abstract: @entity1148 in the course of @entity102 like @entity4018 ( @entity4018 ) and of course essential @entity1148 (ET), are characterized by life-threatening complications. In a number of clinical trials the recently introduced drug Agrylin((R)) has proven to be very effective. The normalization of the platelet count was related to an interference with megakaryocyte maturation leading to a left-shifting of this cell lineage and/or a reduced proliferation. However, until now no systematic study has been performed on the relationship between development of megakaryopoiesis and proliferative activity. In this investigation we included 10 @entity1 with @entity4018 and 5 @entity1 with ET that had received Agrylin((R)) for a period ranging between 6 and 70 months. Following therapy this cohort revealed a decrease in the platelet count from 1,104x10(9)/l at diagnosis to 485x10(9)/l. In this context we focused on an immunohistochemical and morphometric analysis of the @entity1428 (+) megakaryopoiesis involving also endomitotic reduplication, by applying a double-immune incubation technique with the @entity1364 ( @entity1364 ). Moreover, we determined the changes of fiber density during observation time. According to our results, the @entity882 effect of Agrylin((R)) is based on an arrest in the dynamics of megakaryocyte maturation towards large (mature) platelet-shedding (polyploid) cells. This pathomechanism causes a significant increase in the number of promegakaryoblasts and megakaryoblasts. On the other hand, the total amount of @entity1428 (+) megakaryocytic cells is not increased. Related to the peculiar cell biology of endomitotic reduplication during the maturation process and its different periods alloted to each single step, @entity1364 activity (late G1- and S-phase of the cell cycle) is found to be enhanced in the megakaryocyte precursors. Finally, no significant influence of Agrylin((R)) on the evolution of @entity4018 is detectable and there is a general improvement of hematological data especially in @entity4018 .

title: [Anagrelide-induced changes of megakaryopoiesis during therapy of @entity102 with XXXX ].

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

entities_list: @entity1148 :: ('MESH:D013922', 'Disease') :: ['thrombocythemia', 'Thrombocythemia']

entities_list: @entity1364 :: ('5111', 'Gene') :: ['proliferating cell nuclear antigen', 'PCNA']

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

entities_list: @entity102 :: ('MESH:D002908', 'Disease') :: ['chronic myeloproliferative disorders']

entities_list: @entity4018 :: ('MESH:D055728', 'Disease') :: ['cIMF', 'myelofibrosis', 'chronic idiopathic myelofibrosis']

answer: @entity1148 :: (MESH:D013922,Disease) :: ['thrombocythemia']


abstract: @entity1148 in the course of @entity102 like @entity4018 ( @entity4018 ) and of course essential @entity1148 (ET), are characterized by life-threatening complications. In a number of clinical trials the recently introduced drug Agrylin((R)) has proven to be very effective. The normalization of the platelet count was related to an interference with megakaryocyte maturation leading to a left-shifting of this cell lineage and/or a reduced proliferation. However, until now no systematic study has been performed on the relationship between development of megakaryopoiesis and proliferative activity. In this investigation we included 10 @entity1 with @entity4018 and 5 @entity1 with ET that had received Agrylin((R)) for a period ranging between 6 and 70 months. Following therapy this cohort revealed a decrease in the platelet count from 1,104x10(9)/l at diagnosis to 485x10(9)/l. In this context we focused on an immunohistochemical and morphometric analysis of the @entity1428 (+) megakaryopoiesis involving also endomitotic reduplication, by applying a double-immune incubation technique with the @entity1364 ( @entity1364 ). Moreover, we determined the changes of fiber density during observation time. According to our results, the @entity882 effect of Agrylin((R)) is based on an arrest in the dynamics of megakaryocyte maturation towards large (mature) platelet-shedding (polyploid) cells. This pathomechanism causes a significant increase in the number of promegakaryoblasts and megakaryoblasts. On the other hand, the total amount of @entity1428 (+) megakaryocytic cells is not increased. Related to the peculiar cell biology of endomitotic reduplication during the maturation process and its different periods alloted to each single step, @entity1364 activity (late G1- and S-phase of the cell cycle) is found to be enhanced in the megakaryocyte precursors. Finally, no significant influence of Agrylin((R)) on the evolution of @entity4018 is detectable and there is a general improvement of hematological data especially in @entity4018 .

title: [Anagrelide-induced changes of megakaryopoiesis during therapy of XXXX with @entity1148 ].

answer: @entity102 :: (MESH:D002908,Disease) :: ['chronic myeloproliferative disorders']


abstract: INTRODUCTION AND DEVELOPMENT: During episodes of @entity63 / @entity519 , the neurochemical and environmental changes considered toxic for nervous tissue lie behind the characteristic abrupt @entity1358 ( @entity1358 ). A strong resemblance with other pathologic events enable us to postulate that @entity1358 is a different state of the tissue that includes among others the anoxic depolarization and Le o s spreading @entity308 . @entity1358 is an active event. Neurons enter and leave @entity1358 suddenly and synchronously, and contrary to current belief, their membrane integrity is preserved and ion gradients are only reduced. Biophysical membrane properties are not compatible with some postulates based on endotoxines. There is a direct relation between @entity1358 susceptibility of the different neuron types/nuclei and their vulnerability to @entity63 / @entity519 . Two different substates can be distinguished in the associated interstitial potentials that are likely related to @entity66 , respectively. The different modes and timings of anoxic @entity528 depend on the duration of @entity1358 , the functional integrity of the glial network, and the history of previous insults. CONCLUSIONS: @entity1358 is a cellular state of risk bridging life and @entity204 . Neurons die if they cannot exit, but may recover if they do promptly, although still have to face subtle changes as well initiated during @entity1358 that will eventually lead them to a delayed @entity204 . Avoiding @entity1358 is escaping @entity204 . From a clinical point of view, the relevant point is that manipulating @entity1358 entails the simultaneous control of all toxic neurochemical concomitants. Reinforcing vulnerable neurons to avoid their falling into @entity1358 is possible

title: [Tracking along the path toward ischemic XXXX ].

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

entities_list: @entity66 :: ('MESH:D004194', 'Disease') :: ['neuronal and glial dysfunction']

entities_list: @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia']

entities_list: @entity1358 :: ('MESH:D002292', 'Disease') :: ['massive cell depolarization', 'MCD']

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

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


abstract: OBJECTIVES: To present 4 @entity1 with @entity14475 who had a favourable evolution as well as to show that many cases have better prognosis than it is usually though. CASE REPORT: Anamnesis, image and psychological studies of 4 @entity1 with @entity14475 , who had been seen in the Pediatric Neurology Service of the University Hospital La Paz of Madrid. RESULTS: Four of our 11 @entity1 with @entity14475 (36.36%) presented a favourable evolution. Their age ranged between 25 months old and 12 years old. The comprehensive language corresponded to their ages in 3 @entity1 . Two @entity1 began to talk at 19 and 20 months respectively. Three @entity1 exhibited a normal language and 1 only communicated by gestures at the time of the last clinical study. All the four @entity1 walked without help. The mental level was calculated by the Raven scale in 2 cases and they showed a borderline intellectual quotient (IQ). Both @entity1 were self sufficient in their daily cleanliness and feeding. A @entity1 was able to read, to write and to make mathematical calculi. CONCLUSIONS: The @entity14475 is a heterogeneous disease from the clinic and genetics points of view, as well as in the evolution. Because of that, an attentive neuropsychological evaluation is necessary before giving the prognosis of the @entity1 .

title: [ XXXX . Report of four cases with a favourable evolution].

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

entities_list: @entity14475 :: ('MESH:C536293', 'Disease') :: ['Joubert syndrome']

answer: @entity14475 :: (MESH:C536293,Disease) :: ['Joubert syndrome']


abstract: A locus containing two hsp16 genes in @entity2199 has been characterized by DNA sequencing. Each gene encodes a 16-kDa polypeptide which is expressed following heat induction. The two genes, designated @entity16473 and @entity27766 , are arranged in divergent orientations, and each contains a single intron of 46 and 58 base pairs, respectively. Although both gene transcripts are spliced efficiently in vivo, @entity27766 corresponds to a previously isolated cDNA which contains an unspliced intron sequence. The 5'-noncoding regions of both genes contain TATA boxes preceded 18 or 19 @entity2036 upstream by a @entity1457 regulatory sequence. The 3'-noncoding regions contain polyadenylation signals (AATAAA) either downstream ( @entity16473 ) or immediately adjacent ( @entity27766 ) to a sequence capable of forming a hairpin. This pair of hsp16 genes is flanked by three copies of an approximately 200-bp dispersed repetitive element (two copies on one side and a single one on the other side of the locus) which occurs in at least 70 copies throughout the @entity2199 genome, and has been designated CeRep-16. Together with data described previously (Russnak, R. H., and Candido, E. P. M. (1985) Mol. Cell. Biol. 5, 1268-1278), the results presented here define a family of four distinct, related small @entity1457 protein genes. These are arranged in divergently transcribed pairs at two loci. The @entity27765 /41 genes code for one class of HSP16, 143- @entity535 residues long, while the @entity71001 genes encode the other class, which is 2 @entity535 residues longer. Thus each locus codes for the two major types of HSP16. The two loci differ in a number of respects, including the presence of a tandem inverted duplication of two @entity1457 protein genes at one locus, and of repetitive elements at the other. Sequence comparisons allow us to propose a scheme for the evolution of the four genes and reveal conserved features of noncoding regions which may be involved in the regulation of their transcription, RNA processing, or translation. Using locus-specific hybridization probes, we have found that the genes at locus @entity16473 /41 are expressed at levels approximately 20-40-fold higher than those at locus @entity71002 .

title: Structure, expression, and evolution of a @entity1457 gene locus in XXXX that is flanked by repetitive elements.

entities_list: @entity2199 :: ('6239', 'Species') :: ['Caenorhabditis elegans', 'C. elegans']

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

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

entities_list: @entity1457 :: ('MESH:D012769', 'Disease') :: ['heat shock']

answer: @entity2199 :: (6239,Species) :: ['Caenorhabditis elegans']


abstract: A locus containing two hsp16 genes in @entity2199 has been characterized by DNA sequencing. Each gene encodes a 16-kDa polypeptide which is expressed following heat induction. The two genes, designated @entity16473 and @entity27766 , are arranged in divergent orientations, and each contains a single intron of 46 and 58 base pairs, respectively. Although both gene transcripts are spliced efficiently in vivo, @entity27766 corresponds to a previously isolated cDNA which contains an unspliced intron sequence. The 5'-noncoding regions of both genes contain TATA boxes preceded 18 or 19 @entity2036 upstream by a @entity1457 regulatory sequence. The 3'-noncoding regions contain polyadenylation signals (AATAAA) either downstream ( @entity16473 ) or immediately adjacent ( @entity27766 ) to a sequence capable of forming a hairpin. This pair of hsp16 genes is flanked by three copies of an approximately 200-bp dispersed repetitive element (two copies on one side and a single one on the other side of the locus) which occurs in at least 70 copies throughout the @entity2199 genome, and has been designated CeRep-16. Together with data described previously (Russnak, R. H., and Candido, E. P. M. (1985) Mol. Cell. Biol. 5, 1268-1278), the results presented here define a family of four distinct, related small @entity1457 protein genes. These are arranged in divergently transcribed pairs at two loci. The @entity27765 /41 genes code for one class of HSP16, 143- @entity535 residues long, while the @entity71001 genes encode the other class, which is 2 @entity535 residues longer. Thus each locus codes for the two major types of HSP16. The two loci differ in a number of respects, including the presence of a tandem inverted duplication of two @entity1457 protein genes at one locus, and of repetitive elements at the other. Sequence comparisons allow us to propose a scheme for the evolution of the four genes and reveal conserved features of noncoding regions which may be involved in the regulation of their transcription, RNA processing, or translation. Using locus-specific hybridization probes, we have found that the genes at locus @entity16473 /41 are expressed at levels approximately 20-40-fold higher than those at locus @entity71002 .

title: Structure, expression, and evolution of a XXXX gene locus in @entity2199 that is flanked by repetitive elements.

answer: @entity1457 :: (MESH:D012769,Disease) :: ['heat shock']


abstract: The gtfB gene coding for a glucosyltransferase (GTF) activity of @entity6586 GS-5 was isolated on a 15.4-kilobase DNA fragment by using a lambda L47.1 gene library. The activity was catalyzed by gene products of 150 and 145 kilodaltons which reacted with antibodies directed against both soluble and insoluble glucan-synthesizing GTFs. The enzyme present in crude @entity526 extracts synthesized both soluble and insoluble glucans. The enzyme was partially purified from lysates of the lambda DS-76 clone and synthesized both types of glucans in a primer-independent fashion. In addition, the purified enzyme exhibited a pI of approximately 5.0. Southern blot analysis indicated that the cloned GTF gene represented a contiguous @entity377 sequence on the strain GS-5 chromosome. Furthermore, evidence for the existence of a distinct gene sharing partial homology with gtfB was also obtained. The gtfB gene was subcloned into plasmid pACYC184 into @entity526 and exhibited GTF activity when carried on GS-5 inserts as small as 5 kilobases. The approximate location of the GTF promoter and the direction of gene transcription were also determined. The cloned enzyme was not secreted through the cytoplasmic membrane of @entity526 , since most of the activity was found in the cytoplasm and, in lesser amounts, associated with the cytoplasmic membrane. The gtfB gene was insertionally inactivated by introducing a gene fragment coding for @entity2929 resistance into the GTF coding region. After transformation of strain GS-5 with the altered gene, transformants defective in insoluble glucan synthesis were identified. These results indicate that the gtfB gene codes for a GTF involved in insoluble glucan synthesis in strain GS-5.

title: Cloning of a XXXX glucosyltransferase gene coding for insoluble glucan synthesis.

entities_list: @entity6586 :: ('1309', 'Species') :: ['Streptococcus mutans']

entities_list: @entity2929 :: ('MESH:D004917', 'Chemical') :: ['erythromycin']

entities_list: @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide']

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

answer: @entity6586 :: (1309,Species) :: ['Streptococcus mutans']


abstract: @entity460 -dependent protease II ( @entity13667 -II) from @entity291 heart is a heterodimer with subunit molecular weights of 80,000 and 26,000. Previous studies have demonstrated that the protease requires 350 microM @entity141 for half-maximal activity and that the large subunit contains both the catalytic and @entity141 binding functions of the enzyme. The function of the small subunit has been unclear. We have examined the effect of @entity141 on structural and catalytic properties of @entity13667 -II in the presence and absence of substrate proteins. When incubated with @entity141 in the absence of substrate, @entity13667 -II undergoes a series of autoproteolytic cleavages that sequentially reduce the small subunit's molecular weight from 26,000 to 24,000 to 22,000 to 17,000. During this time there is no detectable change in the 80-kDa subunit, which remains associated with the autolyzed small subunit. The rate of autoproteolysis is dependent on temperature and on the concentration of @entity141 (half-maximal rate at approximately 600 microM @entity141 ). The first cleavage appears to be unimolecular because its rate is unaffected by @entity13667 -II concentration or by the presence of exogenous protein substrates. Subsequent cleavages result in the formation of the 80-kDa/17-kDa heterodimer and appear to occur by bimolecular reactions; rates of these reactions were slowed by decreasing @entity13667 -II concentrations and by the presence of protein substrates. Autoproteolysis of the small subunit has two distinct functional consequences, each of which is associated with different forms of the autolyzed protease. Our results indicate that the 80-kDa/26-kDa form of @entity13667 -II represents an inactive proenzyme and that the initial @entity141 -dependent cleavage of the 26-kDa subunit results in activation of the protease. The activated enzyme hydrolyzes protein substrates with a @entity141 concentration requirement of 350 microM for half-maximal rates. The further autoproteolysis, which results in the formation of the 80-kDa/17-kDa heterodimer, serves to reduce the @entity141 concentration requirement for protease activity by 25-fold. Thus, these results provide evidence for specific roles of the small subunit in the regulation of @entity13667 -II activity.

title: Autoproteolysis of the small subunit of XXXX -dependent protease II activates and regulates protease activity.

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

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


abstract: Haeme metabolism remains a vulnerable problem for the intraerythrocytic @entity3964 which catabolises haemoglobin as a source of @entity1522 in an acidic, @entity26 -rich lysosome-like digestive vacuole. Haeme monomer, capable of generating @entity26 radicals, transforms into an inert crystal named malarial pigment or haemozoin by forming unique dimers that then crystalise. Laveran first described pigmented bodies in @entity1 to define a protozoan as the aetiologic agent of @entity311 . The trail of @entity311 pigment enabled Ross to implicate the mosquito in the life cycle of @entity3964 . In 1991, Slater and Cerami postulated a unique @entity68 - @entity3338 bond between two haemes in haemozoin crystals based on infrared and X-ray spectroscopy data. Additionally, parasite extracts were shown to possess a 'haeme polymerase' enzymatic activity as the process of crystal formation was then termed. Importantly, the @entity50125 , such as choloroquine, inhibit haemozoin formation. A @entity3964 derived @entity3793 -rich protein II, which binds haeme and initiates haemozoin formation, is present in the digestive vacuole. Pfhistidine-rich protein II and Pfhistidine-rich protein III are sufficient, but not necessary for haemozoin formation as a laboratory clone lacking both still makes the haeme crystals. The reduvid bug, and the Schistosoma and Haemoproteus genera also make haemozoin. Recently, Bohle and coworkers used X-ray diffraction to document the iron-carboxylate bond in intact desiccated parasites and to show that a Fe1-O41 head to tail haeme dimer is the unit building block of haemozoin. The role of the @entity3964 histidine-rich protein family members, lipids or potential novel proteins in the exact molecular assembly of the large molecular weight haeme crystals in the protein rich digestive vacuole needs to be solved. Accurate experimental determination of the role of haemozoin formation and inhibition as the target of @entity503 is fundamental to determination of the mechanism of @entity8774 drug action and resistance. The enhanced understanding of the biosynthetic pathway leading to haemozoin formation using functional proteomic tools and the mechanisms through which existing antimalarial drugs affect @entity3964 haeme chemistry will help design improved chaemotherapeutic agents.

title: Theories on malarial pigment formation and XXXX action.

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

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

entities_list: @entity8774 :: ('MESH:C037219', 'Chemical') :: ['quinoline']

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

entities_list: @entity50125 :: ('MESH:D011804', 'Chemical') :: ['quinolines']

entities_list: @entity3964 :: ('5833', 'Species') :: ['Plasmodium falciparum', 'Plasmodium']

entities_list: @entity503 :: ('MESH:D002738', 'Chemical') :: ['chloroquine']

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

answer: @entity8774 :: (MESH:C037219,Chemical) :: ['quinoline']


abstract: The aim of this study was to test the hypothesis that some of the proliferative effects of steroid hormones on @entity5 cells are mediated by the @entity8496 proto-oncogenes. The @entity1 @entity0 cell line MCF-7 is @entity1782 ( @entity1782 ) positive (+). NCI/ADR-RES is a @entity1 cell line lacking the @entity1782 ( @entity1782 -) that was initially named @entity33415 and @entity817 kinase activities were examined in cell lines treated with beta-estradiol for 24 hours. Increases in @entity10242 and @entity33415 activities were observed after treatment with beta-estradiol in the @entity1782 (+) MCF-7 cells but not in the @entity1782 (-) NCI/ADR-RES cells. In contrast, no significant changes in @entity817 activity were observed. Thus beta-estradiol can induce @entity10242 and @entity33415 activities in @entity1782 (+) cells. In addition, beta-estradiol caused cell cycle progression in MCF-7 cells and an increased proliferative response to beta-estradiol was observed in MCF-7, which overexpressed constitutively-active @entity10242 (MCF/DeltaRaf-1). Increased mRNA levels of the ligand for the @entity1722 receptor, @entity1915 (ARG) were observed after beta-estradiol treatment of MCF-7 cells whereas constitutively higher levels of ARG and its receptor, @entity1722 mRNAs were detected in MCF/DeltaRaf-1 cells. These findings suggest that targeting @entity8496 may prove efficacious in @entity0 therapies.

title: The effects of beta-estradiol on XXXX activity, cell cycle progression and growth factor synthesis in the @entity0 cell line.

entities_list: @entity1782 :: ('2099', 'Gene') :: ['ER', 'estrogen-receptor', 'estrogen receptor']

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

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

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


abstract: The aim of this study was to test the hypothesis that some of the proliferative effects of steroid hormones on @entity5 cells are mediated by the @entity8496 proto-oncogenes. The @entity1 @entity0 cell line MCF-7 is @entity1782 ( @entity1782 ) positive (+). NCI/ADR-RES is a @entity1 cell line lacking the @entity1782 ( @entity1782 -) that was initially named @entity33415 and @entity817 kinase activities were examined in cell lines treated with beta-estradiol for 24 hours. Increases in @entity10242 and @entity33415 activities were observed after treatment with beta-estradiol in the @entity1782 (+) MCF-7 cells but not in the @entity1782 (-) NCI/ADR-RES cells. In contrast, no significant changes in @entity817 activity were observed. Thus beta-estradiol can induce @entity10242 and @entity33415 activities in @entity1782 (+) cells. In addition, beta-estradiol caused cell cycle progression in MCF-7 cells and an increased proliferative response to beta-estradiol was observed in MCF-7, which overexpressed constitutively-active @entity10242 (MCF/DeltaRaf-1). Increased mRNA levels of the ligand for the @entity1722 receptor, @entity1915 (ARG) were observed after beta-estradiol treatment of MCF-7 cells whereas constitutively higher levels of ARG and its receptor, @entity1722 mRNAs were detected in MCF/DeltaRaf-1 cells. These findings suggest that targeting @entity8496 may prove efficacious in @entity0 therapies.

title: The effects of beta-estradiol on @entity8496 activity, cell cycle progression and growth factor synthesis in the XXXX cell line.

answer: @entity0 :: (MESH:D001943,Disease) :: ['MCF-7 breast cancer']


abstract: BACKGROUND/AIMS: To study the characteristics and outcome of @entity1 with @entity157 in a low-incidence region. METHODS: 98 @entity1 with @entity157 who had been referred to the Surgical Department, National Hospital, Oslo, between 1981 and 1999 were studied retrospectively. @entity5 size, prevalence of @entity82 , serum @entity160 concentration, rate of resection, type of resection and survival were analysed. RESULTS: 19% (19/98) of the @entity1 had @entity82 of varying aetiology. Median @entity5 size was 10 cm. @entity160 was normal in 46% of the @entity1 . Hepatic resection was performed in 30 (31%) @entity1 and 77% of the resections were major (more than 2 segments). Abdominal exploration was done in 33 @entity1 and liver transplantation in 6 @entity1 . No surgical intervention was made in 31 @entity1 . Five-year actuarial survival in resected @entity1 was 24%. Median survival of non-resected @entity1 was 3.3 months. CONCLUSION: The @entity1 characteristics in this study differ from @entity1 cohorts with @entity157 in other geographical areas. The main differences are large @entity5 size, low prevalence of the disease, and diverse aetiology of @entity82 .

title: XXXX in a low-incidence region. Surgical perspectives.

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

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

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

entities_list: @entity160 :: ('174', 'Gene') :: ['alpha-fetoprotein', 'alpha-Fetoprotein']

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

answer: @entity157 :: (MESH:D006528,Disease) :: ['Hepatocellular carcinoma']


abstract: BACKGROUND: Shock resuscitation is integral to early management of severely injured @entity1 . Our standardized shock resuscitation protocol, developed in 1997 and implemented as a computerized intensive care unit (ICU) bedside decision support tool in 2000, used @entity26 delivery index (Do I) > or = 600 mL/min/m as the intervention endpoint. In a recent publication, Shoemaker et al. refuted positive outcome effect of early supranormal Do (i.e., Do I > or = 600) resuscitation. In response to and because of ongoing concern for excessive volume loading, we decreased our Do I endpoint from 600 to 500. Our hypothesis was that by decreasing the Do I endpoint, less crystalloid would be administered. We compare resuscitation responses to the protocol with goals of Do I > or = 600 versus 500 in two @entity1 cohorts. METHODS: A standardized protocol was used to direct bedside decisions for resuscitation of @entity1 with @entity130 (Injury Severity Score > 15), @entity190 (> or = 6 units of packed red blood cells), metabolic stress (base deficit > or = 6 mEq/L), and no severe @entity1545 . The protocol logic is to attain and maintain Do I > or = a specified goal for the first 24 ICU hours using primarily blood and volume loading. Two cohorts were compared: Do I > or = 500 (18 @entity1 admitted February-August 2001) versus Do I > or = 600 (18 @entity1 admitted during 2000 age and gender matched with the Do I > or = 500 group). Data were analyzed using analysis of variance, chi, and t tests (p < 0.05). RESULTS: Both groups had similar demographics (age 30 +/- 3 years; 78% @entity1 ; Injury Severity Score 27 +/- 3), hemodynamics, and severity of shock at start of resuscitation in the ICU. Resuscitation response was Do I increase to > or = 600 for both cohorts within approximately 12 hours. Throughout the 24-hour ICU process, the Do I > or = 500 cohort received less lactated Ringer's volume than the Do I > or = 600 cohort (total of 8 +/- 1 vs. 12 +/- 2 L; p < 0.05) and tended to receive less blood transfusion (total of 3 +/- 1 vs. 5 +/- 1 units of packed red blood cells). CONCLUSION: Shock resuscitation using Do I > or = 500 was indistinguishable from Do I > or = 600 mL/min/m. Less volume loading was required to attain and maintain Do I > or = 500 than 600 using computerized protocol technology to standardize resuscitation during the first 24 ICU hours.

title: Normal versus supranormal XXXX delivery goals in shock resuscitation: the response is the same.

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

entities_list: @entity1545 :: ('MESH:D020214', 'Disease') :: ['brain injury']

entities_list: @entity190 :: ('MESH:D006473', 'Disease') :: ['blood loss']

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

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


abstract: @entity6196 of the posterior fossa/ @entity2946 ( @entity6196 ) are the most common malignant primary @entity1221 of childhood. Current approaches to therapy for @entity1 with @entity6196 are illustrative of both the advances which have been made in management of @entity1313 and the areas where increased understanding is needed. With the optimal use of surgery and radiotherapy, the majority of @entity1 with @entity6196 can be expected to be alive and free of disease 5 years after diagnosis. Based on various factors, including the age of @entity1 , the extent of the disease at the time of diagnosis and histological parameters, it is possible to stratify @entity1 with @entity6196 into 'risk' groups. It is unclear whether preoperative or postoperative factors are most predictive of outcome. @entity1 with factors predictive of a higher likelihood of disease relapse seem to benefit from treatment with chemotherapy. The amount of radiotherapy and the type and amount of chemotherapy which is most efficacious in controlling the disease has yet to be determined. @entity1 surviving @entity6196 are at high risk for endocrinologic and neuropsychologic sequelae. Multiple prospective treatment protocols are now underway, attempting to determine which therapy is best at controlling disease without causing severe long-term damage. A multidisciplinary approach is needed for the treatment of @entity1 with @entity6196 .

title: Management of @entity1 with primitive neuroectodermal tumors of the posterior fossa/ XXXX .

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

entities_list: @entity6196 :: ('MESH:D018242', 'Disease') :: ['PNET-MB', 'Primitive neuroectodermal tumors']

entities_list: @entity1313 :: ('MESH:D001932', 'Disease') :: ['childhood brain tumors']

entities_list: @entity1221 :: ('MESH:D016543', 'Disease') :: ['central nervous system tumors']

entities_list: @entity2946 :: ('MESH:D008527', 'Disease') :: ['medulloblastoma']

answer: @entity2946 :: (MESH:D008527,Disease) :: ['medulloblastoma']


abstract: @entity6196 of the posterior fossa/ @entity2946 ( @entity6196 ) are the most common malignant primary @entity1221 of childhood. Current approaches to therapy for @entity1 with @entity6196 are illustrative of both the advances which have been made in management of @entity1313 and the areas where increased understanding is needed. With the optimal use of surgery and radiotherapy, the majority of @entity1 with @entity6196 can be expected to be alive and free of disease 5 years after diagnosis. Based on various factors, including the age of @entity1 , the extent of the disease at the time of diagnosis and histological parameters, it is possible to stratify @entity1 with @entity6196 into 'risk' groups. It is unclear whether preoperative or postoperative factors are most predictive of outcome. @entity1 with factors predictive of a higher likelihood of disease relapse seem to benefit from treatment with chemotherapy. The amount of radiotherapy and the type and amount of chemotherapy which is most efficacious in controlling the disease has yet to be determined. @entity1 surviving @entity6196 are at high risk for endocrinologic and neuropsychologic sequelae. Multiple prospective treatment protocols are now underway, attempting to determine which therapy is best at controlling disease without causing severe long-term damage. A multidisciplinary approach is needed for the treatment of @entity1 with @entity6196 .

title: Management of XXXX with primitive neuroectodermal tumors of the posterior fossa/ @entity2946 .

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


abstract: BACKGROUND: Recently, detections of early @entity356 (EGC) have been increasing, and the treatment strategies for @entity356 have been changing. To demonstrate recent clinical experience of EGC in Japan and to assess modern strategies for the treatment of EGC, we investigated the English-language literature of the past 10 years through computer searches. METHODS: This article intends to provide gastric surgeons with recent Japanese experience of the treatment for EGC. In a search for modern treatments of EGC, we selected 100 papers published in well-known medical journals, and focused on the following items of EGC: (1) prognostic factors, (2) endoscopic treatment, (3) surgical procedures, and (4) Japanese guidelines. RESULTS: The most important factor influencing the survival of @entity1 with EGC is the status of lymph node @entity3 . The incidence of lymph node @entity3 is 1-3% for @entity1697 and 11-20% for @entity5 . Endoscopic mucosal resection (EMR) is a technique for the treatment of EGC, and the recent indication includes the @entity5 confined to the mucosa up to 3 cm in size or those invading the superficial submucosa. Surgical procedures include conventional Billroth I gastrectomy, limited resections, and laparoscopic surgery. Laparoscopic wedge resection using the lesion-lifting method and laparoscopy-assisted distal gastrectomy provide less @entity158 , faster recovery and shorter hospital stay. Guidelines for the treatment of @entity356 proposed by the Japanese @entity356 Association show that @entity1 with @entity1697 can be managed by EMR or distal gastrectomy, whereas @entity1 with @entity5 are candidates for distal gastrectomy with lymph node dissection. CONCLUSION: Although the prognosis of @entity1 with EGC depends on the presence or absence of lymph node @entity3 , most are successfully treated by modern endoscopic or surgical techniques. Laparoscopic surgery and limited resections will contribute to the better quality of life of @entity1 with EGC.

title: Modern treatment of early XXXX : review of the Japanese experience.

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

entities_list: @entity1697 :: ('MESH:D009062', 'Disease') :: ['mucosal cancer', 'mucosal cancers']

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

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

entities_list: @entity356 :: ('MESH:D013274', 'Disease') :: ['gastric cancer', 'Gastric Cancer']

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


abstract: STUDY DESIGN: A case of lower-extremity @entity602 induced by physical exertion in a @entity1 with Type 2 (failure of segmentation) @entity1513 is reported. OBJECTIVE: To describe the uncommon presentation of neurologic sequelae in a @entity1 with @entity1513 . SUMMARY OF BACKGROUND DATA: Various reports have described neurologic sequelae in @entity1 with Type 1 (failure of formation) @entity1513 . To the authors' knowledge, no case of @entity1513 leading to @entity16 has been reported. METHODS: A 17-year-old @entity1 presented with a 3-year history of progressively worsening @entity615 . During exertion, numbness developed along the posterior aspects of his legs, and he experienced a wobbly sensation in his lower extremities that prevented his participation in athletic activities. His static and dynamic neurologic examination was unremarkable. However, he developed a wide-based clumsy myelopathic gait when he was asked to run in the halls of the clinic. Magnetic resonance imaging demonstrated that the spinal cord was draped over the posterior vertebral body of T10. Anterior thoracic spinal cord decompression and fusion were performed through a seventh rib thoracotomy using a structural rib graft to fill the defect. The anterior 1 cm of bone was left intact so as not to cause any additional instability. RESULTS: The @entity1 tolerated the procedure well and had complete resolution of his exertionally dependent @entity1109 . At this writing, 3 years after surgery, he is involved in the Navy ROTC program. CONCLUSIONS: Although @entity1513 is a rare entity, it should be followed carefully and corrected surgically when appropriate. A history of exertional @entity602 may be an early sign of spinal cord impingement and is an indication for surgical decompression.

title: Exertional @entity602 in XXXX .

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

entities_list: @entity1513 :: ('MESH:D007738', 'Disease') :: ['Type 2 congenital kyphosis', 'congenital kyphosis']

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

entities_list: @entity16 :: ('MESH:D009422', 'Disease') :: ['neurologic symptoms']

entities_list: @entity1109 :: ('MESH:D012678', 'Disease') :: ['myelopathic symptoms']

entities_list: @entity615 :: ('MESH:D001416', 'Disease') :: ['midthoracic back pain']

answer: @entity1513 :: (MESH:D007738,Disease) :: ['type 2 congenital kyphosis']


abstract: STUDY DESIGN: A case of lower-extremity @entity602 induced by physical exertion in a @entity1 with Type 2 (failure of segmentation) @entity1513 is reported. OBJECTIVE: To describe the uncommon presentation of neurologic sequelae in a @entity1 with @entity1513 . SUMMARY OF BACKGROUND DATA: Various reports have described neurologic sequelae in @entity1 with Type 1 (failure of formation) @entity1513 . To the authors' knowledge, no case of @entity1513 leading to @entity16 has been reported. METHODS: A 17-year-old @entity1 presented with a 3-year history of progressively worsening @entity615 . During exertion, numbness developed along the posterior aspects of his legs, and he experienced a wobbly sensation in his lower extremities that prevented his participation in athletic activities. His static and dynamic neurologic examination was unremarkable. However, he developed a wide-based clumsy myelopathic gait when he was asked to run in the halls of the clinic. Magnetic resonance imaging demonstrated that the spinal cord was draped over the posterior vertebral body of T10. Anterior thoracic spinal cord decompression and fusion were performed through a seventh rib thoracotomy using a structural rib graft to fill the defect. The anterior 1 cm of bone was left intact so as not to cause any additional instability. RESULTS: The @entity1 tolerated the procedure well and had complete resolution of his exertionally dependent @entity1109 . At this writing, 3 years after surgery, he is involved in the Navy ROTC program. CONCLUSIONS: Although @entity1513 is a rare entity, it should be followed carefully and corrected surgically when appropriate. A history of exertional @entity602 may be an early sign of spinal cord impingement and is an indication for surgical decompression.

title: Exertional XXXX in @entity1513 .

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


abstract: The clinical efficacy of submucosal anal injections of @entity1499 in advanced @entity150 is investigated. An experimental study on 20 @entity19 has shown that @entity1499 injected into the anal submucosa has no clinicopathological effect on the anorectum. The clinical study comprised 18 @entity1 with advanced @entity150 (13 with stage T3 and 5 with stage T4 disease) as a test group in whom @entity1499 was injected into the anal submucosa and 8 (6 with stage T3 and 2 with stage T4 @entity5 ) treated concurrently with intravenous @entity1499 . The dose in both groups was 50 mg. every 5 days for 5 consecutive doses. The course was repeated at 3-week intervals. Most @entity1 received @entity1499 as outpatients. @entity1499 blood levels were measured 4 and 24 hours after administration in both groups. In the test group 10 of the 18 @entity1 showed complete @entity5 regression and were alive 21 to 50 months after the start of treatment. Partial regression was observed in 8 @entity1 . Hematological reserve remained unchanged. Mild @entity137 occurred in 3 @entity1 . Of the 8 @entity1 treated intravenously the @entity5 showed partial regression in 1, was stable in 3 and progressed in 4. Side effects were severe in 5 @entity1 . Our results show that @entity1499 injection is highly effective in the treatment of advanced @entity150 . It is safe, well tolerated and can be used on an outpatient basis.

title: Anal submucosal injection: a new route for drug administration in pelvic @entity5 . II. XXXX anal injection in the treatment of advanced @entity150 . Preliminary study.

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

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

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

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

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


abstract: The clinical efficacy of submucosal anal injections of @entity1499 in advanced @entity150 is investigated. An experimental study on 20 @entity19 has shown that @entity1499 injected into the anal submucosa has no clinicopathological effect on the anorectum. The clinical study comprised 18 @entity1 with advanced @entity150 (13 with stage T3 and 5 with stage T4 disease) as a test group in whom @entity1499 was injected into the anal submucosa and 8 (6 with stage T3 and 2 with stage T4 @entity5 ) treated concurrently with intravenous @entity1499 . The dose in both groups was 50 mg. every 5 days for 5 consecutive doses. The course was repeated at 3-week intervals. Most @entity1 received @entity1499 as outpatients. @entity1499 blood levels were measured 4 and 24 hours after administration in both groups. In the test group 10 of the 18 @entity1 showed complete @entity5 regression and were alive 21 to 50 months after the start of treatment. Partial regression was observed in 8 @entity1 . Hematological reserve remained unchanged. Mild @entity137 occurred in 3 @entity1 . Of the 8 @entity1 treated intravenously the @entity5 showed partial regression in 1, was stable in 3 and progressed in 4. Side effects were severe in 5 @entity1 . Our results show that @entity1499 injection is highly effective in the treatment of advanced @entity150 . It is safe, well tolerated and can be used on an outpatient basis.

title: Anal submucosal injection: a new route for drug administration in pelvic @entity5 . II. @entity1499 anal injection in the treatment of advanced XXXX . Preliminary study.

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


abstract: The clinical efficacy of submucosal anal injections of @entity1499 in advanced @entity150 is investigated. An experimental study on 20 @entity19 has shown that @entity1499 injected into the anal submucosa has no clinicopathological effect on the anorectum. The clinical study comprised 18 @entity1 with advanced @entity150 (13 with stage T3 and 5 with stage T4 disease) as a test group in whom @entity1499 was injected into the anal submucosa and 8 (6 with stage T3 and 2 with stage T4 @entity5 ) treated concurrently with intravenous @entity1499 . The dose in both groups was 50 mg. every 5 days for 5 consecutive doses. The course was repeated at 3-week intervals. Most @entity1 received @entity1499 as outpatients. @entity1499 blood levels were measured 4 and 24 hours after administration in both groups. In the test group 10 of the 18 @entity1 showed complete @entity5 regression and were alive 21 to 50 months after the start of treatment. Partial regression was observed in 8 @entity1 . Hematological reserve remained unchanged. Mild @entity137 occurred in 3 @entity1 . Of the 8 @entity1 treated intravenously the @entity5 showed partial regression in 1, was stable in 3 and progressed in 4. Side effects were severe in 5 @entity1 . Our results show that @entity1499 injection is highly effective in the treatment of advanced @entity150 . It is safe, well tolerated and can be used on an outpatient basis.

title: Anal submucosal injection: a new route for drug administration in pelvic XXXX . II. @entity1499 anal injection in the treatment of advanced @entity150 . Preliminary study.

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


abstract: @entity308 is common, often severe, and usually recurrent, and it carries an excess risk of mortality due to medical illness as well as suicide. At referral centers, recurrence risk averages 85% within 2-3 years of full recovery from an acute episode. The natural history of @entity308 is highly variable, but typically episodes las ca. 6 months, with cycles of ca. 2 years. Yet, most long-term treatment studies are limited to the year or two following recovery from an acute episode. Accordingly, available evidence best supports a relapse-preventing effect of tri-cyclic antidepressants or @entity1091 within the first months after apparent recovery but is less compelling regarding prevention of later recurrences of new episodes. Other treatments have not been evaluated systematically. The hypothesis that bipolarlike, but apparently unipolar, @entity1 might respond selectively to @entity1091 maintenance requires further testing. Knowledge of long-term dose-benefit and dose-risk relationships is starting to emerge for @entity1091 , but these relationships remain inadequately tested for antidepressants. Actual levels of clinical treatment of @entity308 appear to fall short of the ideal, and much additional research and education is required to improve care in this very common disorder.

title: Is there a long-term protective effect of mood-altering agents in unipolar XXXX ?

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

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


abstract: Lipoproteins suppress several immune functions (mitogen-induced lymphoblast transformation, macrophage functions). Low density lipoprotein (LDL) is responsible for most of these effects. Diet may cause an elevation in LDL level. Therefore, we investigated the effect of @entity165 -rich diet upon the mitogen response of @entity35 . The @entity165 and LDL- @entity165 level of @entity35 was elevated after 8 days of diet. The blastogenic response of spleen cells separated by Ficoll-Paque gradient decreased. The response to phytomitogens 1, and 10 micrograms/ml phytohaemagglutinin (PHA) and 10 micrograms/ml concanavalin A (Con A) was measured by @entity1014 incorporation after 3 days of culture. The decrease of blastogenic response was more pronounced at the higher doses (10 micrograms/ml PHA, and 10 micrograms/ml Con A). For the lymphocyte cultures that did not contain autologous (rat) serum, we suggest that suppressed response was caused by an alteration of either in the membrane or in the metabolism of cells participating in the mitogen response. The decreased amount of LDL receptors and a derangement in intracellular @entity165 biosynthesis are supposed. The clinical implications of the immunosuppressive effect of dietary @entity165 is discussed.

title: [Effect of hyperlipemia on mitogen-induced blastogenesis in lymphocytes isolated from the XXXX spleen].

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

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

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


abstract: Wound healing is a complex process of which growth and motility are essential features. The aim of this study was to search for keratinocyte-derived secreted factors that may play a role in these mechanisms, and their corresponding receptors. Growth and motility factors were purified from conditioned medium from cultured primary keratinocytes. Receptor and growth factor expression profiles were investigated by immunohistochemical, western blotting, and in situ hybridization analysis on cultured keratinocytes and tissue sections derived from chronic wounds. The most potent autocrine growth factor for keratinocytes, which it was possible to purify and sequence from keratinocyte-conditioned medium, is @entity1915 . Its receptor @entity470 is up-regulated on the membranes of keratinocytes lining the edge of the wound. From the same keratinocyte-conditioned medium, heregulin-alpha was purified as a potent motility factor for keratinocytes. Its receptor is @entity7514 , which is up-regulated on the membranes of keratinocytes lining the edge of the wound and on keratinocytes that had migrated towards the centre of the wound. @entity12251 - another receptor for heregulin-alpha - is weakly present in occasional cells near the edge of the wound. The co-receptor for @entity7514 and @entity12251 is @entity1722 , which is also present in epidermal cells but not overexpressed. This study shows that heregulin-alpha is a potent motility factor for normal epithelial cells and that it plays a central role in the process of wound healing of stratified epithelia. Heregulin-alpha has already been shown to be the motility factor leading to migration of @entity1722 / @entity1722 -overexpressing @entity0 cells. The role of @entity1915 as a growth factor and of heregulin-alpha as a motility factor for keratinocytes in epidermal and @entity33 healing parallels their motility and growth induction in @entity105 .

title: The role of heregulin-alpha as a motility factor and XXXX as a growth factor in wound healing.

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

entities_list: @entity33 :: ('MESH:D052016', 'Disease') :: ['mucosal wound']

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

answer: @entity1915 :: (374,Gene) :: ['amphiregulin']


abstract: Previously, we demonstrated that Ia+ epidermal cells (EC) have @entity778 ( @entity778 ) antigen-presenting capacity in vitro and play an important role in resistance to @entity2025 in vivo. In the present study, we investigated the effects of in vivo ultraviolet (UV) irradiation of the skin on the @entity778 -immunity function of EC both in vitro and in vivo and on the pathogenesis of @entity2025 . Immune T cells cultured with EC and @entity778 antigen showed a proliferative response in vitro. Exposure of the skin to UV light 1 to 3 days before preparation of EC resulted in dose-dependent impairment of this proliferation. This UV-induced impairment of the accessory cell function of EC was accompanied by a parallel reduction of the number of Ia+ EC. We also transferred these EC-stimulated T cells to intracutaneously infected @entity19 . Immune T cells stimulated with EC obtained from irradiated @entity19 did not effectively clear @entity778 and allowed development of zosteriform @entity272 . In contrast normal-EC-stimulated immune T cells completely prevented the formation of a zosteriform @entity1910 . In addition, @entity19 irradiated with UV on shaved midflank skin 2 days before intracutaneous inoculation of @entity778 showed increased severity of @entity281 and a higher incidence of latency compared with control @entity19 . These studies indicate that in vivo UV irradiation of the skin abrogates the immune function of EC both in vitro and in vivo, and affects @entity778 pathogenesis. The implication of our results for the better understanding of the effect of UV on acute and recurrent @entity2025 is discussed.

title: The effects of ultraviolet irradiation of the XXXX : alteration in immune function mediated by epidermal cells and in the course of @entity281 .

entities_list: @entity778 :: ('MESH:D015658', 'Disease') :: ['HSV', 'herpes simplex virus']

entities_list: @entity2025 :: ('MESH:D020031', 'Disease') :: ['HSV infections', 'HSV infection']

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

entities_list: @entity272 :: ('MESH:D012871', 'Disease') :: ['skin lesions']

answer: @entity2025 :: (MESH:D020031,Disease) :: ['skin on herpes simplex virus infection']


abstract: Previously, we demonstrated that Ia+ epidermal cells (EC) have @entity778 ( @entity778 ) antigen-presenting capacity in vitro and play an important role in resistance to @entity2025 in vivo. In the present study, we investigated the effects of in vivo ultraviolet (UV) irradiation of the skin on the @entity778 -immunity function of EC both in vitro and in vivo and on the pathogenesis of @entity2025 . Immune T cells cultured with EC and @entity778 antigen showed a proliferative response in vitro. Exposure of the skin to UV light 1 to 3 days before preparation of EC resulted in dose-dependent impairment of this proliferation. This UV-induced impairment of the accessory cell function of EC was accompanied by a parallel reduction of the number of Ia+ EC. We also transferred these EC-stimulated T cells to intracutaneously infected @entity19 . Immune T cells stimulated with EC obtained from irradiated @entity19 did not effectively clear @entity778 and allowed development of zosteriform @entity272 . In contrast normal-EC-stimulated immune T cells completely prevented the formation of a zosteriform @entity1910 . In addition, @entity19 irradiated with UV on shaved midflank skin 2 days before intracutaneous inoculation of @entity778 showed increased severity of @entity281 and a higher incidence of latency compared with control @entity19 . These studies indicate that in vivo UV irradiation of the skin abrogates the immune function of EC both in vitro and in vivo, and affects @entity778 pathogenesis. The implication of our results for the better understanding of the effect of UV on acute and recurrent @entity2025 is discussed.

title: The effects of ultraviolet irradiation of the @entity2025 : alteration in immune function mediated by epidermal cells and in the course of XXXX .

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


abstract: A phylogeny of haemosporidian parasites (phylum Apicomplexa, family Plasmodiidae) was recovered using mitochondrial @entity68216 gene sequences from 52 species in 4 genera ( @entity3964 , Hepatocystis, Haemoproteus, and Leucocytozoon), including parasite species infecting mammals, birds, and reptiles from over a wide geographic range. Leucocytozoon species emerged as an appropriate out-group for the other @entity4801 . Both parsimony and maximum-likelihood analyses produced similar phylogenetic trees. Life-history traits and parasite morphology, traditionally used as taxonomic characters, are largely phylogenetically uninformative. The @entity3964 and Hepatocystis species of @entity1 hosts form 1 well-supported clade, and the @entity3964 and Haemoproteus species of birds and lizards form a second. Within this second clade, the relationships between taxa are more complex. Although jackknife support is weak, the @entity3964 of birds may form 1 clade and the Haemoproteus of birds another clade, but the parasites of lizards fall into several clusters, suggesting a more ancient and complex evolutionary history. The parasites currently placed within the genus Haemoproteus may not be monophyletic. @entity3964 of @entity1 was not derived from an avian malarial ancestor and, except for its close sister species, @entity12255 , is only distantly related to haemospordian parasites of all other mammals. @entity3964 is paraphyletic with respect to 2 other genera of @entity4801 , Haemoproteus and Hepatocystis. Explicit hypothesis testing supported these conclusions.

title: A molecular phylogeny of @entity4801 recovered from XXXX gene sequences.

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

entities_list: @entity3964 :: ('5833', 'Species') :: ['Plasmodium falciparum', 'Plasmodium']

entities_list: @entity4801 :: ('MESH:D010272', 'Disease') :: ['malarial parasites']

answer: @entity68216 :: (2655541(Tax:5833),Gene) :: ['cytochrome b']


abstract: A phylogeny of haemosporidian parasites (phylum Apicomplexa, family Plasmodiidae) was recovered using mitochondrial @entity68216 gene sequences from 52 species in 4 genera ( @entity3964 , Hepatocystis, Haemoproteus, and Leucocytozoon), including parasite species infecting mammals, birds, and reptiles from over a wide geographic range. Leucocytozoon species emerged as an appropriate out-group for the other @entity4801 . Both parsimony and maximum-likelihood analyses produced similar phylogenetic trees. Life-history traits and parasite morphology, traditionally used as taxonomic characters, are largely phylogenetically uninformative. The @entity3964 and Hepatocystis species of @entity1 hosts form 1 well-supported clade, and the @entity3964 and Haemoproteus species of birds and lizards form a second. Within this second clade, the relationships between taxa are more complex. Although jackknife support is weak, the @entity3964 of birds may form 1 clade and the Haemoproteus of birds another clade, but the parasites of lizards fall into several clusters, suggesting a more ancient and complex evolutionary history. The parasites currently placed within the genus Haemoproteus may not be monophyletic. @entity3964 of @entity1 was not derived from an avian malarial ancestor and, except for its close sister species, @entity12255 , is only distantly related to haemospordian parasites of all other mammals. @entity3964 is paraphyletic with respect to 2 other genera of @entity4801 , Haemoproteus and Hepatocystis. Explicit hypothesis testing supported these conclusions.

title: A molecular phylogeny of XXXX recovered from @entity68216 gene sequences.

answer: @entity4801 :: (MESH:D010272,Disease) :: ['malarial parasites']


abstract: INTRODUCTION: Measurements of pulmonary vein (PV) flow with intracardiac echocardiography (ICE) immediately before and after PV isolation may be a useful method for predicting which @entity1 will develop @entity849 . METHODS AND RESULTS: We assessed preablation and postablation flows in each of the four PVs using a phase-array ICE catheter in 95 @entity1 (mean age 52 +/- 13) undergoing @entity955 ablation. The ostium of each of the PVs was defined using angiography, electrical mapping, and ICE imaging. Ostial electrical isolation of all PVs was achieved using a 4-mm cooled-tip radiofrequency ablation catheter. Change in PV flow, when present, was examined as both an absolute value and as a percentage of the baseline flow. All @entity1 underwent spiral computed tomography (CT) scans of the PVs 3 months after the procedure for detection of @entity850 . The average preablation diastolic flows for the left superior, left inferior, right superior, and right inferior veins were 0.56, 0.54, 0.47, and 0.45 m/sec, respectively. These values increased to 0.74, 0.67, 0.58, and 0.59 m/sec postablation (P < 0.001). Of 380 PVs ablated, the CT scans revealed 2 (1%) with severe (>70%) @entity850 , 13 (3%) with moderate (51%-70%) @entity850 , and 62 (16%) with mild (< or = 50%) @entity850 . The r value between flow and @entity850 was only 0.09 (P = NS). CONCLUSION: Acute changes in PV flow immediately after ostial PV isolation do not appear to be a strong predictor of @entity849 .

title: Use of intracardiac echocardiography for prediction of chronic XXXX after ablation of @entity955 .

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

entities_list: @entity849 :: ('MESH:D011666', 'Disease') :: ['chronic PV stenosis']

entities_list: @entity850 :: ('MESH:D003251', 'Disease') :: ['stenosis']

entities_list: @entity955 :: ('MESH:D001281', 'Disease') :: ['atrial fibrillation']

answer: @entity849 :: (MESH:D011666,Disease) :: ['pulmonary vein stenosis']


abstract: INTRODUCTION: Measurements of pulmonary vein (PV) flow with intracardiac echocardiography (ICE) immediately before and after PV isolation may be a useful method for predicting which @entity1 will develop @entity849 . METHODS AND RESULTS: We assessed preablation and postablation flows in each of the four PVs using a phase-array ICE catheter in 95 @entity1 (mean age 52 +/- 13) undergoing @entity955 ablation. The ostium of each of the PVs was defined using angiography, electrical mapping, and ICE imaging. Ostial electrical isolation of all PVs was achieved using a 4-mm cooled-tip radiofrequency ablation catheter. Change in PV flow, when present, was examined as both an absolute value and as a percentage of the baseline flow. All @entity1 underwent spiral computed tomography (CT) scans of the PVs 3 months after the procedure for detection of @entity850 . The average preablation diastolic flows for the left superior, left inferior, right superior, and right inferior veins were 0.56, 0.54, 0.47, and 0.45 m/sec, respectively. These values increased to 0.74, 0.67, 0.58, and 0.59 m/sec postablation (P < 0.001). Of 380 PVs ablated, the CT scans revealed 2 (1%) with severe (>70%) @entity850 , 13 (3%) with moderate (51%-70%) @entity850 , and 62 (16%) with mild (< or = 50%) @entity850 . The r value between flow and @entity850 was only 0.09 (P = NS). CONCLUSION: Acute changes in PV flow immediately after ostial PV isolation do not appear to be a strong predictor of @entity849 .

title: Use of intracardiac echocardiography for prediction of chronic @entity849 after ablation of XXXX .

answer: @entity955 :: (MESH:D001281,Disease) :: ['atrial fibrillation']


abstract: BACKGROUND: The authors present a new method for the reconstruction of large or complex-formed cranial bone defects using prefabricated, computer-generated, individual CFRP ( @entity505 fibre reinforced plastics) medical grade implants. METHOD: CFRP is a composite material containing @entity505 fibres embedded in an @entity990 resin matrix. It is radiolucent, heat-resistant, extremely strong and light (its weight is 20% that of @entity11555 ), has a modulus of elasticity close to that of bone, and an established biocompatibility. The utilisation of a CAD/CAM (computer aided design/computer aided manufacture) technique based on digitised computed tomography (CT) data, with stereolithographic modelling as intermediate step, enabled the production of individual, prefabricated CFRP medical grade implants with an arithmetical maximum aberration in extension of less than +/-0.25 mm. Between 1995 and February 2002, 29 @entity1 (15 @entity1 and 14 @entity1 ; mean age, 39.9 years; range, 16 to 67 years) underwent cranioplasty with CFRP medical grade implants at the neurosurgical department of the University of Vienna. Twenty-four @entity1 were repaired secondarily (delayed cranioplasty) while 5 were repaired immediately following craniectomy (single stage cranioplasty). All cases were assessed for the accuracy of the intra-operative fit of the implant, restoration of the natural skull contour and aesthetics and adverse symptoms. FINDINGS: The intra-operative fit was excellent in 93.1% and good in 6.9% of the implants. In two cases minor adjustments of the bony margin of the defect were required. The operating time for insertion ranged from 16 to 38 minutes, median 21 minutes. Postoperatively, 86.2% of the @entity1 graded the restoration of their natural skull shape and symmetry as excellent while 13.8% termed it good. In one @entity1 a non-space occupying @entity11757 was found at the follow-up, but required no intervention. Two @entity1 experienced @entity194 of the frontal portion of the temporal muscle while one @entity1 had a transient @entity2103 . Over the mean follow-up period of 3.3 years (range, 0.08 to 6.8 years), there were no adverse reactions and no plate had to be removed. INTERPRETATION: Individual, prefabricated CFRP medical grade implants may be considered as an alternative to conventionally utilised materials for cranioplasty, in particular in the challenging group of @entity1 with extensive @entity129 or more complex-formed defects of the fronto-orbital or temporo-zygomatic region, guaranteeing short operating times and excellent functional and aesthetic results, which justifies the expense of their production.

title: Cranioplasty with individual XXXX fibre reinforced polymere (CFRP) medical grade implants based on CAD/CAM technique.

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

entities_list: @entity129 :: ('MESH:D003389', 'Disease') :: ['cranial defects']

entities_list: @entity2103 :: ('MESH:D005155', 'Disease') :: ['palsy of the frontal branch of the facial nerve']

entities_list: @entity11757 :: ('MESH:D013353', 'Disease') :: ['subdural hygroma']

answer: @entity505 :: (MESH:D002244,Chemical) :: ['carbon']


abstract: Changes in glycolytic flux have been observed in liver under conditions where effects of @entity268 seem unlikely. We have, therefore, studied the phosphorylation of four enzymes involved in the regulation of glycolysis and gluconeogenesis (6-phosphofructo-1-kinase from @entity35 liver and @entity95 muscle; @entity2388 kinase, 6-phosphofructo-2-kinase and @entity948 -1,6-bisphosphatase from @entity35 liver) by defined concentrations of two @entity268 -independent protein kinases: @entity141 /calmodulin-dependent protein kinase and @entity141 /phospholipid-dependent protein kinase (protein kinase C). The results were compared with those obtained with the catalytic subunit of @entity268 -dependent protein kinase. The following results were obtained. 1. @entity141 /calmodulin-dependent protein kinase phosphorylates 6-phosphofructo-1-kinase and L-type @entity2388 kinase at a slightly lower rate as compared to @entity268 -dependent protein kinase. 2. 6-Phosphofructo-1-kinase is phosphorylated by the two kinases at a single identical position. There is no additive phosphorylation. The final stoichiometry is 2 mol @entity1391 /mol tetramer. The same holds for L-type @entity2388 kinase except that the stoichiometry with either kinase or both kinases together is 4 mol @entity1391 /mol tetramer. 3. @entity95 muscle 6-phosphofructo-1-kinase is phosphorylated by @entity268 -dependent protein kinase but not by @entity141 /calmodulin-dependent protein kinase. 4. Fructose-1,6-bisphosphatase from @entity35 but not from @entity95 liver is phosphorylated at the same position but at a markedly lower rate by @entity141 /calmodulin-dependent protein kinase when compared to the phosphorylation by @entity268 -dependent protein kinase. 5. 6-Phosphofructo-2-kinase is phosphorylated by @entity141 /calmodulin-dependent protein kinase only at a negligible rate. 6. Protein kinase C does not seem to be involved in the regulation of the enzymes examined: only 6-phosphofructo-2-kinase became phosphorylated to a significant degree. In contrast to the phosphorylation by @entity268 -dependent protein kinase, this phosphorylation is not associated with a change of enzyme activity. This agrees with our observation that the sites of phosphorylation by the two kinases are different. The results indicate that @entity141 /calmodulin-dependent protein kinase but not protein kinase C could be involved in the regulation of hepatic glycolytic flux under conditions where changes in the activity of @entity268 -dependent protein kinase seem unlikely.

title: Are calcium-dependent protein kinases involved in the regulation of glycolytic/gluconeogenetic enzymes? Studies with XXXX /calmodulin-dependent protein kinase and protein kinase C.

entities_list: @entity948 :: ('MESH:D005632', 'Chemical') :: ['fructose']

entities_list: @entity95 :: ('9986', 'Species') :: ['rabbit', 'Rabbit']

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

entities_list: @entity2388 :: ('MESH:D019289', 'Chemical') :: ['pyruvate']

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


abstract: We studied diurnal variation and the responses of plasma corticoids to @entity619 and ACTH before and after adrenal surgery in 11 @entity1 with @entity1368 . Diurnal variation of plasma corticoids was examined in all cases. Before adrenal surgery, plasma @entity1369 (Ald) was higher at all times, @entity8147 ( @entity4420 ) was high value at 5:00 and then normal value, @entity4419 (S) was high value at 5:00 and 9:00, thereafter normal value, while @entity2819 (B) and @entity701 (F) were almost normal value at all times. The circadian rhythm was observed in these corticoids. @entity619 (2 mg/day) was administered to 8 @entity1 for 10 days. Plasma Ald and @entity4420 were significantly suppressed only at 5:00, while B, S and F almost suppressed at all times. After dexa suppression, the circadian rhythm of Ald still observed, while the diurnal variation of the other corticoids was even. ACTH (1 microgram) was injected intravenously to 9 @entity1 . Responses of @entity4420 , B and Ald were higher, and of S and F were almost normal. Diurnal variation of plasma corticoids was observed after 1 month of adrenal surgery. Ald was lower, the other corticoids were normal values. ACTH (1 microgram) was injected to the same case before surgery. Responses of these corticoids to ACTH were slightly lower. Contents of Ald in @entity652 tissues were higher than those in adjacent and normal adrenal tissues, and the contents of the other corticoids in @entity652 tissue were almost normal value. As these results showed, before surgery these corticoids were secreted from @entity652 without ACTH, although these were responsible to ACTH, and the presence of regulative factor of circadian rhythm except ACTH was suggested. After surgery, not only the responses to ACTH of mineralocorticoids but these of glucocorticoids decreased.

title: [Diurnal variation and responses of corticoids to @entity619 and ACTH before and after adrenal surgery in XXXX ].

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

entities_list: @entity2819 :: ('MESH:D003345', 'Chemical') :: ['corticosterone']

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

entities_list: @entity8147 :: ('MESH:D003900', 'Chemical') :: ['deoxycorticosterone']

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

entities_list: @entity4419 :: ('MESH:D003350', 'Chemical') :: ['11-deoxycortisol']

entities_list: @entity1368 :: ('MESH:D006929', 'Disease') :: ['primary aldosteronism']

answer: @entity1368 :: (MESH:D006929,Disease) :: ['primary aldosteronism']


abstract: We studied diurnal variation and the responses of plasma corticoids to @entity619 and ACTH before and after adrenal surgery in 11 @entity1 with @entity1368 . Diurnal variation of plasma corticoids was examined in all cases. Before adrenal surgery, plasma @entity1369 (Ald) was higher at all times, @entity8147 ( @entity4420 ) was high value at 5:00 and then normal value, @entity4419 (S) was high value at 5:00 and 9:00, thereafter normal value, while @entity2819 (B) and @entity701 (F) were almost normal value at all times. The circadian rhythm was observed in these corticoids. @entity619 (2 mg/day) was administered to 8 @entity1 for 10 days. Plasma Ald and @entity4420 were significantly suppressed only at 5:00, while B, S and F almost suppressed at all times. After dexa suppression, the circadian rhythm of Ald still observed, while the diurnal variation of the other corticoids was even. ACTH (1 microgram) was injected intravenously to 9 @entity1 . Responses of @entity4420 , B and Ald were higher, and of S and F were almost normal. Diurnal variation of plasma corticoids was observed after 1 month of adrenal surgery. Ald was lower, the other corticoids were normal values. ACTH (1 microgram) was injected to the same case before surgery. Responses of these corticoids to ACTH were slightly lower. Contents of Ald in @entity652 tissues were higher than those in adjacent and normal adrenal tissues, and the contents of the other corticoids in @entity652 tissue were almost normal value. As these results showed, before surgery these corticoids were secreted from @entity652 without ACTH, although these were responsible to ACTH, and the presence of regulative factor of circadian rhythm except ACTH was suggested. After surgery, not only the responses to ACTH of mineralocorticoids but these of glucocorticoids decreased.

title: [Diurnal variation and responses of corticoids to XXXX and ACTH before and after adrenal surgery in @entity1368 ].

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

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


abstract: The effect of dietary manipulation of fat and fibre on the structural and cell kinetic characteristics of @entity694 was studied before and during experimental @entity105 in 232 male Albino Swiss @entity35 . Carcinogen treated animals were given 12 weekly injections of @entity2985 (10 mg/kg/week). The animals were divided between four dietary groups (1) high fat, high fibre, (2) low fat, high fibre, (3) high fat, low fibre and (4) low fat, low fibre. Pathological and cell kinetic information together with details of certain faecal characteristics was collected when the animals were killed 4, 20, and 28 weeks after starting their experimental diet. @entity5 induction was significantly influenced by diet. The highest risk of @entity14 development was found in groups fed diet 3: high fat, low fibre (p less than 0.03). In contrast, diet 2: low fat, high fibre was associated with the lowest risk. The proportion of histologically proven @entity5 occurring in each dietary group was: @entity71003 -10.9%, diet 2-3.6%, diet 3-63.7%, diet 4-21.8%. Scanning electron microscopic (SEM) studies done on selected samples indicated both dietary and @entity2985 related alterations in crypt unit integrity. The most marked surface architectural changes were seen in carcinogen treated animals maintained on diet 3 (high fat, low fibre). Stathmokinetic analysis revealed considerable intergroup variability. Both fat and fibre produced significant effects, principally during the preneoplastic phase of @entity105 . Faster proliferative activity tended to be found in animals at low risk of @entity5 induction (diet 2), slower proliferation being more characteristic of animals at high risk (p less than 0.05). The findings suggest that both topographical and cell kinetic parameters have an important relationship with promoting and protecting dietary factors during the development of @entity14 .

title: Morphological and cell kinetic effects of dietary manipulation during XXXX .

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

entities_list: @entity2985 :: ('MESH:D001397', 'Chemical') :: ['azoxymethane']

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

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

entities_list: @entity694 :: ('MESH:D003110', 'Disease') :: ['colonic mucosa']

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


abstract: The spatial arrangement of the F protein spike in the @entity7686 was studied after purifying the protein and reconstituting it in lipid vesicles (Sechoy, O., Philippot, J. R., and Bienvenue, A. (1986) Biochim. Biophys. Acta 857, 1-12). The different components of the F protein spikes were analyzed by @entity3208 - @entity2975 gel electrophoresis under various conditions of treatment, i.e. at different temperatures and @entity3208 concentrations, using different detergents for F protein solubilization (Triton X-100 and @entity6072 ), by fast protein liquid chromatography analysis, and by chemical cross-linking between subunits with bifunctional agents such as @entity63751 and @entity11750 . The F protein spike appeared to be a structurally stable complex, composed of a noncovalent association of four homooligomers, each consisting of two peptides, F1 and F2, linked by a @entity1520 bond. @entity6072 and @entity6000 solubilized the F protein, preserving the tetramer, which is probably the native form. Using chemical cross-linking, a covalent bond was formed between two monomers. We hypothesize that the tetrameric form of the F protein in its native form (spike) consists of two identical dimers that can be chemically cross-linked in a stable complex.

title: F protein-F protein interaction within the XXXX identified by native bonding or chemical cross-linking.

entities_list: @entity11750 :: ('MESH:C011240', 'Chemical') :: ['dithiobis(succinimidyl propionate)']

entities_list: @entity3208 :: ('MESH:D012967', 'Chemical') :: ['sodium dodecyl sulfate']

entities_list: @entity63751 :: ('MESH:D004119', 'Chemical') :: ['dimethyl adipimidate']

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

entities_list: @entity1520 :: ('CHEBI:48343', 'Chemical') :: ['disulfide']

entities_list: @entity6072 :: ('MESH:C018619', 'Chemical') :: ['octyl glucoside', 'Octyl glucoside']

answer: @entity7686 :: (11191,Species) :: ['Sendai virus']


abstract: Polyclonal antibodies against @entity141 /calmodulin-dependent protein kinase II (CaM kinase II) of @entity35 brain were prepared by immunizing @entity95 and then purified by antigen-affinity column. The antibodies which recognized both subunits of the enzyme with Mrs 49K and 60K were used for the study on the distribution of CaM kinase II in @entity406 -fixed, @entity982 -embedded tissues. In the brain, a light-microscopic study demonstrated strong immunoreactivity in neuronal somata and dendrites and weak immunoreactivity in nuclei. The densely stained regions included cerebral cortex, hippocampal formation, striatum, substantia nigra, and cerebellar cortex. In substantia nigra, neurites were stained, but not neuronal somata. Electron microscopy revealed that the immunoreactive product was highly concentrated at the postsynaptic densities. In addition to neurons, weak immunoreactivity was also demonstrated in glial cells, such as astrocytes and ependymal cells of ventricles and epithelial cells of choroid plexus. In other tissues, strong immunoreactivity was observed in the islet of pancreas and moderate immunoreactivity in skeletal muscle and kidney tubules. Immunoreactivity was demonstrated in all of the tissues tested. The results suggest that CaM kinase II is widely distributed in the tissues.

title: Immunohistochemical localization of XXXX /calmodulin-dependent protein kinase II in @entity35 brain and various tissues.

entities_list: @entity406 :: ('MESH:D005557', 'Chemical') :: ['formalin']

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

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


abstract: Polyclonal antibodies against @entity141 /calmodulin-dependent protein kinase II (CaM kinase II) of @entity35 brain were prepared by immunizing @entity95 and then purified by antigen-affinity column. The antibodies which recognized both subunits of the enzyme with Mrs 49K and 60K were used for the study on the distribution of CaM kinase II in @entity406 -fixed, @entity982 -embedded tissues. In the brain, a light-microscopic study demonstrated strong immunoreactivity in neuronal somata and dendrites and weak immunoreactivity in nuclei. The densely stained regions included cerebral cortex, hippocampal formation, striatum, substantia nigra, and cerebellar cortex. In substantia nigra, neurites were stained, but not neuronal somata. Electron microscopy revealed that the immunoreactive product was highly concentrated at the postsynaptic densities. In addition to neurons, weak immunoreactivity was also demonstrated in glial cells, such as astrocytes and ependymal cells of ventricles and epithelial cells of choroid plexus. In other tissues, strong immunoreactivity was observed in the islet of pancreas and moderate immunoreactivity in skeletal muscle and kidney tubules. Immunoreactivity was demonstrated in all of the tissues tested. The results suggest that CaM kinase II is widely distributed in the tissues.

title: Immunohistochemical localization of @entity141 /calmodulin-dependent protein kinase II in XXXX brain and various tissues.

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


abstract: In several parts of the @entity20422 ) genome, nested sets of overlapping RNAs with common 3' or 5' termini have been recognized. In the present report, the pattern of viral transcription and the arrangement of viral gene products in the region of 81.2 to 85.0 map units were investigated. In this segment of the AcNPV genome, at least nine size classes of viral RNA were identified which ranged in size from 1.3 kilobases (kb) to 4.6 kb and exhibited common 3' termini. The detailed restriction map and the @entity377 sequence of this part of the AcNPV genome were determined. Computer analyses revealed several open reading frames (ORFs) on the rightward-transcribed strand with potential TATA and CAAT signals preceding many of the potential ORFs and the 5' termini of some of the mapped RNAs. The leftward-transcribed strand was devoid of major ORFs. The presumptive polypeptides encoded by the larger ORFs ranged in size from 11.3 to 55.6 kilodaltons (kDa). The @entity535 sequence of the presumptive polypeptide encoded by @entity20039 , a 33.6-kDa molecule, exhibited an unusual, clustered 16-fold repeat of the dipeptide @entity369 - @entity563 in a protein that showed an overall preponderance of basic @entity1522 . The results of in vitro translation experiments with hybrid-selected RNAs homologous to internal subfragments of the 81.2- to 85.0-map-unit region yielded polypeptides of approximately 28, 34 to 36, and 48 to 50 kDa, which were close in size to the lengths of the major ORFs derived from the @entity377 sequence. The localizations of individual size classes of RNAs in the 81.2- to 85.0-map-unit region of the viral genome were determined precisely at the 3' and 5' termini by S1 protection analyses. Within a sequence of eight nucleotides, all RNAs had the same 3' terminus, which lay close to multiple polyadenylation signals. The initiation sites of the nine different RNA size classes were precisely mapped. As the cap sites of the smaller RNAs (less than 1.8 kb) were determined by S1 protection analyses, a multitude of RNA initiation sites became apparent. It was also shown that the different RNA size classes in the 81.2- to 85.0-map-unit region were detectable as early as 2 h and at least until 36 to 48 h after infection. In unselected cytoplasmic RNA, the size classes of viral RNAs specific for the EcoRI J fragment were detectable early as well as late after infection, although at early times the larger RNAs were detectable in smaller amounts.(ABSTRACT TRUNCATED AT 400 WORDS)

title: Overlapping sets of viral RNAs reflect the array of polypeptides in the EcoRI J and N fragments (map positions 81.2 to 85.0) of the XXXX genome.

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

entities_list: @entity20422 :: ('46015', 'Species') :: ['Autographa californica nuclear polyhedrosis virus (AcNPV']

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

entities_list: @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide']

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

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

answer: @entity20422 :: (46015,Species) :: ['Autographa californica nuclear polyhedrosis virus']


abstract: In adult @entity95 does ovulation was induced by @entity1 choriongonadotropin (hCG) 48 hours before experiments. At laparotomy the oviducts were cannulated from the ovarian and uterine ends. In vivo as well as in vitro the patency of the isthmus was studied with low viscous fluid perfusion of the ampulloisthmic region in antegrade direction. Intraluminally applied @entity1063 (NE) or @entity2647 ( @entity815 ) caused dual changes in transisthmic flow; administration of a low dose increased the flow, while high doses decreased the flow in vivo. In vitro, application of PhE only induced a dose-dependent reduction of flow. The PhE-induced reduction of flow was prevented by pretreatment with @entity5333 in vivo and in vitro, suggesting activation of an alpha-adrenoceptor mechanism. Intraluminal application of @entity4183 (T) caused a dose-dependent increase of flow, which was most prominent in vivo. Such an increase of flow was prevented by blockade of beta-adrenoceptors with @entity1169 or by selective blockade of beta 2-adrenoceptors with @entity3465 399 both in vivo and in vitro, indicating activation of a beta 2-adrenoceptor mechanism. The biochemical and hormonal changes 48 hours after ovulation imply a role for the sympathetic transmitter NE in causing a contractile state of the ampulloisthmic region ("tube locking") for retention of ova prior to nidation in the uterine cavity. The isthmus would then hypothetically act as a sympathetically innervated smooth muscle sphincter. The present results demonstrate a constrictory response of this region to high-dose stimulation of alpha-adrenoceptors in support of such a hypothesis. However, it must be noted that this region also possesses a population of beta-adrenoceptors at this time interval, which may interfere with a constrictor mechanism via circulating epinephrine.

title: Adrenoceptor modulated flow through the XXXX ampulloisthmic region studied in vivo and in vitro.

entities_list: @entity1169 :: ('MESH:D011433', 'Chemical') :: ['propranolol']

entities_list: @entity5333 :: ('MESH:D010643', 'Chemical') :: ['phenoxybenzamine']

entities_list: @entity2647 :: ('MESH:D010656', 'Chemical') :: ['phenylephrine']

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

entities_list: @entity4183 :: ('MESH:D013726', 'Chemical') :: ['terbutaline']

answer: @entity95 :: (9986,Species) :: ['rabbit']


abstract: @entity8 ( @entity8 )-induced @entity1372 retention is normally mediated by alpha 1-adrenoceptors. Clinically, chronic @entity3159 therapy increases rather than decreases @entity1372 retention. In preliminary studies, chronic @entity3159 (3 days, 3 mg/kg per day) increased renal alpha 2-adrenoceptor density (mean +/- s.e.m., 153 +/- 14 versus 209 +/- 11 fmol/mg protein) in normal @entity35 . We therefore postulated that following chronic @entity3159 treatment, alpha 2-adrenoceptors may mediate @entity8 -induced @entity1372 retention. The effect of chronic @entity3159 pretreatment on the alpha-adrenoceptor subtype mediating @entity8 -induced antinatriuresis was studied in the perfused @entity35 kidney. In control @entity35 , subpressor levels of @entity8 (approximately 1 Hz, 10 V, 1 ms) decreased @entity1372 and water excretion. @entity3159 28 nmol/l (alpha 1-blockade) reversed this effect of @entity8 . @entity3160 300 nmol/l (alpha 2-blockade) had no effect. In @entity35 treated with @entity3159 , @entity8 again decreased @entity1372 and water excretion. In these @entity35 , @entity3160 as well as @entity3159 was necessary to reverse the effects of @entity8 . Thus, following @entity3159 pretreatment postjunctional alpha 2- as well as alpha 1-adrenoceptors mediated @entity8 -induced antinatriuresis. A similar function of the elevated renal alpha 2-adrenoceptors in @entity101 in @entity35 could possibly explain the mechanism by which excess @entity1372 retention occurs and thereby the elevation of blood pressure.

title: Alpha 1-adrenoceptor blockade and altered renal alpha 2-adrenoceptors: a model(?) for the study of genetically altered alpha 2-adrenoceptors in XXXX @entity35 .

entities_list: @entity3160 :: ('MESH:D015016', 'Chemical') :: ['yohimbine', 'Yohimbine']

entities_list: @entity8 :: ('MESH:D007674', 'Disease') :: ['RNS', 'Renal nerve stimulation']

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

entities_list: @entity3159 :: ('MESH:D011224', 'Chemical') :: ['Prazosin', 'prazosin']

answer: @entity101 :: (MESH:D006973,Disease) :: ['hypertensive']


abstract: @entity8 ( @entity8 )-induced @entity1372 retention is normally mediated by alpha 1-adrenoceptors. Clinically, chronic @entity3159 therapy increases rather than decreases @entity1372 retention. In preliminary studies, chronic @entity3159 (3 days, 3 mg/kg per day) increased renal alpha 2-adrenoceptor density (mean +/- s.e.m., 153 +/- 14 versus 209 +/- 11 fmol/mg protein) in normal @entity35 . We therefore postulated that following chronic @entity3159 treatment, alpha 2-adrenoceptors may mediate @entity8 -induced @entity1372 retention. The effect of chronic @entity3159 pretreatment on the alpha-adrenoceptor subtype mediating @entity8 -induced antinatriuresis was studied in the perfused @entity35 kidney. In control @entity35 , subpressor levels of @entity8 (approximately 1 Hz, 10 V, 1 ms) decreased @entity1372 and water excretion. @entity3159 28 nmol/l (alpha 1-blockade) reversed this effect of @entity8 . @entity3160 300 nmol/l (alpha 2-blockade) had no effect. In @entity35 treated with @entity3159 , @entity8 again decreased @entity1372 and water excretion. In these @entity35 , @entity3160 as well as @entity3159 was necessary to reverse the effects of @entity8 . Thus, following @entity3159 pretreatment postjunctional alpha 2- as well as alpha 1-adrenoceptors mediated @entity8 -induced antinatriuresis. A similar function of the elevated renal alpha 2-adrenoceptors in @entity101 in @entity35 could possibly explain the mechanism by which excess @entity1372 retention occurs and thereby the elevation of blood pressure.

title: Alpha 1-adrenoceptor blockade and altered renal alpha 2-adrenoceptors: a model(?) for the study of genetically altered alpha 2-adrenoceptors in @entity101 XXXX .

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


abstract: Teprotide, a nonapeptide isolated from the venom of a Brazilian pit viper, Bothrops jararaca, was the first @entity1289 ( @entity1289 ) inhibitor to be discovered and tested. It was found to be an effective, non-toxic antihypertensive agent as well as an afterload-reducing agent for @entity1 with @entity712 ( @entity712 ). The primary activity of @entity7710 resulted from blockade of the angiotensin I converting enzyme--the pivotal step in the renin-angiotensin- @entity1369 system (RAAS), and consequent reductions in @entity2178 levels. There was limited clinical testing for teprotide because of: its scarcity; the need for parenteral administration; and the subsequent discovery and synthesis of @entity3371 , the first orally active @entity1289 inhibitor. @entity3371 is the prototype oral @entity1289 inhibitor and has been extensively studied since the initiation of formal studies in 1976. Perhaps one of the most closely researched drugs in modern times, the experience with @entity3371 now includes more than 12,000 @entity1 studied in formalized trials and over 4,000,000 @entity1 treated world-wide by physicians for @entity101 and @entity712 . Enalapril ( @entity4688 ) is the first of what appears to be a growing number of analogues which are structurally and pharmacodynamically different from @entity3371 ; yet, they possess the same capacity for inhibiting the activity of @entity1289 . The side effect profile of @entity4688 (and presumably future) @entity1289 inhibitors appears to be similar to @entity3371 , though clearly more experience is needed with newer agents. The initial use of @entity3371 was troubled by a relatively high incidence of side effects which will form the focus of this discussion. Partially the result of incomplete pharmacokinetic information, @entity3371 was administered in early studies at dosages now recognised to be far in excess of those necessary for drug action. In addition, dosages were given without regard for @entity177 , now known to be the main excretory route of @entity3371 . The population of those @entity1 studied frequently had chronic, treatment-resistant @entity101 , often associated with concomitant end-organ disease (especially @entity8 ); and many additional factors further complicating the clinical setting, e.g. a relatively high incidence of @entity1413 and immunosuppressive treatments.(ABSTRACT TRUNCATED AT 400 WORDS)

title: Adverse reactions with @entity1289 ( XXXX ) inhibitors.

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

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

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

entities_list: @entity1289 :: ('1636', 'Gene') :: ['angiotensin converting enzyme', 'ACE']

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

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

entities_list: @entity2178 :: ('183', 'Gene') :: ['angiotensin II']

entities_list: @entity7710 :: ('MESH:D013722', 'Chemical') :: ['teprotide']

entities_list: @entity3371 :: ('CHEBI:3380', 'Chemical') :: ['Captopril', 'captopril']

entities_list: @entity177 :: ('MESH:D051437', 'Disease') :: ['deficiencies of renal function']

entities_list: @entity1413 :: ('MESH:D003095', 'Disease') :: ['collagen vascular disease']

answer: @entity1289 :: (1636,Gene) :: ['ACE']


abstract: Teprotide, a nonapeptide isolated from the venom of a Brazilian pit viper, Bothrops jararaca, was the first @entity1289 ( @entity1289 ) inhibitor to be discovered and tested. It was found to be an effective, non-toxic antihypertensive agent as well as an afterload-reducing agent for @entity1 with @entity712 ( @entity712 ). The primary activity of @entity7710 resulted from blockade of the angiotensin I converting enzyme--the pivotal step in the renin-angiotensin- @entity1369 system (RAAS), and consequent reductions in @entity2178 levels. There was limited clinical testing for teprotide because of: its scarcity; the need for parenteral administration; and the subsequent discovery and synthesis of @entity3371 , the first orally active @entity1289 inhibitor. @entity3371 is the prototype oral @entity1289 inhibitor and has been extensively studied since the initiation of formal studies in 1976. Perhaps one of the most closely researched drugs in modern times, the experience with @entity3371 now includes more than 12,000 @entity1 studied in formalized trials and over 4,000,000 @entity1 treated world-wide by physicians for @entity101 and @entity712 . Enalapril ( @entity4688 ) is the first of what appears to be a growing number of analogues which are structurally and pharmacodynamically different from @entity3371 ; yet, they possess the same capacity for inhibiting the activity of @entity1289 . The side effect profile of @entity4688 (and presumably future) @entity1289 inhibitors appears to be similar to @entity3371 , though clearly more experience is needed with newer agents. The initial use of @entity3371 was troubled by a relatively high incidence of side effects which will form the focus of this discussion. Partially the result of incomplete pharmacokinetic information, @entity3371 was administered in early studies at dosages now recognised to be far in excess of those necessary for drug action. In addition, dosages were given without regard for @entity177 , now known to be the main excretory route of @entity3371 . The population of those @entity1 studied frequently had chronic, treatment-resistant @entity101 , often associated with concomitant end-organ disease (especially @entity8 ); and many additional factors further complicating the clinical setting, e.g. a relatively high incidence of @entity1413 and immunosuppressive treatments.(ABSTRACT TRUNCATED AT 400 WORDS)

title: Adverse reactions with XXXX ( @entity1289 ) inhibitors.

answer: @entity1289 :: (1636,Gene) :: ['angiotensin converting enzyme']