Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiviral activity and cytotoxicity of (E)-5-(2-bromovinyl)-2'-deoxycytidine (BrVdCyd) against herpes simplex virus type 1 (HSV-1), singly and in combination with deaminase inhibitors was determined using rabbit kidney (RK-13), HEP-2, BHK-21 and VERO cells. BrVdCyd was a potent inhibitor of HSV-1 replication with ED50 values of 0.30 to 1.20 microM depending on the cell line used. In the presence of tetrahydrouridine or tetrahydrodeoxyuridine (H4dUrd), potency of BrVdCyd increased approximately two fold (ED50: 0.54 microM) in HSV-infected VERO cells. The combination of BrVdCyd and H4dUrd was also effective in decreasing virus yield. Dihydrodeoxyuridine (H2dUrd) reversed the activity of BrVdCyd (ED50: 6 to 7 microM). The effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BrVdUrd), BrVdCyd and BrVdCyd in combination with H4dUrd on deoxyribonucleoside triphosphate (dNTP) pools was assessed in VERO cells infected with a high multiplicity of infection (10 PFU/cell). Significant differences in dNTP poll sizes (pmol/10(6) cell) were observed with different treatments. BrVdUrd and BrVdCyd treatment resulted in marked expansion of the dTTP pool (greater than 1200 pmol) compared to HSV-infected VERO cells (303 pmol). Exposure to H4dUrd resulted in a 12-fold expansion of the dCTP pool (326 pmol) and barely detectable levels of dTTP (less than 1.0 pmol). BrVdCyd plus H4dUrd treatment resulted in a slight expansion of the dTTP pool (515 pmol). These results indicate: (i) H4dUrd inhibits de novo dCyd/dCMP deaminase pathway and (ii) exposure to BrVdCyd plus H4dUrd puts a strain on viral DNA synthesis to such an extent that even though dTTP is being formed from alternative pathways, its eventual utilization as a substrate is reduced and hence it builds up.
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PMID:Antiherpes virus activity and effect on deoxyribonucleoside triphosphate pools of (E)-5-(2-bromovinyl)-2'-deoxycytidine in combination with deaminase inhibitors. 216 47

Continuous anticoagulation is required during haemofiltration to prevent the deposition of fibrin and the formation of thrombus which would lead to early clotting of the haemofilter. This study aimed to compare the efficiencies of 3 different anticoagulation protocol: 150 IU.kg-1.day-1 heparin (group HEP), 1.2 mg.kg-1.day-1 enoxaparin (group ENX), and a combination of 0.8 mg.kg-1.day-1 enoxaparin with 5 ng.kg-1.min-1 prostaglandin I2 (group ENX and PGI2). A flat ANS69S (Hospal) haemofilter was used for continuous venovenous haemofiltration. Antithrombotic efficiency was assessed with a haemofilter permeability index (HPI) including the transmembraneous pressure gradient and the rate of production of ultrafiltrate. The time required for HPI to decrease to 1/3 of its initial value (HPI1/3) was used to compare the 3 protocols. Treatment tolerance was judged by monitoring the usual haemodynamic and haemostatic parameters. No adverse effects (bleeding, thrombosis, hypotension) were observed. HPI1/3 was 15.1 +/- 2.4 h, 18.3 +/- 3.1 h and 28.2 +/- 4.2 h in groups HEP, ENX and ENX and PGI2 respectively. High dose enoxaparin reached antithrombotic efficiency without increasing the risk of haemorrhage. The use of low doses of prostaglandin I2 greatly increased HPI1/3, without any deleterious haemodynamic effects. However, the high cost of prostaglandin I2 needs to be put in the balance with the increase in duration of haemofilter life. Therefore, further investigations are required to evaluate the possible synergy between heparin and prostaglandin I2, as well as the biological parameters which need to be monitored.
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PMID:[Comparison of the antithrombotic effects of heparin, enoxaparin and prostacycline in continuous hemofiltration]. 216 13

The associated factors in 80 children (less than 2 yrs) with protracted diarrhea (greater than 21 days duration) and weight loss were: secondary carbohydrate intolerance (36): enteric pathogens (non typhoidal salmonella (11), enteropathogenic E. coli 'EPEC' (6), giardia (4), and shigella (3); cow's milk protein intolerance (3), gluten intolerance (3); miscellaneous (5); and undiagnosed enteropathy (9). Three of the EPEC showed localised pattern of adherence in vitro with HEP-2 cells. Most patients with salmonella and EPEC had severe secretory diarrhea with large fecal sodium losses. All 6 patients who died had secretory diarrhea and very high fecal sodium. All but 4 patients could be effectively managed with a chicken puree-glucose-coconut oil based diet.
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PMID:Associated factors of protracted diarrhea. 225 91

We have investigated the effect of six compactin-related compounds--mevinolin, compactin, ML-236A, monacolin X, monacolin L and dihydromonacolin L--on cholesterol synthesis in human umbilical vein endothelial cells, human small intestine epithelial cells, human hepatoma cell line HEP G2, normal human skin fibroblasts and in skin fibroblasts from a patient with familial homozygous hypercholesterolemia. The inhibition of cholesterol synthesis was found to depend on both the cell type and the type of compound used. The most effective compounds were mevinolin and compactin. Monacolin X, monacolin L and ML-236A were less effective, and dihydromonacolin L was the least efficacious. Endothelial and epithelial cells were sensitive to very low concentrations of inhibitors (IC50 = 1.0-30 pg/mL), HEP G2 cells required higher concentrations (IC50 = 0.01-66 ng/mL) and fibroblasts needed even higher concentrations (IC50 = 0.1-200 ng/mL). Lactone and acid forms of the inhibitors were equally active. None of the inhibitors had any effect on either protein or fatty acid synthesis in any of the cell types studied. It can be concluded that different compactin-related compounds show a range of potencies as cholesterol synthesis inhibitors and a dose-dependent tissue-selectivity.
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PMID:Comparison of the effect of six compactin-related compounds on cholesterol synthesis in five human cell types. 228 Jun 72

A four-applicator phased-array hyperthermia system with movable apertures (MA) is compared with an eight-applicator annular phased-array hyperthermia system with fixed apertures (AA) in terms of the HEP (hyperthermia equipment performance) values, based on two-dimensional models and the bioheat transfer equation. A hybrid element method is used to calculate the zeta-directed two-dimensional electric field with the inhomogeneities in tissue properties taken into account. The amplitudes and phases of each applicator are then optimized with the objective of uniform power deposition in the tumour and no power deposited in normal tissues. The temperature distributions under different blood flow conditions are obtained by solving the bioheat transfer equation using the finite element method. It is found that among the seven patient models studied, the MA and AA in general perform equally well when the tumour has zero blood flow, or equally poorly when the tumour has a blood flow larger than 5 ml/100 g per min. The performance of AA is often significantly better than that of MA when the tumour blood flow is 2.7 ml/100 g per min. The effects of different weighting functions are evaluated. We show that even if uniform absorbed power density (ARD = absorption rate density) could be achieved in the tumour volume with zero ARD in normal tissue the entire tumour would still not be brought to 43 degrees C or greater. However, it is found that the performance of uniform ARD in the tumour is on average far better than either the AA or MA, and choosing the uniform ARD as the objective function improved 35% of the cases for AA and 16% for MA. The optimization formula includes a weighting function that can be varied for different tissues. By decreasing the weights in regions of high blood flow the HEP values can sometimes be improved quite noticeably. Finally, the importance of the locations of applicators is studied. The results obtained indicate that the applicators should be placed about 5 cm or more away from the patient body (assuming water is the coupling medium) to ensure good HEP ratings.
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PMID:Theoretical investigation of a phased-array hyperthermia system with movable apertures. 229 35

Serum-free medium conditioned by the human hepatoma cell line HEP G2 was shown to contain a somatomedin-binding protein with a relative molecular mass of about 35,000. This binding protein was purified to homogeneity by the use of immunoaffinity chromatography and subsequent size exclusion chromatography. Antibodies for the immunoaffinity step were raised in rabbits against a previously isolated human amniotic fluid somatomedin-binding protein. The total composition and N-terminal amino acid sequence showed the protein to be identical to the binding protein from human amniotic fluid. Both have the N-terminal structure Ala-Pro-Trp-Gln-. The HEP G2 cell line offers a useful model to study the regulation of the synthesis and secretion of human somatomedin-binding proteins.
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PMID:The somatomedin-binding protein isolated from a human hepatoma cell line is identical to the human amniotic fluid somatomedin-binding protein. 240 14

Synthesis of virus-specific RNAs in human HEP-2 and L-41 cells chronically infected with measles virus was studied in comparison with synthesis of viral RNA in acutely infected L-41 cells. The RNA, a component of RNP isolated from chronically infected cells, was shown to be represented mainly by "minus" chains and to contain 23-25% "plus"-RNA. It was demonstrated by blotting hybridization that 1 species of genomic RNA with a molecular weight of 5 megadaltons was synthesized in acute infection whereas in chronically infected cells a small amount of subgenomic RNAs was additionally detected in RNP. The level of virus genome transcription in chronically infected cells was 7-8 fold lower than that in acute infection. The RNA-transcriptase activity of RNP isolated from chronically infected HEP-2 and L-41 cells was also lower than RNP activity from acutely infected L-41 cells. The observed features of virus-specific RNA synthesis in chronically infected cells seem to be likely to play a role in the maintenance of virus persistence.
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PMID:[RNA analysis of the measles virus in a human cell culture of the chronic infection]. 242 50

Monoclonal antibodies with fine specificities distinguishing alpha-fetoproteins of hepatoma (HEP-AFP) and yolk sac tumor (YST-AFP) origin have been obtained. These murine antibodies were produced by hybridomas made by fusion of X63-Ag8.653 myeloma cells with BALB/c spleen cells immunized with either HEP-AFP or YST-AFP and selected for their differential association with these antigens on the basis of Scatchard plot analysis. Three monoclonals (MA120, MA132 and MA136) selectively reacted with HEP-AFP. Their reactivity with YST-AFP was low. One monoclonal (MA122) reacted strongly with YST-AFP, whereas the reaction with HEP-AFP was significantly less strong. The difference in the association constants of these antibodies for the two AFPs appeared to be due to their specificity for the carbohydrate portions of the AFPs, which are different, at least in part. Indirect immunoperoxidase staining confirmed that MA122 was able to stain sections of an infantile embryonal carcinoma, but not of hepatoma.
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PMID:Monoclonal antibodies with fine specificities distinguishing alpha-fetoproteins of hepatoma and yolk sac tumor origin. 243 Sep 23

Three major functional characteristics of the insulin receptor are negative cooperativity, down-regulation, and beta-subunit tyrosine kinase activity. To investigate the inter-relationships among these functions we studied four antibodies to the insulin receptor alpha-subunit. These monoclonal antibodies competitively inhibited 125I-insulin binding to the insulin receptor of human IM-9 and HEP-G2 cells. When the antibodies were radiolabeled, insulin competed strongly with two antibodies (MA-10 and MA-51) for binding to the insulin receptor, but competed weakly with the two others (MA-5 and MA-20). Antibodies MA-10 and MA-51, like insulin, accelerated the dissociation of bound 125I-insulin from receptors; in contrast, MA-5 and MA-20 strongly inhibited 125I-insulin dissociation. Antibodies MA-10 and MA-51 induced down-regulation of insulin receptors with a potency similar to that of insulin. In contrast, MA-5 and MA-20 were more potent than insulin. None of the antibodies either alone or in combination influenced autophosphorylation of the insulin receptor beta-subunit. These data indicate, therefore, that two major epitopes can be identified on the alpha-subunit of the insulin receptor by the use of monoclonal antibodies. One epitope, recognized by antibodies MA-10 and MA-51, is close to or near the insulin-binding site and mimics insulin-induced negative cooperatively and down-regulation. The other epitope, recognized by antibodies MA-5 and MA-20, is at some distance from the insulin-binding site, and only mimics down-regulation. These data suggest, therefore, that: negative cooperativity and down-regulation may not be inter-related and both processes are independent of insulin receptor tyrosine kinase activity.
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PMID:Effect of monoclonal antibodies on human insulin receptor autophosphorylation, negative cooperativity, and down-regulation. 243 31

New blood vessel growth occurs during normal fetal development and in diseases such as cancer and diabetes. The polypeptide angiogenin induces new blood vessel growth in two biological assays and may play a role in the vascular development of the fetus and in the neovascularization that accompanies diseases and wound healing. A complementary DNA probe for human angiogenin was used to examine the tissue distribution of angiogenin messenger RNA (mRNA) in the developing rat and in selected transformed cell lines. Angiogenin mRNA was detected predominantly in adult liver but was also detectable at low levels in other tissues. The expression of the angiogenin gene in rat liver was found to be developmentally regulated; mRNA levels were low in the developing fetus, increased in the neonate, and maximal in the adult. The amount of angiogenin mRNA in human HT-29 colon carcinoma and SK-HEP hepatoma cells was not greater than that in normal rat liver. These results demonstrate that angiogenin is predominantly expressed in adult liver, that the pattern of angiogenin gene expression is not temporally related to vascular development in the rat, and that the transformed cells studied do not contain more angiogenin mRNA than does normal liver. If angiogenin activity is controlled at the transcriptional level, the results of this study suggest that the primary function of angiogenin in vivo may be in processes other than the regulation of vascular growth.
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PMID:Tissue distribution and developmental expression of the messenger RNA encoding angiogenin. 244 Jan 5


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