abstract: UNASSIGNED: @entity2 ( @entity4 ) is widely used to treat chronic inflammatory diseases in the clinic. Increasingly, there is more attention being paid to the side effect of @entity4 . In this study, we investigated the involvement and mechanism of @entity4 exposure in accelerating mineralization during long bone formation. We first determined that @entity4 exposure could accelerate long bone mineralization in  vivo, but there was no apparent difference between control and @entity4 -treated in the phalanges model in  vitro. Next, we established that @entity4 exposure promoted angiogenesis in the @entity3 yolk sac membrane model. In addition, it increased @entity0 umbilical vein endothelial cell proliferation and migration in culture. We found that @entity4 could enhance angiogenesis when phalanges were cultured on @entity3 chorioallantoic membrane and correspondingly increased the expression of angiogenesis-related genes in the phalanges. Furthermore, we also revealed that @entity4 exposure reduced the number of osteoblasts and simultaneously increased the number of osteocytes in ex vivo-cultured phalanges. @entity5 and @entity6 expressions were up-regulated by @entity4 exposure, indicating that @entity4 exposure accelerated the terminal differentiation of osteoblasts. Lastly, we demonstrated that @entity1 cells cultured in the presence of @entity4 accelerated their mineralization. In summary, we have shown that the ability of @entity4 to initiate angiogenesis is the mechanism that allows it to accelerate mineralization during long bone formation.

title: XXXX Exposure Accelerates Endochondral Ossification of @entity3 Embryos Via Angiogenesis.

answer: @entity2


abstract: UNASSIGNED: @entity2 ( @entity4 ) is widely used to treat chronic inflammatory diseases in the clinic. Increasingly, there is more attention being paid to the side effect of @entity4 . In this study, we investigated the involvement and mechanism of @entity4 exposure in accelerating mineralization during long bone formation. We first determined that @entity4 exposure could accelerate long bone mineralization in  vivo, but there was no apparent difference between control and @entity4 -treated in the phalanges model in  vitro. Next, we established that @entity4 exposure promoted angiogenesis in the @entity3 yolk sac membrane model. In addition, it increased @entity0 umbilical vein endothelial cell proliferation and migration in culture. We found that @entity4 could enhance angiogenesis when phalanges were cultured on @entity3 chorioallantoic membrane and correspondingly increased the expression of angiogenesis-related genes in the phalanges. Furthermore, we also revealed that @entity4 exposure reduced the number of osteoblasts and simultaneously increased the number of osteocytes in ex vivo-cultured phalanges. @entity5 and @entity6 expressions were up-regulated by @entity4 exposure, indicating that @entity4 exposure accelerated the terminal differentiation of osteoblasts. Lastly, we demonstrated that @entity1 cells cultured in the presence of @entity4 accelerated their mineralization. In summary, we have shown that the ability of @entity4 to initiate angiogenesis is the mechanism that allows it to accelerate mineralization during long bone formation.

title: @entity2 Exposure Accelerates Endochondral Ossification of XXXX Embryos Via Angiogenesis.

answer: @entity3


abstract: We infused glucagon into normal @entity0 while preventing changes in plasma @entity1 and @entity4 . @entity4 (0.45 mU . @entity2 . kg-1) were infused for 90 min, while euglycemia was maintained by a variable @entity1 infusion. Subsequently, glucagon (6 ng . @entity2 . kg-1) was added, and changes in plasma @entity1 were avoided by appropriately reducing the @entity1 infusion. With @entity4 alone, @entity1 production (GP) fell to zero. When hyperglucagonemia (530 +/- 32 pg/ml) was superimposed, GP rose promptly and then slowly declined. However, between 180 and 240 min, GP remained elevated (1.72 +/- 0.30 mg . @entity2 . kg-1) as compared to an @entity4 control study (0.03 +/- 0.20, P less than 0.025). When @entity6 (+25 mg/100 ml) was induced between 180 and 240 min, glucagon-stimulated GP was completely suppressed. To determine whether this effect was mediated by @entity6 per se or @entity1 -induced @entity5 , between 180 and 240 min we increased either a) the @entity4 infusion (by 0.25 mU . @entity2 . kg-1) while maintaining euglycemia or b) plasma @entity1 (+25 mg/100 ml) while blocking @entity4 release with @entity3 . When the @entity4 was increased, GP declined by 68 +/- 13% (P less than 0.02). When plasma @entity1 alone was raised, GP fell from 1.44 +/- 0.09 to 0.07 +/- 0.16 mg . @entity2 . kg-1 (less than 0.002). In conclusion, the hepatic response to sustained hyperglucagonemia is more persistent if changes in plasma @entity1 are prevented, and its transient nature is in part explained by a feedback adjustment to glucagon-induced @entity6 and @entity5 .

title: Transient hepatic response to glucagon in @entity0 : role of @entity4 and XXXX .

answer: @entity6


abstract: We infused glucagon into normal @entity0 while preventing changes in plasma @entity1 and @entity4 . @entity4 (0.45 mU . @entity2 . kg-1) were infused for 90 min, while euglycemia was maintained by a variable @entity1 infusion. Subsequently, glucagon (6 ng . @entity2 . kg-1) was added, and changes in plasma @entity1 were avoided by appropriately reducing the @entity1 infusion. With @entity4 alone, @entity1 production (GP) fell to zero. When hyperglucagonemia (530 +/- 32 pg/ml) was superimposed, GP rose promptly and then slowly declined. However, between 180 and 240 min, GP remained elevated (1.72 +/- 0.30 mg . @entity2 . kg-1) as compared to an @entity4 control study (0.03 +/- 0.20, P less than 0.025). When @entity6 (+25 mg/100 ml) was induced between 180 and 240 min, glucagon-stimulated GP was completely suppressed. To determine whether this effect was mediated by @entity6 per se or @entity1 -induced @entity5 , between 180 and 240 min we increased either a) the @entity4 infusion (by 0.25 mU . @entity2 . kg-1) while maintaining euglycemia or b) plasma @entity1 (+25 mg/100 ml) while blocking @entity4 release with @entity3 . When the @entity4 was increased, GP declined by 68 +/- 13% (P less than 0.02). When plasma @entity1 alone was raised, GP fell from 1.44 +/- 0.09 to 0.07 +/- 0.16 mg . @entity2 . kg-1 (less than 0.002). In conclusion, the hepatic response to sustained hyperglucagonemia is more persistent if changes in plasma @entity1 are prevented, and its transient nature is in part explained by a feedback adjustment to glucagon-induced @entity6 and @entity5 .

title: Transient hepatic response to glucagon in @entity0 : role of XXXX and @entity6 .

answer: @entity4


abstract: We infused glucagon into normal @entity0 while preventing changes in plasma @entity1 and @entity4 . @entity4 (0.45 mU . @entity2 . kg-1) were infused for 90 min, while euglycemia was maintained by a variable @entity1 infusion. Subsequently, glucagon (6 ng . @entity2 . kg-1) was added, and changes in plasma @entity1 were avoided by appropriately reducing the @entity1 infusion. With @entity4 alone, @entity1 production (GP) fell to zero. When hyperglucagonemia (530 +/- 32 pg/ml) was superimposed, GP rose promptly and then slowly declined. However, between 180 and 240 min, GP remained elevated (1.72 +/- 0.30 mg . @entity2 . kg-1) as compared to an @entity4 control study (0.03 +/- 0.20, P less than 0.025). When @entity6 (+25 mg/100 ml) was induced between 180 and 240 min, glucagon-stimulated GP was completely suppressed. To determine whether this effect was mediated by @entity6 per se or @entity1 -induced @entity5 , between 180 and 240 min we increased either a) the @entity4 infusion (by 0.25 mU . @entity2 . kg-1) while maintaining euglycemia or b) plasma @entity1 (+25 mg/100 ml) while blocking @entity4 release with @entity3 . When the @entity4 was increased, GP declined by 68 +/- 13% (P less than 0.02). When plasma @entity1 alone was raised, GP fell from 1.44 +/- 0.09 to 0.07 +/- 0.16 mg . @entity2 . kg-1 (less than 0.002). In conclusion, the hepatic response to sustained hyperglucagonemia is more persistent if changes in plasma @entity1 are prevented, and its transient nature is in part explained by a feedback adjustment to glucagon-induced @entity6 and @entity5 .

title: Transient hepatic response to glucagon in XXXX : role of @entity4 and @entity6 .

answer: @entity0


abstract: PURPOSE: This study evaluated the functional and oncological outcomes of @entity5 ( @entity5 ) in comparison with @entity2 ( @entity2 ) for upper-third @entity4 ( @entity4 ). MATERIALS AND METHODS: The medical records of upper-third @entity4 @entity0 who had undergone @entity5 (n=192) or @entity2 (n=157) were reviewed. The @entity5 group was further subdivided into @entity0 who had undergone conventional open @entity5 (cPG; n=157) or modified laparoscopy-assisted @entity5 (mLAPG; n=35). @entity0 who had undergone mLAPG had a longer portion of their intra-abdominal esophagus preserved than @entity0 who had undergone cPG. Surgical morbidity, recurrence, long-term nutritional status, and the incidence of @entity3 were compared between the groups. RESULTS: The rate of @entity1 was significantly lower for @entity5 than @entity2 (16.7% vs. 31.2%), but the five-year overall survival rate was comparable between the two groups (99.3% vs. 96.3%). Postoperative levels of hemoglobin and albumin were significantly higher for @entity0 who had undergone @entity5 . However, the incidence of @entity3 was higher for @entity5 than for @entity2 (37.4% vs. 3.7%; P<0.001). mLAPG was related to a lower incidence of @entity3 after @entity5 (P<0.001). CONCLUSIONS: Compared to @entity2 , @entity5 showed an advantage in terms of postoperative morbidity and nutrition, and there was a comparable prognosis between the two procedures. Preserving the intra-abdominal esophagus may lower the incidence of @entity3 associated with @entity5 .

title: Clinical Outcome of Modified Laparoscopy-Assisted Proximal Gastrectomy Compared to Conventional Proximal Gastrectomy or Total Gastrectomy for Upper-Third Early XXXX with Special References to Postoperative @entity3 .

answer: @entity4


abstract: PURPOSE: This study evaluated the functional and oncological outcomes of @entity5 ( @entity5 ) in comparison with @entity2 ( @entity2 ) for upper-third @entity4 ( @entity4 ). MATERIALS AND METHODS: The medical records of upper-third @entity4 @entity0 who had undergone @entity5 (n=192) or @entity2 (n=157) were reviewed. The @entity5 group was further subdivided into @entity0 who had undergone conventional open @entity5 (cPG; n=157) or modified laparoscopy-assisted @entity5 (mLAPG; n=35). @entity0 who had undergone mLAPG had a longer portion of their intra-abdominal esophagus preserved than @entity0 who had undergone cPG. Surgical morbidity, recurrence, long-term nutritional status, and the incidence of @entity3 were compared between the groups. RESULTS: The rate of @entity1 was significantly lower for @entity5 than @entity2 (16.7% vs. 31.2%), but the five-year overall survival rate was comparable between the two groups (99.3% vs. 96.3%). Postoperative levels of hemoglobin and albumin were significantly higher for @entity0 who had undergone @entity5 . However, the incidence of @entity3 was higher for @entity5 than for @entity2 (37.4% vs. 3.7%; P<0.001). mLAPG was related to a lower incidence of @entity3 after @entity5 (P<0.001). CONCLUSIONS: Compared to @entity2 , @entity5 showed an advantage in terms of postoperative morbidity and nutrition, and there was a comparable prognosis between the two procedures. Preserving the intra-abdominal esophagus may lower the incidence of @entity3 associated with @entity5 .

title: Clinical Outcome of Modified Laparoscopy-Assisted Proximal Gastrectomy Compared to Conventional Proximal Gastrectomy or Total Gastrectomy for Upper-Third Early @entity4 with Special References to Postoperative XXXX .

answer: @entity3


abstract: The definition of @entity9 -related @entity2 (BRONJ) was recently broadened and it is now known as medication-related @entity2 (MRONJ). To date, the management of MRONJ is controversial. Conservative treatment is recommended, but it is difficult to successfully treat stage 3 MRONJ. Administration of @entity10 for the MRONJ treatment has only been documented in independent case reports and there are few reports on @entity0 with MRONJ treated with @entity10 . An 81-year-old @entity0 was referred in May 2014 for treatment of an unhealed tooth extraction wound in the mandible. He took @entity11 (1mg/d orally) for 2 years because of @entity4 cure. On clinical examination, soft tissue @entity1 in the left mandibular first molar region extended to the inferior border of the mandible with extraoral @entity6 . Computed tomography (CT) revealed @entity8 extending to the inferior border resulting in pathologic @entity5 of mandibular bone. Based on these findings, a diagnosis of stage 3 MRONJ was made. We performed conservative treatment, including @entity3 , but his symptoms did not improve. He was then treated with once-weekly subcutaneous injection of @entity10 . Although @entity10 injections were started without antibiotics, after 1 week, @entity1 , erythema, and purulent discharge from the extraoral @entity6 increased rapidly. Therefore, we combined the once-weekly @entity10 injection with @entity3 administration. Three months later, the @entity7 had healed and CT showed significant bone regeneration and healing of the mandibular pathologic @entity5 . In addition, the mandibular @entity6 showed healing and the intraoral @entity6 was covered with normal mucosa.

title: Treatment of XXXX of the Jaw.

answer: @entity7


abstract: 1. Recent molecular genetic studies have implicated the @entity4 gene locus ( @entity4 , at chromosome 19p13.2) in @entity1 in essential @entity2 @entity0 and in the atherogenic lipoprotein phenotype. The present study examined genotypes for the @entity1 -associated ApaLI restriction fragment length polymorphism of @entity4 , and genotypes for a @entity2 -associated RsaI restriction fragment length polymorphism at the @entity6 gene ( @entity6 ) locus, which is linked to @entity4 , in relation to plasma lipids, body mass index and blood pressure in 27 @entity1 and 57 @entity1 Caucasians with severe essential @entity2 , selected on the basis of having parents who were both @entity2 , and in 25 @entity1 and 45 @entity1 normotensive subjects selected on the basis of having parents who were both normotensive after the age of 50 years. 2. Plasma @entity5 and low-density-lipoprotein- @entity3 were elevated in @entity2 @entity0 , but did not differ between the @entity1 and @entity1 @entity2 groups. Significant positive correlations were seen between body mass index and @entity5 and low-density-lipoprotein- @entity3 in the @entity1 and @entity1 @entity2 @entity0 , respectively. In addition, @entity1 @entity2 @entity0 had significantly higher diastolic blood pressure than @entity1 @entity2 @entity0 . 3. The eight @entity1 @entity2 @entity0 who were homozygous for the @entity1 -associated 6.6 kb allele of the ApaLI restriction fragment length polymorphism of @entity4 ('6.6. kb homozygotes') had a significantly higher body mass index [34 +/- 6.0 (SD) kg/m2] than the 18 heterozygotes (29 +/- 2.7 kg/m2) and the single subject who was homozygous for the 9.4 kb allele (29 kg/m2) (P = 0.012 by one-way analysis of variance). The body mass index of the eight @entity2 6.6 kb homozygotes was also greater than the body mass index of 29 +/- 2.4 kg/m2 observed for the eight @entity1 normotensive 6.6 kb homozygotes. In addition, the eight @entity1 @entity2 6.6 kb homozygotes had a higher plasma @entity5 [4.2 +/- 0.77 (SEM) mmol/l] than the 18 @entity1 @entity2 heterozygotes (2.4 +/- 0.33 mmol/l; P = 0.045). Non- @entity1 @entity2 @entity0 showed no significant genotypic differences in relation to the @entity4 restriction fragment length polymorphism. 4. In the normotensive group, however, the frequency of the 6.6 kb allele of the @entity4 ApaLI restriction fragment length polymorphism in @entity1 subjects (0.54) was not significantly greater than in @entity1 subjects (0.48) [cf. the significantly (P = 0.004( different values of 0.63 and 0.39, respectively, in @entity1 and @entity1 @entity2 @entity0 .(ABSTRACT TRUNCATED AT 400 WORDS)

title: Significant relationships of plasma lipids and body mass index with polymorphisms at the linked @entity4 gene and XXXX gene loci (19p13.2) in essential @entity2 @entity0 .

answer: @entity6


abstract: 1. Recent molecular genetic studies have implicated the @entity4 gene locus ( @entity4 , at chromosome 19p13.2) in @entity1 in essential @entity2 @entity0 and in the atherogenic lipoprotein phenotype. The present study examined genotypes for the @entity1 -associated ApaLI restriction fragment length polymorphism of @entity4 , and genotypes for a @entity2 -associated RsaI restriction fragment length polymorphism at the @entity6 gene ( @entity6 ) locus, which is linked to @entity4 , in relation to plasma lipids, body mass index and blood pressure in 27 @entity1 and 57 @entity1 Caucasians with severe essential @entity2 , selected on the basis of having parents who were both @entity2 , and in 25 @entity1 and 45 @entity1 normotensive subjects selected on the basis of having parents who were both normotensive after the age of 50 years. 2. Plasma @entity5 and low-density-lipoprotein- @entity3 were elevated in @entity2 @entity0 , but did not differ between the @entity1 and @entity1 @entity2 groups. Significant positive correlations were seen between body mass index and @entity5 and low-density-lipoprotein- @entity3 in the @entity1 and @entity1 @entity2 @entity0 , respectively. In addition, @entity1 @entity2 @entity0 had significantly higher diastolic blood pressure than @entity1 @entity2 @entity0 . 3. The eight @entity1 @entity2 @entity0 who were homozygous for the @entity1 -associated 6.6 kb allele of the ApaLI restriction fragment length polymorphism of @entity4 ('6.6. kb homozygotes') had a significantly higher body mass index [34 +/- 6.0 (SD) kg/m2] than the 18 heterozygotes (29 +/- 2.7 kg/m2) and the single subject who was homozygous for the 9.4 kb allele (29 kg/m2) (P = 0.012 by one-way analysis of variance). The body mass index of the eight @entity2 6.6 kb homozygotes was also greater than the body mass index of 29 +/- 2.4 kg/m2 observed for the eight @entity1 normotensive 6.6 kb homozygotes. In addition, the eight @entity1 @entity2 6.6 kb homozygotes had a higher plasma @entity5 [4.2 +/- 0.77 (SEM) mmol/l] than the 18 @entity1 @entity2 heterozygotes (2.4 +/- 0.33 mmol/l; P = 0.045). Non- @entity1 @entity2 @entity0 showed no significant genotypic differences in relation to the @entity4 restriction fragment length polymorphism. 4. In the normotensive group, however, the frequency of the 6.6 kb allele of the @entity4 ApaLI restriction fragment length polymorphism in @entity1 subjects (0.54) was not significantly greater than in @entity1 subjects (0.48) [cf. the significantly (P = 0.004( different values of 0.63 and 0.39, respectively, in @entity1 and @entity1 @entity2 @entity0 .(ABSTRACT TRUNCATED AT 400 WORDS)

title: Significant relationships of plasma lipids and body mass index with polymorphisms at the linked XXXX gene and @entity6 gene loci (19p13.2) in essential @entity2 @entity0 .

answer: @entity4


abstract: 1. Recent molecular genetic studies have implicated the @entity4 gene locus ( @entity4 , at chromosome 19p13.2) in @entity1 in essential @entity2 @entity0 and in the atherogenic lipoprotein phenotype. The present study examined genotypes for the @entity1 -associated ApaLI restriction fragment length polymorphism of @entity4 , and genotypes for a @entity2 -associated RsaI restriction fragment length polymorphism at the @entity6 gene ( @entity6 ) locus, which is linked to @entity4 , in relation to plasma lipids, body mass index and blood pressure in 27 @entity1 and 57 @entity1 Caucasians with severe essential @entity2 , selected on the basis of having parents who were both @entity2 , and in 25 @entity1 and 45 @entity1 normotensive subjects selected on the basis of having parents who were both normotensive after the age of 50 years. 2. Plasma @entity5 and low-density-lipoprotein- @entity3 were elevated in @entity2 @entity0 , but did not differ between the @entity1 and @entity1 @entity2 groups. Significant positive correlations were seen between body mass index and @entity5 and low-density-lipoprotein- @entity3 in the @entity1 and @entity1 @entity2 @entity0 , respectively. In addition, @entity1 @entity2 @entity0 had significantly higher diastolic blood pressure than @entity1 @entity2 @entity0 . 3. The eight @entity1 @entity2 @entity0 who were homozygous for the @entity1 -associated 6.6 kb allele of the ApaLI restriction fragment length polymorphism of @entity4 ('6.6. kb homozygotes') had a significantly higher body mass index [34 +/- 6.0 (SD) kg/m2] than the 18 heterozygotes (29 +/- 2.7 kg/m2) and the single subject who was homozygous for the 9.4 kb allele (29 kg/m2) (P = 0.012 by one-way analysis of variance). The body mass index of the eight @entity2 6.6 kb homozygotes was also greater than the body mass index of 29 +/- 2.4 kg/m2 observed for the eight @entity1 normotensive 6.6 kb homozygotes. In addition, the eight @entity1 @entity2 6.6 kb homozygotes had a higher plasma @entity5 [4.2 +/- 0.77 (SEM) mmol/l] than the 18 @entity1 @entity2 heterozygotes (2.4 +/- 0.33 mmol/l; P = 0.045). Non- @entity1 @entity2 @entity0 showed no significant genotypic differences in relation to the @entity4 restriction fragment length polymorphism. 4. In the normotensive group, however, the frequency of the 6.6 kb allele of the @entity4 ApaLI restriction fragment length polymorphism in @entity1 subjects (0.54) was not significantly greater than in @entity1 subjects (0.48) [cf. the significantly (P = 0.004( different values of 0.63 and 0.39, respectively, in @entity1 and @entity1 @entity2 @entity0 .(ABSTRACT TRUNCATED AT 400 WORDS)

title: Significant relationships of plasma lipids and body mass index with polymorphisms at the linked @entity4 gene and @entity6 gene loci (19p13.2) in essential XXXX @entity0 .

answer: @entity2


abstract: 1. Recent molecular genetic studies have implicated the @entity4 gene locus ( @entity4 , at chromosome 19p13.2) in @entity1 in essential @entity2 @entity0 and in the atherogenic lipoprotein phenotype. The present study examined genotypes for the @entity1 -associated ApaLI restriction fragment length polymorphism of @entity4 , and genotypes for a @entity2 -associated RsaI restriction fragment length polymorphism at the @entity6 gene ( @entity6 ) locus, which is linked to @entity4 , in relation to plasma lipids, body mass index and blood pressure in 27 @entity1 and 57 @entity1 Caucasians with severe essential @entity2 , selected on the basis of having parents who were both @entity2 , and in 25 @entity1 and 45 @entity1 normotensive subjects selected on the basis of having parents who were both normotensive after the age of 50 years. 2. Plasma @entity5 and low-density-lipoprotein- @entity3 were elevated in @entity2 @entity0 , but did not differ between the @entity1 and @entity1 @entity2 groups. Significant positive correlations were seen between body mass index and @entity5 and low-density-lipoprotein- @entity3 in the @entity1 and @entity1 @entity2 @entity0 , respectively. In addition, @entity1 @entity2 @entity0 had significantly higher diastolic blood pressure than @entity1 @entity2 @entity0 . 3. The eight @entity1 @entity2 @entity0 who were homozygous for the @entity1 -associated 6.6 kb allele of the ApaLI restriction fragment length polymorphism of @entity4 ('6.6. kb homozygotes') had a significantly higher body mass index [34 +/- 6.0 (SD) kg/m2] than the 18 heterozygotes (29 +/- 2.7 kg/m2) and the single subject who was homozygous for the 9.4 kb allele (29 kg/m2) (P = 0.012 by one-way analysis of variance). The body mass index of the eight @entity2 6.6 kb homozygotes was also greater than the body mass index of 29 +/- 2.4 kg/m2 observed for the eight @entity1 normotensive 6.6 kb homozygotes. In addition, the eight @entity1 @entity2 6.6 kb homozygotes had a higher plasma @entity5 [4.2 +/- 0.77 (SEM) mmol/l] than the 18 @entity1 @entity2 heterozygotes (2.4 +/- 0.33 mmol/l; P = 0.045). Non- @entity1 @entity2 @entity0 showed no significant genotypic differences in relation to the @entity4 restriction fragment length polymorphism. 4. In the normotensive group, however, the frequency of the 6.6 kb allele of the @entity4 ApaLI restriction fragment length polymorphism in @entity1 subjects (0.54) was not significantly greater than in @entity1 subjects (0.48) [cf. the significantly (P = 0.004( different values of 0.63 and 0.39, respectively, in @entity1 and @entity1 @entity2 @entity0 .(ABSTRACT TRUNCATED AT 400 WORDS)

title: Significant relationships of plasma lipids and body mass index with polymorphisms at the linked @entity4 gene and @entity6 gene loci (19p13.2) in essential @entity2 XXXX .

answer: @entity0


abstract: CASE: Emily is a 4 and half-year-old @entity0 whose foster mother is concerned about her odd eating behaviors. Emily has been with her foster mother for 1 year after exposure to domestic violence. Emily's habit of eating nonfood items led to her foster mother providing "100% supervision." Emily constantly picks up, smells, and tastes nonfood items, particularly rocks and things made of metal. She "explores everything with her tongue." Emily scoops dirt and gravel from sidewalk crevices into @entity4 . Although toileting, she catches and licks urine in her hand and searches for stool to put in @entity4 . With redirection, Emily stopped putting feces into @entity4 , but after spending time with her biological family, this behavior recurred.Emily does not like to eat foods that are hard or require chewing. She does not choke or gag on solid foods or liquids. She likes foods that are sweet. She refuses to eat vegetables and foods with certain textures. Emily pulls food apart with her hands before putting it in @entity4 .Emily has @entity1 , @entity2 , @entity3 in her legs, and strabismus. A medical workup resulted in a diagnosis of trisomy 4p and monosomy 9p. Emily works with a physical therapist and occupational therapist; she attends preschool in a special day class. She is an alert, playful, and socially engaging @entity0 who walks with an abnormal gait, speaks in short sentences, and follows simple directions.

title: Pica in a Four-Year-Old @entity0 with XXXX .

answer: @entity1


abstract: CASE: Emily is a 4 and half-year-old @entity0 whose foster mother is concerned about her odd eating behaviors. Emily has been with her foster mother for 1 year after exposure to domestic violence. Emily's habit of eating nonfood items led to her foster mother providing "100% supervision." Emily constantly picks up, smells, and tastes nonfood items, particularly rocks and things made of metal. She "explores everything with her tongue." Emily scoops dirt and gravel from sidewalk crevices into @entity4 . Although toileting, she catches and licks urine in her hand and searches for stool to put in @entity4 . With redirection, Emily stopped putting feces into @entity4 , but after spending time with her biological family, this behavior recurred.Emily does not like to eat foods that are hard or require chewing. She does not choke or gag on solid foods or liquids. She likes foods that are sweet. She refuses to eat vegetables and foods with certain textures. Emily pulls food apart with her hands before putting it in @entity4 .Emily has @entity1 , @entity2 , @entity3 in her legs, and strabismus. A medical workup resulted in a diagnosis of trisomy 4p and monosomy 9p. Emily works with a physical therapist and occupational therapist; she attends preschool in a special day class. She is an alert, playful, and socially engaging @entity0 who walks with an abnormal gait, speaks in short sentences, and follows simple directions.

title: Pica in a Four-Year-Old XXXX with @entity1 .

answer: @entity0


abstract: Phosphorescence spectroscopy and optical detection of triplet state magnetic resonance (ODMR) spectroscopy have been used to characterize bases that contribute to the phosphorescence emission of @entity0 valine-specific transfer ribonucleic acid. When it is excited with 335-nm light, a short-lived phosphorescence with an origin near 435 nm is observed and is assigned to @entity2 ( @entity4 ) at position 8 of the tRNA sequence. With excitation at 290-300 nm, a structured, long-lived phosphorescence is observed with an origin near 380 nm, in addition to the s4U phosphorescence. Comparison was made of the phosphorescence and ODMR spectra between @entity1 -containing and @entity1 -free tRNA samples. The s4U phosphorescence of the @entity1 -containing sample is more structured, and the peak is blue shifted relative to the @entity1 -free sample. Both samples give a single low-frequency (ca. 2.9 GHz) ODMR signal, but the high-frequency signal region (ca. 19-20 GHz) is structured. The @entity1 -containing sample has a partially resolved group of lines centered at 19.3 GHz, whereas the @entity1 -free sample has two broad bands centered at 19.2 and 20.0 gHz. The differences are attributed to effects of @entity1 on the tRNA conformation. The ODMR signals observed by monitoring the long-lived phosphorescence are assigned to a @entity3 , possibly @entity5 in the anticodon.

title: Optically detected magnetic resonance of the phosphorescent bases of XXXX valine-specific transfer ribonucleic acid.

answer: @entity0


abstract: BACKGROUND: The extent of noninvasive ventilation (NIV) use for @entity0 with @entity2 in Canadian hospitals, indications for use and associated outcomes are unknown. OBJECTIVE: To describe NIV practice variation in the acute setting. METHODS: A prospective observational study involving 11 Canadian tertiary care centres was performed. Data regarding NIV indication, mode and outcomes were collected for all adults (>16 years of age) treated with NIV for @entity2 during a four-week period (between February and August 2011). Logistic regression with site as a random effect was used to examine the association between preselected predictors and mortality or intubation. RESULTS: A total of 330 @entity0 (mean [   SD] 30  12 per centre) were included. The most common indications for NIV initiation were @entity3 (104 [31.5%]) and @entity1 (99 [30.0%]). Significant differences in indications for NIV use across sites, specialty of ordering physician and location of NIV initiation were noted. Although intubation rates were not statistically different among sites (range 10.3% to 45.4%), mortality varied significantly (range 6.7% to 54.5%; P=0.006). In multivariate analysis, the most significant independent predictor of avoiding intubation was do-not-resuscitate status (OR 0.11 [95% CI 0.03 to 0.37]). CONCLUSION: Significant variability existed in NIV use and associated outcomes among Canadian tertiary care centres. Assignment of do-not-resuscitate status prevented intubation.

title: Noninvasive ventilation practice patterns for XXXX in Canadian tertiary care centres: A descriptive analysis.

answer: @entity2


abstract: The clinical course of 15 @entity0 with overt @entity4 manifested in childhood were studied. Nine female @entity0 with @entity4 due to @entity6 showed almost normal height and became euthyroid spontaneously during @entity5 restriction. The other 6 nongoitrous @entity0 (3M and 3F) ( @entity3 in 2, @entity7 in 2 and probable hypoplastic thyroid in 2) showed physical @entity1 and remained irreversibly @entity4 requiring replacement therapy. In the reversible group, the characteristic findings were high thyroidal radioactive @entity5 uptake (58 +/- 19%/24 h, N = 8) and positive perchlorate discharge test. Serum nonhormonal @entity5 levels were high in 4 of 6 @entity0 measured. During the long-term follow-up period of 6 years in 6 @entity0 , 2 @entity0 remained euthyroid with normal growth and regular menstrual cycle and 4 @entity0 became @entity4 again (after eating seaweed in 1, despite @entity5 restriction in 2 and after the episode of @entity3 in 1). @entity2 of growth was observed during the second episode of @entity4 . In the irreversible group, one @entity0 with blocking type TSH binding inhibitor immunoglobulin (TBII) became thyrotoxic 4 years later with the decrease in activity of blocking type TBII. These results suggested that reversible recovery of the thyroid function could be expected in @entity0 with @entity4 due to @entity6 after (1) @entity5 restriction, (2) improvement of immunological perturbation, or (3) disappearance of blocking type TBII. However, careful follow-up is necessary, because @entity4 would recur again with transient retardation of growth in @entity0 .

title: @entity4 manifested in childhood with special reference to various types of reversible XXXX .

answer: @entity4


abstract: The clinical course of 15 @entity0 with overt @entity4 manifested in childhood were studied. Nine female @entity0 with @entity4 due to @entity6 showed almost normal height and became euthyroid spontaneously during @entity5 restriction. The other 6 nongoitrous @entity0 (3M and 3F) ( @entity3 in 2, @entity7 in 2 and probable hypoplastic thyroid in 2) showed physical @entity1 and remained irreversibly @entity4 requiring replacement therapy. In the reversible group, the characteristic findings were high thyroidal radioactive @entity5 uptake (58 +/- 19%/24 h, N = 8) and positive perchlorate discharge test. Serum nonhormonal @entity5 levels were high in 4 of 6 @entity0 measured. During the long-term follow-up period of 6 years in 6 @entity0 , 2 @entity0 remained euthyroid with normal growth and regular menstrual cycle and 4 @entity0 became @entity4 again (after eating seaweed in 1, despite @entity5 restriction in 2 and after the episode of @entity3 in 1). @entity2 of growth was observed during the second episode of @entity4 . In the irreversible group, one @entity0 with blocking type TSH binding inhibitor immunoglobulin (TBII) became thyrotoxic 4 years later with the decrease in activity of blocking type TBII. These results suggested that reversible recovery of the thyroid function could be expected in @entity0 with @entity4 due to @entity6 after (1) @entity5 restriction, (2) improvement of immunological perturbation, or (3) disappearance of blocking type TBII. However, careful follow-up is necessary, because @entity4 would recur again with transient retardation of growth in @entity0 .

title: XXXX manifested in childhood with special reference to various types of reversible @entity4 .

answer: @entity4


abstract: 1. The characteristics of adrenoceptors mediating relaxation to @entity4 in @entity0 isolated jejunum were investigated. 2. @entity4 and @entity6 produced relaxation of the @entity8 -contracted strips with an order of potency of @entity5 (1.0) > @entity6 (0.63) > @entity1 (0.1) > @entity3 (0.04). 3. In the presence of both @entity7 (1 microM) and @entity2 (1 microM) only small dextral shifts of the concentration-response curves to agonists were observed and an order of potency of @entity6 (2.5) > @entity5 (1.0) > @entity1 (0.2) > @entity3 (0.1) was obtained. 4. In the presence of @entity7 (1 microM) and @entity2 (1 microM), @entity9 (0.1-10 microM) produced a concentration-dependent rightward shift of the concentration-response curve to @entity3 with a Schild slope not significantly different from unity and a mean pA2 value of 7.01. 5. The resistance of relaxant responses to @entity2 , the relatively high potency of @entity6 compared to @entity4 and the competitive antagonism of relaxant responses to @entity3 by @entity9 suggest that beta-adrenoceptors in @entity0 small intestine are mainly atypical in nature.

title: Adrenoceptors mediating relaxation to XXXX in @entity0 isolated jejunum.

answer: @entity4


abstract: 1. The characteristics of adrenoceptors mediating relaxation to @entity4 in @entity0 isolated jejunum were investigated. 2. @entity4 and @entity6 produced relaxation of the @entity8 -contracted strips with an order of potency of @entity5 (1.0) > @entity6 (0.63) > @entity1 (0.1) > @entity3 (0.04). 3. In the presence of both @entity7 (1 microM) and @entity2 (1 microM) only small dextral shifts of the concentration-response curves to agonists were observed and an order of potency of @entity6 (2.5) > @entity5 (1.0) > @entity1 (0.2) > @entity3 (0.1) was obtained. 4. In the presence of @entity7 (1 microM) and @entity2 (1 microM), @entity9 (0.1-10 microM) produced a concentration-dependent rightward shift of the concentration-response curve to @entity3 with a Schild slope not significantly different from unity and a mean pA2 value of 7.01. 5. The resistance of relaxant responses to @entity2 , the relatively high potency of @entity6 compared to @entity4 and the competitive antagonism of relaxant responses to @entity3 by @entity9 suggest that beta-adrenoceptors in @entity0 small intestine are mainly atypical in nature.

title: Adrenoceptors mediating relaxation to @entity4 in XXXX isolated jejunum.

answer: @entity0


abstract: 1. Pharmacological experiments on vascular tissue are normally performed on isometric ring or strip preparations. The aim of this study was to compare the isometric characteristics with the characteristics obtained if vessels were examined under the more physiologically appropriate isobaric condition. 2. @entity0 mesenteric small arteries were mounted either on two steel wires for isometric force measurement (wire-myograph) or cannulated for measurement of the internal diameter under isobaric conditions (pressure-myograph). 3. The passive pressure-diameter characteristics of the small arteries were similar on the wire- and pressure-myograph (using the Laplace relation to convert wall tension-internal circumference data from the wire-myograph to effective pressure-diameter characteristics). 4. In cumulative concentration-response experiments with @entity2 and @entity5 , the threshold concentration was 8-10 times lower, and the EC50-concentration was 4-5 times lower, in the pressure myograph compared to the wire-myograph. Thus vessels were not only more sensitive on the pressure myograph, but the slopes of the concentration-response curves were less steep. Similar experiments with @entity3 also showed this difference in the threshold-concentration and slope, but EC50 concentrations were similar. 5. Cumulative concentration-response experiments with K+ showed no difference either in EC50 or in slope on the wire- and pressure-myographs. 6. On the wire-myograph, some vessels were stretched longitudinally (to mimic the longitudinal stretch which had to be used in the pressure-myograph to avoid buckling). Such stretch did not affect the passive characteristics. 7. The differences between the EC50 determined on the wire- and pressure-myographs as regards @entity2 and @entity5 were eliminated when neuronal @entity2 uptake was inhibited by denervation. However, the slope of the concentration-response curves on the wire-myograph was not affected by denervation.8. When vessels were exposed to @entity4 (3 MicroM) the @entity2 concentration-response curves were the same on the wire- and pressure-myographs as regards both EC50 and slope.9. On the wire-myograph, the @entity1 antagonist, @entity6 , (D600) reduced the maximal contractile effect of @entity2 by 50%, but on the pressure-myograph D600 did not affect the maximal response.10. The present results show that results obtained from vascular tissue under isometric conditions may differ substantially from the characteristics which would be obtained under isobaric conditions.

title: Differences in sensitivity of XXXX mesenteric small arteries to agonists when studied as ring preparations or as cannulated preparations.

answer: @entity0


abstract: BACKGROUND: We previously identified a @entity2 signature of @entity6 , @entity8 , @entity7 , and @entity9 that, together with clinical features, was associated with lethal outcomes among @entity4 @entity0 . In the current study, we sought to validate the molecular model using time-dependent measures of AUC and predictive values for discriminating lethal from non-lethal @entity4 . METHODS: Using data from the initial study, we fit survival models for @entity0 with @entity4 who were @entity0 in the Physicians' Health Study (PHS; n   =   276). Based on these models, we generated prognostic risk scores in an independent population, the @entity5 ( @entity5 ; n   =   347) to evaluate external validity. In each cohort, @entity0 were followed prospectively from @entity2 diagnosis through 2011 for development of distant @entity1 or @entity2 mortality. We measured @entity2 expression of @entity6 , @entity8 , @entity7 , and @entity9 on tissue microarrays. RESULTS: During a median of 11.9 and 14.3 years follow-up in the PHS and @entity5 cohorts, 24 and 32 @entity0 (9%) developed @entity3 . When used as a prognostic factor in a new population, addition of the four markers to clinical variables did not improve discriminatory accuracy through 15 years of follow-up. CONCLUSIONS: Although the four markers have been identified as key biological mediators in metastatic progression, they do not provide independent, long-term prognostic information beyond clinical factors when measured at diagnosis. This finding may underscore the broad heterogeneity in @entity4 and highlight the challenges that may result from overfitting in discovery-based research.

title: Evaluating a 4-marker signature of XXXX using time-dependent AUC.

answer: @entity4


abstract: We have purified a soluble @entity0 reticulocyte protein, previously termed the supernatant factor, that reverses the inhibition of protein synthesis in hemin-deficient lysate by promoting the inactivation of the hemin-controlled eIF-2 alpha kinase (HCR) mediating the effect of @entity3 . We have identified the supernatant factor as a member of the @entity5 protein 70 family, denoted hsp 70(R), based upon its size (72 kDa), specific reaction to a monoclonal antibody against eukaryotic hsp 70, strong binding affinity for @entity2 , and endogenous ATPase activity. We have investigated the role of hsp 70(R) and hemin in the regulation of the activation of HCR from its latent precursor (ProHCR) and the translational control of protein synthesis in @entity0 reticulocyte lysate. We find that autophosphorylation of Pro-HCR is reduced by about 75% by adding saturating hsp 70(R) and almost completely reduced by adding either saturating hemin or limiting hemin plus limiting hsp 70(R). In contrast, autophosphorylation of HCR, which is similar in magnitude to that of ProHCR, is unaffected by adding either saturating hsp 70(R), saturating hemin, or limiting amounts of both. The activation of HCR (measured by inhibition of protein synthesis) from isolated ProHCR is completely prevented by hsp 70(R) in the presence, but not absence, of @entity6 . This suppression appears to be due to the association of hsp 70(R) with ProHCR, since hsp 70(R) action is prevented by @entity2 /Mg2+ and because activation of HCR from less purified ProHCR, that has associated hsp 70(R), is suppressed by @entity6 alone. This association is confirmed by @entity4 gradient centrifugation, which shows co-sedimentation of some hsp 70(R) with ProHCR following preincubation together that is prevented by @entity2 /Mg2+ and does not occur after conversion of ProHCR to HCR. Limiting hsp 70(R) reduces the concentration of hemin required to prevent activation of HCR from isolated ProHCR from 0.75 to 0.15 microM and the optimal hemin concentration needed to maintain protein synthesis in reticulocyte lysate from 25 to 10 microM. Limiting hsp 70(R) also allows the delayed addition of hemin to suppress activation of HCR from ProHCR and to reverse inhibition of protein synthesis in hemin deficient lysate. The association of hsp 70(R) with ProHCR also underlies the observation that much more protein is synthesized in reticulocyte lysate in the absence of hemin at 25 degrees C than at temperatures of 30 degrees C or greater. These observed effects may be specific to hsp 70(R), since they are not observed with @entity0 reticulocyte eIF-2 or eIF-2B, and since the comparable hsp 70 from @entity1 brain is incapable of maintaining or restoring protein synthesis in hemin-deficient lysate.

title: Control of protein synthesis by hemin. Purification of a XXXX reticulocyte hsp 70 and characterization of its regulation of the activation of the hemin-controlled eIF-2(alpha) kinase.

answer: @entity0


abstract: BACKGROUND: @entity8 is a long-acting @entity1 -agonist drug that suppresses prolactin secretion and restores gonadal function in @entity0 with hyperprolactinemic @entity4 . We designed a study to compare its safety and efficacy with those of @entity5 , which has been the standard therapy. METHODS: A total of 459 @entity0 with hyperprolactinemic @entity4 were treated with either @entity8 (0.5 to 1.0 mg twice weekly) or @entity5 (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 @entity0 , 279 had @entity3 , 3 had @entity3 , 1 had a @entity2 , 167 had idiopathic @entity6 , and the remainder had an @entity7 . Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. RESULTS: Stable normoprolactinemia was achieved in 186 of the 223 @entity0 treated with @entity8 (83 percent) and 138 of the 236 @entity0 treated with @entity5 (59 percent, P < 0.001). Seventy-two percent of the @entity0 treated with @entity8 and 52 percent of those treated with @entity5 had ovulatory cycles or became pregnant during treatment (P < 0.001). @entity4 persisted in 7 percent of the @entity8 -treated @entity0 and 16 percent of the @entity5 -treated @entity0 . Adverse effects were recorded in 68 percent of the @entity0 taking @entity8 and 78 percent of those taking @entity5 (P = 0.03); 3 percent discontinued taking @entity8 , and 12 percent stopped taking @entity5 (P < 0.001) because of drug intolerance. Gastrointestinal symptoms were significantly less frequent, less severe, and shorter-lived in the @entity0 treated with @entity8 . CONCLUSIONS: @entity8 is more effective and better tolerated than @entity5 in @entity0 with hyperprolactinemic @entity4 .

title: A comparison of @entity8 and XXXX in the treatment of hyperprolactinemic @entity4 . @entity8 Comparative Study Group.

answer: @entity5


abstract: BACKGROUND: @entity8 is a long-acting @entity1 -agonist drug that suppresses prolactin secretion and restores gonadal function in @entity0 with hyperprolactinemic @entity4 . We designed a study to compare its safety and efficacy with those of @entity5 , which has been the standard therapy. METHODS: A total of 459 @entity0 with hyperprolactinemic @entity4 were treated with either @entity8 (0.5 to 1.0 mg twice weekly) or @entity5 (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 @entity0 , 279 had @entity3 , 3 had @entity3 , 1 had a @entity2 , 167 had idiopathic @entity6 , and the remainder had an @entity7 . Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. RESULTS: Stable normoprolactinemia was achieved in 186 of the 223 @entity0 treated with @entity8 (83 percent) and 138 of the 236 @entity0 treated with @entity5 (59 percent, P < 0.001). Seventy-two percent of the @entity0 treated with @entity8 and 52 percent of those treated with @entity5 had ovulatory cycles or became pregnant during treatment (P < 0.001). @entity4 persisted in 7 percent of the @entity8 -treated @entity0 and 16 percent of the @entity5 -treated @entity0 . Adverse effects were recorded in 68 percent of the @entity0 taking @entity8 and 78 percent of those taking @entity5 (P = 0.03); 3 percent discontinued taking @entity8 , and 12 percent stopped taking @entity5 (P < 0.001) because of drug intolerance. Gastrointestinal symptoms were significantly less frequent, less severe, and shorter-lived in the @entity0 treated with @entity8 . CONCLUSIONS: @entity8 is more effective and better tolerated than @entity5 in @entity0 with hyperprolactinemic @entity4 .

title: A comparison of XXXX and @entity5 in the treatment of hyperprolactinemic @entity4 . @entity8 Comparative Study Group.

answer: @entity8


abstract: BACKGROUND: @entity8 is a long-acting @entity1 -agonist drug that suppresses prolactin secretion and restores gonadal function in @entity0 with hyperprolactinemic @entity4 . We designed a study to compare its safety and efficacy with those of @entity5 , which has been the standard therapy. METHODS: A total of 459 @entity0 with hyperprolactinemic @entity4 were treated with either @entity8 (0.5 to 1.0 mg twice weekly) or @entity5 (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 @entity0 , 279 had @entity3 , 3 had @entity3 , 1 had a @entity2 , 167 had idiopathic @entity6 , and the remainder had an @entity7 . Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. RESULTS: Stable normoprolactinemia was achieved in 186 of the 223 @entity0 treated with @entity8 (83 percent) and 138 of the 236 @entity0 treated with @entity5 (59 percent, P < 0.001). Seventy-two percent of the @entity0 treated with @entity8 and 52 percent of those treated with @entity5 had ovulatory cycles or became pregnant during treatment (P < 0.001). @entity4 persisted in 7 percent of the @entity8 -treated @entity0 and 16 percent of the @entity5 -treated @entity0 . Adverse effects were recorded in 68 percent of the @entity0 taking @entity8 and 78 percent of those taking @entity5 (P = 0.03); 3 percent discontinued taking @entity8 , and 12 percent stopped taking @entity5 (P < 0.001) because of drug intolerance. Gastrointestinal symptoms were significantly less frequent, less severe, and shorter-lived in the @entity0 treated with @entity8 . CONCLUSIONS: @entity8 is more effective and better tolerated than @entity5 in @entity0 with hyperprolactinemic @entity4 .

title: A comparison of @entity8 and @entity5 in the treatment of hyperprolactinemic @entity4 . XXXX Comparative Study Group.

answer: @entity8


abstract: BACKGROUND: @entity8 is a long-acting @entity1 -agonist drug that suppresses prolactin secretion and restores gonadal function in @entity0 with hyperprolactinemic @entity4 . We designed a study to compare its safety and efficacy with those of @entity5 , which has been the standard therapy. METHODS: A total of 459 @entity0 with hyperprolactinemic @entity4 were treated with either @entity8 (0.5 to 1.0 mg twice weekly) or @entity5 (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 @entity0 , 279 had @entity3 , 3 had @entity3 , 1 had a @entity2 , 167 had idiopathic @entity6 , and the remainder had an @entity7 . Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. RESULTS: Stable normoprolactinemia was achieved in 186 of the 223 @entity0 treated with @entity8 (83 percent) and 138 of the 236 @entity0 treated with @entity5 (59 percent, P < 0.001). Seventy-two percent of the @entity0 treated with @entity8 and 52 percent of those treated with @entity5 had ovulatory cycles or became pregnant during treatment (P < 0.001). @entity4 persisted in 7 percent of the @entity8 -treated @entity0 and 16 percent of the @entity5 -treated @entity0 . Adverse effects were recorded in 68 percent of the @entity0 taking @entity8 and 78 percent of those taking @entity5 (P = 0.03); 3 percent discontinued taking @entity8 , and 12 percent stopped taking @entity5 (P < 0.001) because of drug intolerance. Gastrointestinal symptoms were significantly less frequent, less severe, and shorter-lived in the @entity0 treated with @entity8 . CONCLUSIONS: @entity8 is more effective and better tolerated than @entity5 in @entity0 with hyperprolactinemic @entity4 .

title: A comparison of @entity8 and @entity5 in the treatment of hyperprolactinemic XXXX . @entity8 Comparative Study Group.

answer: @entity4


abstract: Mechanisms of the analgesic actions of alpha 2-adrenergic agonists are likely related to various modulating systems of nociceptive neurotransmission, especially those dependent on opiate receptors. Analgesic action of alpha 2-adrenergic agonists implies alpha 2-adrenergic receptors, strategically located on the dorsal horn neurones of the spinal cord to inhibit the release of @entity4 in response to peripheral stimuli. However, these receptors are included in the control that supraspinal sites exert via the descending medullospinal noradrenergic pathway. Because of its high lipophilic structure, alpha 2-adrenergic agonist can easily penetrate into the central nervous system, reproducing the effects of activation of medullospinal noradrenergic pathway. Alpha 2-adrenergic agonists have been found to be efficient in @entity0 @entity1 treatment after systemic, spinal or troncular administration, but there were few randomized clinical studies comparing @entity2 potency and adverse effects of either systemic or regional administrations. @entity3 added to local anaesthetic agents increases the analgesic effects in a greater extent than systemic administration of similar dose, probably because this effect depends on the local @entity3 concentration. Extradural administration of @entity3 is also more efficient than systemic administration, at least when high doses are injected. This superiority is questionable when low-dose @entity3 is used. Adverse effects are quite similar in both systemic and spinal routes. Invasiveness of extradural route may be considered in regard to the gain which may be expected in @entity2 efficiency.

title: [Which way for the administration of alpha 2-adrenergic agents to obtain the best XXXX ?].

answer: @entity2


abstract: The @entity6 catalyzes the first three steps in de novo @entity4 biosynthesis in @entity0 cells. @entity3 -dependent @entity5 synthetase (CPSase), @entity1 transcarbamylase, and dihydroorotase activities are carried by a 243-kDa polypeptide chain that is organized into discrete functional domains connected by interdomain linkers. One of the connecting chain segments, the DA linker bridging the dihydroorotase and @entity1 transcarbamylase domains, is unusually long (109 residues) and conserved in length in all eukaryotic species. A plasmid (pCK-CAD10) that encodes the entire 243-kDa polypeptide was constructed and expressed in @entity2 . The recombinant protein was purified to homogeneity by ion exchange and gel filtration chromatography. The purified protein had kinetic parameters that were close to those obtained for native CAD. Moreover, the CPSase activity was allosterically regulated. Gel filtration showed that the recombinant protein had the same molecular mass as native CAD. Thus, this complex @entity0 protein is expressed and folds correctly in bacterial cells and, despite its extreme protease sensitivity, can be isolated intact. A deletion mutant that lacked the DA linker was then constructed. The kinetic parameters of the mutant protein were, for the most part, unaltered, showing that the DA linker is not essential for the proper folding or optimal functioning of the individual domains. However, a significant decrease in the thermal stability of the CPSase domain suggested that the linker helps to stabilize the complex. Moreover, the channeling of @entity5 , determined by measuring the extent to which the exogenously added intermediate could dilute the endogenous @entity5 pool, was appreciably reduced when the DA linker was removed. Thus, although the domains function autonomously, some of the linkers are important for interdomain interactions in CAD.

title: Cloning and expression of the @entity0 @entity6 in XXXX . Characterization of the recombinant protein and a deletion mutant lacking the major interdomain linker.

answer: @entity2


abstract: The @entity6 catalyzes the first three steps in de novo @entity4 biosynthesis in @entity0 cells. @entity3 -dependent @entity5 synthetase (CPSase), @entity1 transcarbamylase, and dihydroorotase activities are carried by a 243-kDa polypeptide chain that is organized into discrete functional domains connected by interdomain linkers. One of the connecting chain segments, the DA linker bridging the dihydroorotase and @entity1 transcarbamylase domains, is unusually long (109 residues) and conserved in length in all eukaryotic species. A plasmid (pCK-CAD10) that encodes the entire 243-kDa polypeptide was constructed and expressed in @entity2 . The recombinant protein was purified to homogeneity by ion exchange and gel filtration chromatography. The purified protein had kinetic parameters that were close to those obtained for native CAD. Moreover, the CPSase activity was allosterically regulated. Gel filtration showed that the recombinant protein had the same molecular mass as native CAD. Thus, this complex @entity0 protein is expressed and folds correctly in bacterial cells and, despite its extreme protease sensitivity, can be isolated intact. A deletion mutant that lacked the DA linker was then constructed. The kinetic parameters of the mutant protein were, for the most part, unaltered, showing that the DA linker is not essential for the proper folding or optimal functioning of the individual domains. However, a significant decrease in the thermal stability of the CPSase domain suggested that the linker helps to stabilize the complex. Moreover, the channeling of @entity5 , determined by measuring the extent to which the exogenously added intermediate could dilute the endogenous @entity5 pool, was appreciably reduced when the DA linker was removed. Thus, although the domains function autonomously, some of the linkers are important for interdomain interactions in CAD.

title: Cloning and expression of the @entity0 XXXX in @entity2 . Characterization of the recombinant protein and a deletion mutant lacking the major interdomain linker.

answer: @entity6


abstract: The @entity6 catalyzes the first three steps in de novo @entity4 biosynthesis in @entity0 cells. @entity3 -dependent @entity5 synthetase (CPSase), @entity1 transcarbamylase, and dihydroorotase activities are carried by a 243-kDa polypeptide chain that is organized into discrete functional domains connected by interdomain linkers. One of the connecting chain segments, the DA linker bridging the dihydroorotase and @entity1 transcarbamylase domains, is unusually long (109 residues) and conserved in length in all eukaryotic species. A plasmid (pCK-CAD10) that encodes the entire 243-kDa polypeptide was constructed and expressed in @entity2 . The recombinant protein was purified to homogeneity by ion exchange and gel filtration chromatography. The purified protein had kinetic parameters that were close to those obtained for native CAD. Moreover, the CPSase activity was allosterically regulated. Gel filtration showed that the recombinant protein had the same molecular mass as native CAD. Thus, this complex @entity0 protein is expressed and folds correctly in bacterial cells and, despite its extreme protease sensitivity, can be isolated intact. A deletion mutant that lacked the DA linker was then constructed. The kinetic parameters of the mutant protein were, for the most part, unaltered, showing that the DA linker is not essential for the proper folding or optimal functioning of the individual domains. However, a significant decrease in the thermal stability of the CPSase domain suggested that the linker helps to stabilize the complex. Moreover, the channeling of @entity5 , determined by measuring the extent to which the exogenously added intermediate could dilute the endogenous @entity5 pool, was appreciably reduced when the DA linker was removed. Thus, although the domains function autonomously, some of the linkers are important for interdomain interactions in CAD.

title: Cloning and expression of the XXXX @entity6 in @entity2 . Characterization of the recombinant protein and a deletion mutant lacking the major interdomain linker.

answer: @entity0


abstract: BACKGROUND: Data on the analgesic properties of alpha 2 agonists and their interactions with opioids are conflicting. Experiments were conducted in @entity0 to evaluate whether various available alpha 2 agonists can potentiate the analgesic properties of opioids and to determine the route of administration needed for optimal interaction. METHODS: The tail-withdrawal reaction test was used as an @entity2 assay. In separate experiments, the interactions between systemic (subcutaneous, intravenous, and intraperitoneal) and spinally (epidural and intrathecal) administered alpha 2 agonists and opioids were evaluated. The antagonism of @entity9 plus @entity5 with @entity4 and/or @entity10 also was studied. RESULTS: All alpha 2 agonists tested, when injected subcutaneously with @entity5 , potentiated the opioid-induced @entity2 . In terms of a reduction of the amount of @entity5 needed to produce a deep surgical @entity2 (tail-withdrawal reaction latency > or = 10 s) over more than 2 h, the relative order of potency of the alpha 2 agonists tested was: @entity9 > @entity8 > @entity6 > @entity3 > @entity7 . For some of these alpha 2 agonists there was a biphasic effect: at the larger doses tested, a reduction in the @entity5 potentiation was present. The potentiation of the opioid activity with alpha 2 agonists was also demonstrated in terms of a longer duration of @entity2 after combined treatment with fixed doses of opioids. The interaction between the alpha 2 agonists and the opioids remained present when a more profound criterion of @entity2 (tail-withdrawal reaction latency > or = 30 s) was used. Furthermore, the interactions between the alpha 2 agonists tested and @entity5 or @entity1 appeared to be independent of the route of administration. Potentiations were observed after simultaneous subcutaneous injections of both groups of compounds, after the combination of intraperitoneal (alpha 2 agonist) plus subcutaneous (opioid), intravenous (alpha 2 agonist) plus epidural (opioid) and simultaneous epidural or intrathecal administrations. With regard to antagonism of the analgesic activity of combined treatment with alpha 2 agonists plus opioids, @entity4 provided total antagonism, whereas the alpha 2 antagonist @entity10 overcame only the alpha 2 agonist-induced potentiation of @entity5 . CONCLUSIONS: The tested alpha 2 agonists can potentiate the analgesic properties of opioids, but they have no intrinsic antinociceptive effects on spinal reflexes on their own. The potentiating activities of the alpha 2 agonists could be measured both in terms of a reduction of the amount of opioid needed to reach a particular level of @entity2 and in terms of a longer duration of @entity2 with a fixed dose of the opioid. The potentiations were observed with various alpha 2 agonists and opioids and appeared independent of the routes of administration.

title: Potentiation of the analgesic properties of XXXX -like opioids with alpha 2-adrenoceptor agonists in @entity0 .

answer: @entity5


abstract: BACKGROUND: Data on the analgesic properties of alpha 2 agonists and their interactions with opioids are conflicting. Experiments were conducted in @entity0 to evaluate whether various available alpha 2 agonists can potentiate the analgesic properties of opioids and to determine the route of administration needed for optimal interaction. METHODS: The tail-withdrawal reaction test was used as an @entity2 assay. In separate experiments, the interactions between systemic (subcutaneous, intravenous, and intraperitoneal) and spinally (epidural and intrathecal) administered alpha 2 agonists and opioids were evaluated. The antagonism of @entity9 plus @entity5 with @entity4 and/or @entity10 also was studied. RESULTS: All alpha 2 agonists tested, when injected subcutaneously with @entity5 , potentiated the opioid-induced @entity2 . In terms of a reduction of the amount of @entity5 needed to produce a deep surgical @entity2 (tail-withdrawal reaction latency > or = 10 s) over more than 2 h, the relative order of potency of the alpha 2 agonists tested was: @entity9 > @entity8 > @entity6 > @entity3 > @entity7 . For some of these alpha 2 agonists there was a biphasic effect: at the larger doses tested, a reduction in the @entity5 potentiation was present. The potentiation of the opioid activity with alpha 2 agonists was also demonstrated in terms of a longer duration of @entity2 after combined treatment with fixed doses of opioids. The interaction between the alpha 2 agonists and the opioids remained present when a more profound criterion of @entity2 (tail-withdrawal reaction latency > or = 30 s) was used. Furthermore, the interactions between the alpha 2 agonists tested and @entity5 or @entity1 appeared to be independent of the route of administration. Potentiations were observed after simultaneous subcutaneous injections of both groups of compounds, after the combination of intraperitoneal (alpha 2 agonist) plus subcutaneous (opioid), intravenous (alpha 2 agonist) plus epidural (opioid) and simultaneous epidural or intrathecal administrations. With regard to antagonism of the analgesic activity of combined treatment with alpha 2 agonists plus opioids, @entity4 provided total antagonism, whereas the alpha 2 antagonist @entity10 overcame only the alpha 2 agonist-induced potentiation of @entity5 . CONCLUSIONS: The tested alpha 2 agonists can potentiate the analgesic properties of opioids, but they have no intrinsic antinociceptive effects on spinal reflexes on their own. The potentiating activities of the alpha 2 agonists could be measured both in terms of a reduction of the amount of opioid needed to reach a particular level of @entity2 and in terms of a longer duration of @entity2 with a fixed dose of the opioid. The potentiations were observed with various alpha 2 agonists and opioids and appeared independent of the routes of administration.

title: Potentiation of the analgesic properties of @entity5 -like opioids with alpha 2-adrenoceptor agonists in XXXX .

answer: @entity0


abstract: The possibility of @entity2 caused by @entity9 has been supported by anatomo-clinical findings, stereotaxic surgery and more recently by radiological investigations with new techniques, i.e. ct and brain scan. A case of thalamic @entity5 investigated with these techniques and the Luria's neuropsychological test is reported in this paper. The case concerns a 50 years old @entity0 who developed a @entity6 with marked @entity8 . C.T. and radioisotope brain scan revealed a left capsular @entity4 with involvement of thalamic structures. Later, when this @entity0 's @entity5 decreased, Luria's test showed reduction of spontaneous speech, @entity7 , @entity2 , distractibility without @entity1 and repitition. These findings are similar to those reported by some AA. in @entity9 and similar to aphasic syndromes caused by @entity3 . Another important observation was the presence of widespread cortical functional disorder involving the left fronto-temporo-parietal region without evidence of cortical anatomical alteration. The above data and those reported in the literature suggest a very close relationship between thalamic structures, other central nuclei and cortical areas particularly in the control of speech.

title: [On a case of XXXX with @entity9 (author's transl)].

answer: @entity5


abstract: The possibility of @entity2 caused by @entity9 has been supported by anatomo-clinical findings, stereotaxic surgery and more recently by radiological investigations with new techniques, i.e. ct and brain scan. A case of thalamic @entity5 investigated with these techniques and the Luria's neuropsychological test is reported in this paper. The case concerns a 50 years old @entity0 who developed a @entity6 with marked @entity8 . C.T. and radioisotope brain scan revealed a left capsular @entity4 with involvement of thalamic structures. Later, when this @entity0 's @entity5 decreased, Luria's test showed reduction of spontaneous speech, @entity7 , @entity2 , distractibility without @entity1 and repitition. These findings are similar to those reported by some AA. in @entity9 and similar to aphasic syndromes caused by @entity3 . Another important observation was the presence of widespread cortical functional disorder involving the left fronto-temporo-parietal region without evidence of cortical anatomical alteration. The above data and those reported in the literature suggest a very close relationship between thalamic structures, other central nuclei and cortical areas particularly in the control of speech.

title: [On a case of @entity5 with XXXX (author's transl)].

answer: @entity9


abstract: 65 consecutive @entity1 stenosis reconstructions for the treatment of severe @entity2 are reported. 63% of the cases were males, 37% females. The disease was caused by @entity4 in 66% of cases and in 23% by @entity3 or other pathological changes of the @entity1 ; the mean age was 47 in the former. and 31 years in the latter group. An aortorenal saphenous vein bypass was performed in 35% cases, a dacron graft was used in 29% and thrombendarteriectomy was carried out in 23% cases. Positive results were achieved in 68.8% of the @entity0 . 63% of the females became normotensive. Operative mortality due to faulty technique was 4.9% initially. The operative mortality has been zero since 1973. nor have there been any therapeutic failures on a technical basis. No significant correlation was established between age of the @entity0 and result of operation.

title: [Problems arising in connection with surgical management of XXXX (author's transl)].

answer: @entity2


abstract: The activation and subsequent differentiation of naive CD4+ T cells into functionally distinct effector cells is a vital step in the generation of an effective immune response to protein antigens. To analyse the development of effector T cells following the activation of resting, naive CD4+ T cells, we have utilized a transgenic @entity0 model in which the majority of T cells express a common T-cell receptor V beta molecule. The resting T cells were purified and stimulated in vitro with staphylococcal enterotoxin B, in the presence of accessory cells expressing class II major histocompatibility complex (MHC) molecules. We found that the cells which developed from these primary cultures were capable of producing varying levels of @entity5 ( @entity5 ), @entity1 and @entity2 ( @entity2 ) following restimulation with anti-V beta 8 antibody, irrespective of whether B cells or macrophages/dendritic cells were the accessory cells in the primary cultures. The addition of @entity1 during primary stimulation enhanced the differentiation of @entity1 -producing cells and suppressed the expansion of @entity2 -producing cells, especially when B cells were the @entity3 ( @entity3 ). Neutralization of endogenously produced @entity6 , even in the presence of exogenous @entity1 , did not inhibit the differentiation of @entity1 -producing T cells. Strikingly, @entity4 completely suppressed the development of effector T cells when adherent macrophages/dendritic cells were utilized as accessory cells in the primary cultures, but had minimal effect in the presence of B cells. @entity2 suppressed the generation of @entity1 -producing cells, presumably by inhibiting their expansion following primary activation. Finally, in vitro-generated @entity1 -producing T cells were the most potent helpers for B lymphocytes. Thus, exogenous cytokines alter the patterns of T-cell differentiation in vitro, and the effects of cytokines vary depending on the types of accessory cells present during initial T-cell activation.

title: Differentiation of V beta 8.2+ CD4+ T cells induced by a superantigen: roles of XXXX and cytokines.

answer: @entity3


abstract: BACKGROUND: "Inappropriate" @entity8 (IST) is an uncommon and poorly defined @entity3 characterized by inappropriate @entity3 and exaggerated acceleration of heart rate with "normal" P wave. The mechanism of this @entity3 is unknown. The purpose of the present study was to determine the role of autonomic balance in the genesis of IST. METHODS AND RESULTS: Six female @entity0 aged 23 to 38 years with IST and 10 age- and sex-matched control subjects were assessed with the following autonomic function tests: (1) sympathovagal balance to the sinus node assessed by calculating the LF/HF (low frequency/high frequency) ratio using power spectral analysis both in the supine position and after 10 minutes of head-up tilt to 60 degrees, (2) cardiovagal reflex assessed by cold face test (CFT), (3) beta-adrenergic sensitivity as determined by calculating @entity6 dose-response curves and @entity6 chronotropic dose 25 (CD25), and (4) intrinsic heart rate (IHR) assessed after autonomic blockade with @entity7 0.04 mg/kg and @entity4 0.2 mg/kg administered as an intravenous bolus. No significant differences in the LF/HF ratio both in the supine position (2.8 +/- 0.3 versus 2.6 +/- 0.4) and during upright tilt (8.7 +/- 1.3 versus 8.5 +/- 0.5) were observed between control subjects and IST @entity0 . Cardiovagal response to CFT was markedly @entity2 in all @entity0 (6.3% IST @entity0 versus 24.2% control subjects, P < .001). beta-Adrenergic @entity1 to @entity6 was noted in all @entity0 (mean CD25, 0.29 +/- 0.10 microgram IST @entity0 versus 1.27 +/- 0.4 microgram control subjects; P < .001), and high IHR was noted in all cases. The @entity0 were treated with high doses of beta-blockers with adequate short-term control. Radiofrequency catheter ablation of the sinus node area was performed in one drug-refractory @entity0 . CONCLUSIONS: These findings suggest that the mechanism leading to IST is related to a primary @entity5 characterized by a high IHR, @entity2 efferent cardiovagal reflex, and beta-adrenergic @entity1 .

title: XXXX . Role of sympathovagal balance.

answer: @entity8


abstract: Angiogenesis is a process fundamental to the growth of many solid @entity1 . Agents that inhibit angiogenesis may have a role in preventing @entity1 growth. @entity6 , a synthetic analogue of @entity7 , has been shown to inhibit @entity1 growth in several extracranial @entity1 models. Its use has been reported to have minimal side effects. No studies have been reported using @entity6 in the treatment of an @entity1 . To determine the effect of @entity6 on an @entity1 , we used an improved implantation technique to place 80,000 9L @entity1 cells into the right caudate nucleus of 25 male Fischer 344 @entity2 . Starting on the first post-implantation day, 12 animals received 30 mg kg-1 @entity6 via intraperitoneal injection every other day until @entity3 . Thirteen control animals received vehicle only. Evidence of @entity1 was apparent in 22/23 animals (96%). All animals treated with @entity6 experienced a progressive and significant @entity4 when compared to controls. At day 17, treated animals retained 80.0 +/- 2.2% of their initial weight, (mean +/- SD) compared to 100.9 +/- 3.6% for controls (p = 2.25 x 10(-12); student's t-test). @entity6 had no effect on survival. Median survival in the treatment group was 24.5 days compared to 25 days in the controls (p = 0.95; Mann-Whitney). @entity6 , although promising in @entity1 models, may not be as effective in controlling the growth of @entity1 , and its use is not without significant systemic effects. More studies are needed before this drug is used in @entity0 @entity5 trials.(ABSTRACT TRUNCATED AT 250 WORDS)

title: The effect of XXXX in an improved intracranial 9L gliosarcoma @entity2 model.

answer: @entity6


abstract: Angiogenesis is a process fundamental to the growth of many solid @entity1 . Agents that inhibit angiogenesis may have a role in preventing @entity1 growth. @entity6 , a synthetic analogue of @entity7 , has been shown to inhibit @entity1 growth in several extracranial @entity1 models. Its use has been reported to have minimal side effects. No studies have been reported using @entity6 in the treatment of an @entity1 . To determine the effect of @entity6 on an @entity1 , we used an improved implantation technique to place 80,000 9L @entity1 cells into the right caudate nucleus of 25 male Fischer 344 @entity2 . Starting on the first post-implantation day, 12 animals received 30 mg kg-1 @entity6 via intraperitoneal injection every other day until @entity3 . Thirteen control animals received vehicle only. Evidence of @entity1 was apparent in 22/23 animals (96%). All animals treated with @entity6 experienced a progressive and significant @entity4 when compared to controls. At day 17, treated animals retained 80.0 +/- 2.2% of their initial weight, (mean +/- SD) compared to 100.9 +/- 3.6% for controls (p = 2.25 x 10(-12); student's t-test). @entity6 had no effect on survival. Median survival in the treatment group was 24.5 days compared to 25 days in the controls (p = 0.95; Mann-Whitney). @entity6 , although promising in @entity1 models, may not be as effective in controlling the growth of @entity1 , and its use is not without significant systemic effects. More studies are needed before this drug is used in @entity0 @entity5 trials.(ABSTRACT TRUNCATED AT 250 WORDS)

title: The effect of @entity6 in an improved intracranial 9L gliosarcoma XXXX model.

answer: @entity2


abstract: Based on the experience in a psychosomatic clinic, @entity3 among @entity4 @entity0 are reported. The following three theses have evolved: 1. By far most important of all is the problem of tranquilizer abuse, which entails serious, and sometimes dramatic, @entity5 . An indication for continuous tranquilizer medication does not exist. 2. Compound preparations are problematical, in particular if they contain codeine. We frequently see abuse and even dependence. 3. Opium derivatives continue to be rarely prescribed in non- @entity1 @entity4 . Several instances of incorrect @entity2 management have been found, such as prescription to substance abusers, on insufficient indication, or prescription on request instead of time-schedule therapy.

title: [Problems of XXXX medication and dependence].

answer: @entity2


abstract: @entity1 is generally managed with bronchodilator therapy and/or anti-inflammatory drugs. Guidelines now advocate selection of drugs and pharmaceutical formulations (long-acting vs short-acting, inhaled vs systemic) on the basis of disease severity. Theophylline has a narrow therapeutic margin. Clearance is highly variable and plasma concentrations should be monitored to avoid the occurrence of plasma concentration-related adverse effects. The rate of absorption of @entity4 differs depending on the sustained release formulation administered. Some products do not provide sufficient plasma drug concentrations for therapeutic efficacy over a 12-hour period, particularly in @entity0 with high clearance rates (e.g. @entity0 and @entity0 who smoke). Administration of drugs via inhalation offers several advantages over systemic routes of administration (e.g. adverse effects are decreased). Inhalation is now advocated as first-line therapy. Aerosol medications available for the treatment of @entity1 are @entity3 -agonist (including the newer long-acting agents such as @entity6 ), corticosteroids, anticholinergic drugs, @entity5 (cromolyn @entity2 ) and nedocromil. To reach the airways, aerosolised particles should be 1 to 5 microns in diameter. Particles of this size can be produced by nebuliser for continuous administration or by metered-dose inhaler and drug powder inhaler for unit dose medication. For efficient use of the metered-dose inhaler, slow inhalation and actuation must be coordinated. However, efficacy and convenience can be improved when spacer devices are used. Furthermore, spacer devices lessen the oropharyngeal adverse effects of inhaled corticosteroids. Dry powder inhalers are more easily used by @entity0 and elderly @entity0 than metered-dose inhalers. Regardless of the device used, a maximum of 10% of the inhaled dose reaches the airways. The rest of the dose is swallowed and absorbed through the gastrointestinal tract. Most inhaled drugs have low oral bioavailability, either because of a high first-pass metabolism ( @entity3 -agonists and glucocorticoids) or because of lack of absorption ( @entity5 ). Sulphation of @entity3 -agonists occurs in the wall of the gastrointestinal tract and extensive metabolism of inhaled corticosteroids occurs in the liver. Low bioavailability of the swallowed fraction contributes to reduced adverse effects. The pharmacokinetic properties of an inhaled drug are of interest. The fraction of the dose absorbed through the lung has the same disposition characteristics as an intravenous dose, and the swallowed fraction has the same disposition as an orally administered dose. However, for many drugs, pharmacokinetic data after inhalation are limited and cannot be used as a criteria for selection of therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

title: Pharmacokinetic optimisation of XXXX treatment.

answer: @entity1


abstract: Schmallenberg virus (SBV) is an Orthobunyavirus that induces abortion, @entity3 and @entity0 in ruminants. @entity2 induces a long lasting seroconversion under natural conditions. The persistence of the protective immunity and the isotype specific antibody response upon @entity2 of @entity1 has however not been studied in detail. Five @entity1 were kept in BSL3 facilities for more than 16  months and subjected to repeated @entity2 . Blood was regularly sampled and organs were collected at euthanasia. The presence of SBV RNA in serum and organs was measured with quantitative real-time PCR. The appearance and persistence of neutralizing and SBV nucleoprotein (N) isotype specific antibodies was determined with virus neutralization tests (VNT) and ELISAs. The primo @entity2 protected ewes against clinical signs, viraemia and virus replication in organs upon challenge infections more than 15  months later. Production of neutralizing SBV specific antibodies was first detected around 6  days post primo-inoculation with VNT and correlated with the appearance of SBV-N specific IgM antibodies. These IgM antibodies remained present for 2  weeks. SBV-N specific IgG antibodies were first detected between 10 and 21 dpi and reached a plateau at 28 dpi. This plateau remained consistently high and no significant decrease in titre was found over a period of more than 1  year. Similar results were found for the neutralising antibody response. In conclusion, the SBV specific IgM response probably eliminates SBV from the blood and the protective immunity induced by @entity2 protects @entity1 against reinfection for at least 16  months.

title: Persistence of the protective immunity and kinetics of the isotype specific antibody response against the viral nucleocapsid protein after experimental Schmallenberg virus infection of XXXX .

answer: @entity1


abstract: BACKGROUND: Previous reports about laparoscopic total pelvic exenteration (LTPE) are still limited. In the present study, we described our single-center experience of the initial 11 cases. METHODS: Between April 2011 and September 2015, eight males and three females diagnosed as @entity2 underwent LTPE by the same operation team. We retrospectively collected all cases' parameters about surgical technique. Thirty-seven @entity0 who received open surgery were also retrospectively collected. A comparison between LTPE and open surgery was performed to evaluate the feasibility and safety of LTPE. RESULTS: Eleven cases successfully underwent the LTPE without any @entity5 . No open conversion was required. Eight @entity0 underwent Bricker's procedure. Three @entity0 were performed with the cutaneous ureterostomy. Anus preservation operation was performed in three @entity0 . Compared with open surgery, LTPE had longer mean operative time (565.2 vs 468.2  min, p   =   0.004) but less mean @entity3 (547.3 vs 1033.0  ml, p   <   0.001) and shorter postoperative hospitalization time (15.3 vs 22.4  days, p   =   0.004). One @entity0 died of @entity4 in the 7th month of follow-up time. One @entity0 died of recurrence in the 12th month of follow-up time. Nine @entity0 are still alive without recurrence and @entity1 . The mean follow-up time was 11.1  months. CONCLUSIONS: The technique of LTPE seems to be feasible and safe in the treatment of carefully selected @entity0 of @entity2 . LTPE can also decrease the @entity3 , the recovery time, and the hospital stay. But the oncological safety and long-term outcome of LTPE still need to be explored.

title: Laparoscopic total pelvic exenteration for XXXX : the technique and short-time outcome of 11 cases.

answer: @entity2


abstract: We have cultured transverse slices of the hippocampal formation from neonatal @entity0 and have identified the cell types which appear in the outgrowth with cell type specific markers. @entity1 toxin and anti- @entity1 toxoid, as well as antisera to neurofilaments and 14-3-2 protein, were used to identify neurons. Astrocytes were identified with antisera to glial fibrillary acidic protein and were the predominant non-neural cell type. Fibroblastic cells were labeled with antisera to fibronectin and to myosin and oligodendroglia were identified with antisera to @entity3 . The hippocampal neurons could be classified as 1 or the 3 types present in vivo (pyramidal cells, granule cells, or GABAergic interneurons) on the basis of their size, shape, location, or reaction with antisera to @entity2 decarboxylase. Outgrowth of glial cells and neurites occurred within hours of explantation. Within a few days granule cell neurons migrated onto the glial cell layer from the explant. Their movement is probably related to their migration during in vivo development of the granule cell layer. Synapse formation was observed by electron microscopic analysis beginning about 3-5 days in vitro and areas of neuropil containing many synapses were observed after 3-4 weeks. This culture system should be useful for further studies on the cellular processes which occur during hippocampal development and plasticity.

title: Identification of cell types in XXXX hippocampal slices maintained in organotypic cultures.

answer: @entity0


abstract: Distribution of @entity4 and @entity1 was studied by immunohistochemistry in intraepithelial squamous cell lesions of @entity0 bronchus. Ten biopsy specimens were examined for each of the following categories of lesions (50 specimens altogether): normal bronchial epithelium, @entity5 , @entity5 , and @entity2 in situ, in addition to invasive @entity2 . The percentage positivity of immunoreactive cells and their localization in the epithelium were examined in formalin-fixed, @entity3 -embedded tissues of bronchial biopsy specimens retrieved from the surgical pathology file. @entity4 positivity ranged from 3.2% (normal bronchial epithelium), to 7.6% ( @entity5 ), 51.8% ( @entity5 ), and 85.0% ( @entity2 in situ). The difference between the groups was statistically significant (p < 0.01). The percentage positivity for invasive @entity2 was 56.9%. @entity1 positivity ranged from 7.3% (normal bronchial epithelium), to 38.7% (benign squamous epithelium), 67.5% ( @entity5 ), and 91.3% ( @entity2 in situ). The difference between the groups was statistically significant (p < 0.01). Invasive @entity2 positivity was 49.7%. Both @entity4 -positive and @entity1 -positive cells showed zonal distribution in the bronchial epithelium. They were located in the basal cell layer in normal bronchial epithelium and expanded upward as the morphologic changes advanced. In @entity2 in situ, both @entity4 -positive and @entity1 -positive cells covered the entire thickness of the bronchial epithelial layer.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Distribution of @entity4 and XXXX in intraepithelial squamous cell lesions of @entity0 bronchus.

answer: @entity1


abstract: Distribution of @entity4 and @entity1 was studied by immunohistochemistry in intraepithelial squamous cell lesions of @entity0 bronchus. Ten biopsy specimens were examined for each of the following categories of lesions (50 specimens altogether): normal bronchial epithelium, @entity5 , @entity5 , and @entity2 in situ, in addition to invasive @entity2 . The percentage positivity of immunoreactive cells and their localization in the epithelium were examined in formalin-fixed, @entity3 -embedded tissues of bronchial biopsy specimens retrieved from the surgical pathology file. @entity4 positivity ranged from 3.2% (normal bronchial epithelium), to 7.6% ( @entity5 ), 51.8% ( @entity5 ), and 85.0% ( @entity2 in situ). The difference between the groups was statistically significant (p < 0.01). The percentage positivity for invasive @entity2 was 56.9%. @entity1 positivity ranged from 7.3% (normal bronchial epithelium), to 38.7% (benign squamous epithelium), 67.5% ( @entity5 ), and 91.3% ( @entity2 in situ). The difference between the groups was statistically significant (p < 0.01). Invasive @entity2 positivity was 49.7%. Both @entity4 -positive and @entity1 -positive cells showed zonal distribution in the bronchial epithelium. They were located in the basal cell layer in normal bronchial epithelium and expanded upward as the morphologic changes advanced. In @entity2 in situ, both @entity4 -positive and @entity1 -positive cells covered the entire thickness of the bronchial epithelial layer.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Distribution of XXXX and @entity1 in intraepithelial squamous cell lesions of @entity0 bronchus.

answer: @entity4


abstract: Distribution of @entity4 and @entity1 was studied by immunohistochemistry in intraepithelial squamous cell lesions of @entity0 bronchus. Ten biopsy specimens were examined for each of the following categories of lesions (50 specimens altogether): normal bronchial epithelium, @entity5 , @entity5 , and @entity2 in situ, in addition to invasive @entity2 . The percentage positivity of immunoreactive cells and their localization in the epithelium were examined in formalin-fixed, @entity3 -embedded tissues of bronchial biopsy specimens retrieved from the surgical pathology file. @entity4 positivity ranged from 3.2% (normal bronchial epithelium), to 7.6% ( @entity5 ), 51.8% ( @entity5 ), and 85.0% ( @entity2 in situ). The difference between the groups was statistically significant (p < 0.01). The percentage positivity for invasive @entity2 was 56.9%. @entity1 positivity ranged from 7.3% (normal bronchial epithelium), to 38.7% (benign squamous epithelium), 67.5% ( @entity5 ), and 91.3% ( @entity2 in situ). The difference between the groups was statistically significant (p < 0.01). Invasive @entity2 positivity was 49.7%. Both @entity4 -positive and @entity1 -positive cells showed zonal distribution in the bronchial epithelium. They were located in the basal cell layer in normal bronchial epithelium and expanded upward as the morphologic changes advanced. In @entity2 in situ, both @entity4 -positive and @entity1 -positive cells covered the entire thickness of the bronchial epithelial layer.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Distribution of @entity4 and @entity1 in intraepithelial squamous cell lesions of XXXX bronchus.

answer: @entity0


abstract: Recent studies revealed that several vibrio species have evolved the capacity to survive inside host cells. However, it is still often ignored if intracellular stages are required for pathogenicity. Virulence of @entity3 , a strain pathogenic for @entity2 oysters, depends on entry into hemocytes, the oyster immune cells. We investigated here the mechanisms of @entity3 intracellular survival and their consequences on the host-pathogen interaction. Entry and survival inside hemocytes were required for @entity3 -driven cytolysis of hemocytes, both in vivo and in vitro. @entity3 intracellular stages showed a profound boost in metabolic activity and a major transcription of antioxidant and @entity1 detoxification genes, as revealed by RNA sequencing. @entity3 isogenic mutants showed that resistance to oxidative stress and @entity1 efflux are two main functions required for vibrio intracellular stages and @entity0 to hemocytes. @entity1 efflux was also essential for host colonization and virulence in vivo. Altogether, our results identify @entity1 resistance as a major mechanism to resist killing by phagocytes, induce cytolysis of immune cells and colonize oysters. Selection of such resistance traits could arise from vibrio interactions with @entity1 -rich environmental niches including marine invertebrates, which favour the emergence of pathogenic vibrios resistant to intraphagosomal killing across animal species.

title: XXXX homeostasis at the host vibrio interface: lessons from intracellular vibrio transcriptomics.

answer: @entity1


abstract: UNASSIGNED: The frictional response of whole @entity0 joints over durations spanning activities of daily living has not been reported previously. This study measured the friction of @entity0 @entity3 during 24h of reciprocal loading in a pendulum testing device, at moderate (0.2mm/s, 4320 cycles) and low (0.02mm/s, 432 cycles) sliding speeds, under a 200N load. The effect of joint congruence was also investigated by testing @entity0 humeral heads against significantly larger mature @entity2 glenoids. Eight @entity0 joints and six @entity2 joints were tested in four combinations: @entity0 joints tested at moderate (hHCMS, n=6) and low speed (hHCLS, n=3), @entity0 humeral heads tested against @entity2 glenoids at moderate speed (LCMS, n=3), and @entity2 joints tested at moderate speed (bHCMS, n=3). In the first half hour the mean  standard deviation of the friction coefficient was hHCMS: 0.0016  0.0011, hHCLS: 0.0012  0.0002, LCMS: 0.0008  0.0002 and bHCMS: 0.0024  0.0008; in the last four hours it was hHCMS: 0.0057  0.0025, hHCLS: 0.0047  0.0017, LCMS: 0.0012  0.0003 and bHCMS: 0.0056  0.0016. The initial value was lower than the final value (p<0.0001). The value in LCMS was significantly lower than in hHCMS and bHCMS (p<0.01). No @entity1 was observed in any of the specimens. These are the first results to demonstrate that the friction coefficient of natural @entity0 shoulders remains remarkably low (averaging as little as 0.0015 and no greater than 0.006) for up to 24h of continuous loading. The sustained low friction coefficients observed in @entity3 rolling rather than sliding friction.

title: The friction coefficient of XXXX remains remarkably low over 24h of loading.

answer: @entity3


abstract: Twelve @entity2 undergoing coronary artery bypass grafting had the Hemopump to decompress the heart and as circulatory support. The @entity2 also were given a short-acting beta-blocker, @entity3 , to make the heart flaccid. Extracorporeal circulation was not used. During Hemopump support, a bolus dose of 0.5 to 5 mg/kg of @entity3 was given before incremental titration steps from 100 to 600 micrograms.kg-1.min-1 over 15 to 20 minutes. The internal thoracic artery was sutured to the distal part of the left anterior descending artery. The Hemopump was withdrawn to the aorta after a weaning period of 20 to 30 minutes. Seven of 12 @entity2 went through the whole procedure and the Hemopump was weaned off without complications. Five animals died due to @entity1 in association with @entity3 administration. There was a big interindividual difference in @entity3 dose-response curves in the surviving animals. No significant differences in the hemodynamic variables were observed during the experiment. The Hemopump in combination with a short-acting beta-blocker could be an alternate way of performing coronary artery bypass grafting in selected @entity0 .

title: Coronary artery operation supported by the Hemopump: an experimental study on XXXX .

answer: @entity2


abstract: @entity6 following focal @entity10 is widely attributed to the excitotoxic effects of @entity8 . However, critical analysis of published data on @entity8 @entity2 in vitro and the comparison of these data with in vivo release of @entity8 and the therapeutic effect of @entity8 antagonists raises doubts about a @entity9 mechanism. An alternative explanation for @entity8 -mediated injury is @entity5 due to peri- @entity7 spreading @entity4 -like depolarizations. These depolarizations are triggered in the core of the @entity7 and spread at irregular intervals into the peri- @entity7 surrounding. In ischemically uncompromised tissue, the metabolic workload associated with spreading @entity4 is coupled to an increase in blood flow and @entity0 supply, assuring maintenance of oxidative respiration. In the penumbra region of focal @entity1 , the hemodynamic constraints of collateral blood circulation prevail the adequate adjustment of @entity0 delivery, leading to transient episodes of relative tissue @entity5 . The @entity5 episodes cause a suppression of protein synthesis, a gradual deterioration of energy metabolism and a progression of irreversibly damaged tissue into the penumbra zone. The generation of peri- @entity7 spreading @entity4 and the associated metabolic workload can be suppressed by @entity3 and non- @entity3 antagonists. As a result, the penumbral inhibition of protein synthesis and the progressing energy failure is also prevented, and the volume of @entity7 decreases. Interventions to improve ischemic resistance should therefore aim at improving the @entity0 supply or reducing the metabolic workload in the penumbra region.

title: XXXX -mediated injury in focal @entity10 : the excitotoxin hypothesis revised.

answer: @entity8