Although the @entity14217 derivatives most toxic to plant tissues differ from those most active in inhibiting @entity291 brain tubulin polymerization, virtually all active compounds bear a @entity7575 substituent at position 4 of the @entity51385 ring. Most active derivatives also bear substituents of varying structure at position 2 of this ring, but no clear structure-function pattern is apparent at this position. The @entity15060 rings in the most active herbicidal @entity14217 derivatives either are unsubstituted or bear @entity2862 atoms. Derivatives with @entity3878 substituents have no detectable herbicidal activity. In contrast, interactions with @entity291 brain tubulin are substantially enhanced if the @entity15060 rings bear @entity3878 substituents.

title: Derivatives of XXXX : synthetic antimitotic agents which interact with plant and mammalian tubulin at a new drug-binding site.

entities_list: @entity3007 :: ('MESH:D006160', 'Chemical') :: ['guanosine triphosphate']

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

entities_list: @entity73165 :: ('MESH:C068053', 'Chemical') :: ['5,6-diphenylpyridazin-3-one']

entities_list: @entity3878 :: ('MESH:D002713', 'Chemical') :: ['chlorine']

entities_list: @entity51385 :: ('CHEBI:26414', 'Chemical') :: ['pyridazinone']

entities_list: @entity7575 :: ('CHEBI:18379', 'Chemical') :: ['nitrile']

entities_list: @entity2862 :: ('MESH:D005461', 'Chemical') :: ['fluorine']

entities_list: @entity952 :: ('MESH:D019958', 'Disease') :: ['mitotic disruption']

entities_list: @entity3812 :: ('MESH:D003078', 'Chemical') :: ['colchicine']

entities_list: @entity5713 :: ('MESH:D014747', 'Chemical') :: ['vinblastine']

entities_list: @entity17204 :: ('MESH:D008453', 'Chemical') :: ['maytansine']

answer: @entity73165 :: (MESH:C068053,Chemical) :: ['5,6-diphenylpyridazin-3-one']


abstract: Alterations in plasma lipoprotein lipid and apoprotein accompanying the @entity407 of @entity35 bearing @entity7283 7288C were characterized. In @entity5 -bearing animals all plasma lipid classes except @entity14839 (CE) were elevated, particularly free @entity165 (FC) and @entity412 (TG), which increased by 57 and 63%, respectively. Fasting only partially reduced the @entity5 -induced @entity407 and had no effect on the ratios of FC/CE and TG/CE. Analysis of plasma lipoproteins revealed an elevation of VLDL, IDL, and LDL in host @entity35 , with more than a 2-fold increase in both lipid and protein of VLDL. In contrast, the three high density fractions, @entity17120 , HDL3, and d greater than 1.21 g/ml, were reduced. The inverse changes in concentration of host lipoproteins of lower versus higher density indicate a defective catabolism of TG-rich lipoprotein. This possibility is supported by the analysis of apolipoprotein. The percentage of total apoprotein contributed by apo C-I and C-II was reduced in all host fractions except @entity17120 , while the C-IIIs remained unchanged except for a small decrease in C-III-3 of host VLDL and a slight increase in the combined C-IIIs of @entity17120 . These changes were reflected in the decreased C-I+C-II/C-III ratios of all host lipoprotein fractions. @entity12217 levels remained similar to control values except for a significant decrease in @entity17120 . Host VLDL showed increased @entity12216 and A-I content, while A-IV was decreased in @entity17120 . Changes in apo B profiles were also observed.

title: Characterization of alterations in plasma lipoprotein lipid and apoprotein profiles accompanying hepatoma-induced XXXX in @entity35 .

entities_list: @entity407 :: ('MESH:D006949', 'Disease') :: ['hyperlipidemia']

entities_list: @entity14839 :: ('CHEBI:17002', 'Chemical') :: ['cholesterol ester']

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

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

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

answer: @entity407 :: (MESH:D006949,Disease) :: ['hyperlipidemia']


abstract: Alterations in plasma lipoprotein lipid and apoprotein accompanying the @entity407 of @entity35 bearing @entity7283 7288C were characterized. In @entity5 -bearing animals all plasma lipid classes except @entity14839 (CE) were elevated, particularly free @entity165 (FC) and @entity412 (TG), which increased by 57 and 63%, respectively. Fasting only partially reduced the @entity5 -induced @entity407 and had no effect on the ratios of FC/CE and TG/CE. Analysis of plasma lipoproteins revealed an elevation of VLDL, IDL, and LDL in host @entity35 , with more than a 2-fold increase in both lipid and protein of VLDL. In contrast, the three high density fractions, @entity17120 , HDL3, and d greater than 1.21 g/ml, were reduced. The inverse changes in concentration of host lipoproteins of lower versus higher density indicate a defective catabolism of TG-rich lipoprotein. This possibility is supported by the analysis of apolipoprotein. The percentage of total apoprotein contributed by apo C-I and C-II was reduced in all host fractions except @entity17120 , while the C-IIIs remained unchanged except for a small decrease in C-III-3 of host VLDL and a slight increase in the combined C-IIIs of @entity17120 . These changes were reflected in the decreased C-I+C-II/C-III ratios of all host lipoprotein fractions. @entity12217 levels remained similar to control values except for a significant decrease in @entity17120 . Host VLDL showed increased @entity12216 and A-I content, while A-IV was decreased in @entity17120 . Changes in apo B profiles were also observed.

title: Characterization of alterations in plasma lipoprotein lipid and apoprotein profiles accompanying hepatoma-induced @entity407 in XXXX .

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


abstract: BACKGROUND: Expression of the @entity6824 ( @entity6824 ) gene is elevated in most @entity2967 . This observation has led to the discovery and clinical development of therapy targeting the @entity6823 ( @entity6823 ). METHODS: Using x-ray co-crystallography to guide our drug-discovery research, we generated a potent, selective @entity6823 inhibitor, @entity6827 , that traps the kinase in the autoinhibited conformation. We then conducted a multicenter, phase 1 trial in two parts to analyze this compound. In the first part, we evaluated escalations in the dose of @entity6827 that was administered orally in @entity1 with solid @entity5 (dose-escalation study). In the second part, we evaluated @entity6827 at the chosen phase 2 dose in an extension cohort of @entity1 with @entity2967 (extension study). Pharmacokinetic and @entity5 responses in the enrolled @entity1 were assessed, and @entity6824 in situ hybridization was performed to confirm the mechanism of action of @entity6827 and that the pattern of @entity6824 expression was consistent with the pathological features of @entity2967 . RESULTS: A total of 41 @entity1 were enrolled in the dose-escalation study, and an additional 23 @entity1 were enrolled in the extension study. The chosen phase 2 dose of @entity6827 was 1000 mg per day. In the extension study, 12 @entity1 with @entity2967 had a partial response and 7 @entity1 had stable disease. Responses usually occurred within the first 4 months of treatment, and the median duration of response exceeded 8 months. The most common adverse events included fatigue, change in hair color, @entity390 , @entity2342 , and periorbital @entity4 ; adverse events rarely led to discontinuation of treatment. CONCLUSIONS: Treatment of @entity2967 with @entity6827 resulted in a prolonged regression in @entity5 volume in most @entity1 . (Funded by Plexxikon; ClinicalTrials.gov number, NCT01004861.).

title: Structure-Guided Blockade of XXXX Kinase in @entity2967 .

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

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

entities_list: @entity2967 :: ('MESH:D005870', 'Disease') :: ['tenosynovial giant-cell tumors', 'tenosynovial giant-cell tumor']

entities_list: @entity6824 :: ('1435', 'Gene') :: ['CSF1', 'colony-stimulating factor 1']

entities_list: @entity2342 :: ('MESH:D004408', 'Disease') :: ['dysgeusia']

answer: @entity6823 :: (1436,Gene) :: ['CSF1R']


abstract: BACKGROUND: Expression of the @entity6824 ( @entity6824 ) gene is elevated in most @entity2967 . This observation has led to the discovery and clinical development of therapy targeting the @entity6823 ( @entity6823 ). METHODS: Using x-ray co-crystallography to guide our drug-discovery research, we generated a potent, selective @entity6823 inhibitor, @entity6827 , that traps the kinase in the autoinhibited conformation. We then conducted a multicenter, phase 1 trial in two parts to analyze this compound. In the first part, we evaluated escalations in the dose of @entity6827 that was administered orally in @entity1 with solid @entity5 (dose-escalation study). In the second part, we evaluated @entity6827 at the chosen phase 2 dose in an extension cohort of @entity1 with @entity2967 (extension study). Pharmacokinetic and @entity5 responses in the enrolled @entity1 were assessed, and @entity6824 in situ hybridization was performed to confirm the mechanism of action of @entity6827 and that the pattern of @entity6824 expression was consistent with the pathological features of @entity2967 . RESULTS: A total of 41 @entity1 were enrolled in the dose-escalation study, and an additional 23 @entity1 were enrolled in the extension study. The chosen phase 2 dose of @entity6827 was 1000 mg per day. In the extension study, 12 @entity1 with @entity2967 had a partial response and 7 @entity1 had stable disease. Responses usually occurred within the first 4 months of treatment, and the median duration of response exceeded 8 months. The most common adverse events included fatigue, change in hair color, @entity390 , @entity2342 , and periorbital @entity4 ; adverse events rarely led to discontinuation of treatment. CONCLUSIONS: Treatment of @entity2967 with @entity6827 resulted in a prolonged regression in @entity5 volume in most @entity1 . (Funded by Plexxikon; ClinicalTrials.gov number, NCT01004861.).

title: Structure-Guided Blockade of @entity6823 Kinase in XXXX .

answer: @entity2967 :: (MESH:D005870,Disease) :: ['Tenosynovial Giant-Cell Tumor']


abstract: OBJECTIVES: We attempted to determine whether a family history of severe @entity65 in @entity1 with the @entity1614 is associated with @entity384 or decreased survival, or both. BACKGROUND: The prognostic importance of a family history of severe @entity65 in @entity1 with the @entity1614 has been incompletely examined. We hypothesized that such a family history would correlate with @entity384 and would be associated with decreased survival. METHODS: One hundred eight affected @entity1 and 48 unaffected family members from 33 multigenerational families with the @entity1614 underwent echocardiographic measurement of the aortic root, arch and mid-abdominal aorta. Date of birth and age at @entity204 ascertained from family pedigrees were used to perform life table analysis and estimate survival. RESULTS: Aortic root and arch diameters were significantly greater in @entity1 with a family history of severe @entity65 than in @entity1 without such a family history. Of subjects in the highest quartile for aortic size, > 80% had such a family history in contrast to < 10% of those in the lowest quartile (chi-square 57.37, p < 0.00001). Mean age at @entity204 and cumulative probability of survival were significantly lower in @entity1 with such a family history. CONCLUSIONS: Among @entity1 with the @entity1614 , @entity384 is greater and life expectancy shorter in those with a family history of severe cardiovascular manifestations. These data suggest that such a family history is an important risk factor for cardiovascular events in @entity1 with the @entity1614 .

title: Family history of severe @entity65 in XXXX is associated with increased aortic diameter and decreased survival.

entities_list: @entity384 :: ('MESH:D002311', 'Disease') :: ['aortic dilation', 'increased aortic dilation']

entities_list: @entity1614 :: ('MESH:D008382', 'Disease') :: ['Marfan syndrome']

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

answer: @entity1614 :: (MESH:D008382,Disease) :: ['Marfan syndrome']


abstract: OBJECTIVES: We attempted to determine whether a family history of severe @entity65 in @entity1 with the @entity1614 is associated with @entity384 or decreased survival, or both. BACKGROUND: The prognostic importance of a family history of severe @entity65 in @entity1 with the @entity1614 has been incompletely examined. We hypothesized that such a family history would correlate with @entity384 and would be associated with decreased survival. METHODS: One hundred eight affected @entity1 and 48 unaffected family members from 33 multigenerational families with the @entity1614 underwent echocardiographic measurement of the aortic root, arch and mid-abdominal aorta. Date of birth and age at @entity204 ascertained from family pedigrees were used to perform life table analysis and estimate survival. RESULTS: Aortic root and arch diameters were significantly greater in @entity1 with a family history of severe @entity65 than in @entity1 without such a family history. Of subjects in the highest quartile for aortic size, > 80% had such a family history in contrast to < 10% of those in the lowest quartile (chi-square 57.37, p < 0.00001). Mean age at @entity204 and cumulative probability of survival were significantly lower in @entity1 with such a family history. CONCLUSIONS: Among @entity1 with the @entity1614 , @entity384 is greater and life expectancy shorter in those with a family history of severe cardiovascular manifestations. These data suggest that such a family history is an important risk factor for cardiovascular events in @entity1 with the @entity1614 .

title: Family history of severe XXXX in @entity1614 is associated with increased aortic diameter and decreased survival.

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


abstract: BACKGROUND: In the United Arab Emirates the sting of the Pachycondyla sennaarensis ant (PSA) causes @entity56 in certain @entity1 . It is a common problem and is becoming a public health hazard. Up to now the diagnosis has been based only on the history, because the mechanism of the reaction was not yet established. OBJECTIVE: The aim of our study was to prepare an allergenic extract that would be used for skin tests and to prepare a reagent for specific IgE titration. Results of both skin tests and specific IgE were to be compared with the clinical history. METHODS: We studied 31 @entity1 with anaphylactic reactions and performed clinical examinations, skin tests, and specific IgE antibody titrations. A control group of 22 subjects were also studied. RESULTS: In 30 of 31 @entity1 (97%) findings of PSA skin tests and/or specific IgE were positive. In the control groups PSA skin test results were negative in 86% and negative for specific IgE in 68%. CONCLUSION: The study shows that the mechanism of the reaction to the sting of the PSA is a type I @entity10284 and that the diagnosis can now be confirmed by skin tests and specific IgE determination.

title: Systemic reactions to the Samsum ant: an XXXX .

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

entities_list: @entity10284 :: ('MESH:D006969', 'Disease') :: ['IgE-mediated hypersensitivity']

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

answer: @entity10284 :: (MESH:D006969,Disease) :: ['IgE-mediated hypersensitivity']


abstract: The aim of this study was to test effects of preventive regimes using @entity1388 and @entity1216 to prevent @entity2520 in 34 @entity1 with overdentures. The @entity1 , who were treated with immediate overdentures, were distributed at random into three experimental groups. In these groups, different gels--a placebo, a @entity1388 , and a @entity1216 - @entity1388 gel--were tested by daily application. @entity527 samples from selected surfaces of two abutment teeth were taken at one week, and at one, three, and six months after initial insertion of the overdenture. The placebo and @entity1388 gel influenced neither total CFU nor @entity885 and A. viscosus/naeslundii counts. In the placebo group, but not in the @entity1388 group, @entity6586 levels increased significantly, indicating the caries risk involved in overdentures. The use of @entity1216 - @entity1388 gel resulted in a long-term suppression of total CFU. Further, @entity6586 was found to be selectively suppressed to below detection level. A. viscosus/naeslundii was initially strongly suppressed, but after three months a partial return of the population was noticed. @entity885 was relatively insensitive to the @entity1216 - @entity1388 gel. It is concluded that a daily application of a @entity1216 - @entity1388 gel is effective against plaque formation and @entity6586 on abutment teeth in overdentures.

title: Microbial aspects of preventive regimes in XXXX with overdentures.

entities_list: @entity1216 :: ('MESH:D002710', 'Chemical') :: ['chlorhexidine']

entities_list: @entity527 :: ('MESH:D058225', 'Disease') :: ['Supragingival plaque']

entities_list: @entity2520 :: ('MESH:D010510', 'Disease') :: ['caries and periodontal diseases']

entities_list: @entity1388 :: ('MESH:D005459', 'Chemical') :: ['fluoride']

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


abstract: Mitogen-activated protein kinase (MAPK) cascades are critical signaling modules that mediate the transduction of extracellular stimuli into intracellular response. A relatively large number of MAPKKKs have been identified in a variety of plant genomes but only a few of them have been studied for their biological function. In the present study, we identified an @entity958 Raf-like MAPKKK gene Raf43 and studied its function in biotic and abiotic stress response using a T-DNA insertion mutant raf43-1 and two Raf43-overexpressing lines Raf43-OE#1 and Raf43-OE#13. Expression of Raf43 was induced by multiple abiotic and biotic stresses including treatments with drought, @entity2656 and oxidative stress or defense signaling molecule @entity3785 and @entity281 with necrotrophic fungal pathogen @entity14261 . Seed germination and seedling root growth of raf43-1 were significantly inhibited on MS medium containing @entity2656 , @entity4202 , @entity5568 or @entity6453 (MV) while seed germination and seedling root growth of the Raf43-OE#1 and Raf43-OE#13 lines was similar to wild type Col-0 under the above stress conditions. Soil-grown raf43-1 plants exhibited reduced tolerance to MV, drought and salt stress. @entity2271 inhibited significantly seed germination and seedling root growth of the raf43-1 line but had no effect on the two Raf43-overexpressing lines. Expression of stress-responsive @entity52039 and @entity44547 genes was significantly down-regulated in raf43-1 plants. However, the raf43-1 and Raf43-overexpressing plants showed similar disease phenotype to the wild type plants after @entity281 with @entity14261 or @entity14348 . Our results demonstrate that Raf43, encoding for a Raf-like MAPKKK, is required for tolerance to multiple abiotic stresses in @entity958 .

title: XXXX Raf-Like Mitogen-Activated Protein Kinase Kinase Kinase Gene Raf43 Is Required for Tolerance to Multiple Abiotic Stresses.

entities_list: @entity2656 :: ('MESH:D008353', 'Chemical') :: ['mannitol']

entities_list: @entity3785 :: ('MESH:D020156', 'Chemical') :: ['salicylic acid']

entities_list: @entity6453 :: ('MESH:D010269', 'Chemical') :: ['methyl viologen']

entities_list: @entity2271 :: ('MESH:D000040', 'Chemical') :: ['Abscisic acid']

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

entities_list: @entity14348 :: ('223283', 'Species') :: ['Pseudomonas syringae pv. tomato DC3000']

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

entities_list: @entity14261 :: ('40559', 'Species') :: ['B. cinerea', 'Botrytis cinerea']

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


abstract: 1. Electrophysiological recordings were made from neurones in the submucous plexus of the @entity840 small intestine, and these neurones were classified according to their synaptic inputs. 2. The neurones from which recording were made were filled during the recording period with the fluorescent dye, Lucifer Yellow, so they could be re-identified after processing for immunohistochemical localization of vasoactive intestinal peptide ( @entity6891 ). 3. The presence or absence of @entity6891 -like immunoreactivity was determined for a total of 130 neurones whose synaptic inputs had been fully characterized and eighty-two were found to be @entity6891 reactive. After the @entity6891 reactivity had been assessed, the preparations were reprocessed to reveal immunoreactivity for @entity6892 ( @entity6892 ) and a further twenty-three neurones (none of which were reactive for @entity6891 ) were found to be reactive for this peptide. Of the remaining twenty-five neurones, nineteen were not reactive for either @entity6891 or @entity6892 and six could not be re-identified after reprocessing. 4. Electrical stimulation of internodal strands evoked excitatory synaptic potentials lasting 20-30 ms (fast responses) in all but one of the 130 neurones studied. 5. Almost all the @entity6891 -reactive neurones (seventy-eight of eighty-two cells) exhibited inhibitory synaptic potentials, ranging in amplitude from 2 to 30 mV and lasting 150-1500 ms, but few of the @entity6891 -negative neurones had such responses (six of forty-eight cells). No inhibitory synaptic potentials could be evoked in any of the @entity6892 -reactive neurones. 6. Most @entity6891 -reactive neurones (sixty-nine) had a slow excitatory synaptic potential which could be evoked by a single stimulus, lasted 5-20 s and was associated with an increase in input resistance. Only one @entity6892 -reactive neurone had a slow excitatory potential, but such potentials were seen in nine of the nineteen @entity6891 -negative, @entity6892 -negative neurones. 7. In nine of the twenty-three @entity6892 -reactive neurones a single stimulus evoked an excitatory synaptic potential (intermediate excitatory synaptic potential) lasting 500-1500 ms and associated with a fall in the input resistance. None of the @entity6891 -negative, @entity6892 -negative neurones exhibited the intermediate excitatory potentials but it was not possible to determine whether such potentials could be evoked in @entity6891 -reactive neurones because the inhibitory synaptic potentials would obscure such events. 8. It is concluded that neurochemically distinct populations of submucous neurones can be distinguished physiologically on the basis of the differing combinations of types of synaptic input they receive.

title: Synaptic inputs to immunohistochemically identified neurones in the submucous plexus of the XXXX small intestine.

answer: @entity840 :: (10141,Species) :: ['guinea-pig']