Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In four abnormal fibrinogens with a point mutation in the gamma chain, all characterized by impaired fibrin polymerization, we identified single base exchanges in the respective mutant gamma chain genes by polymerase chain reaction followed by DNA sequence analysis. These base exchanges accounted for the amino acid substitutions previously reported from our laboratory. They were exchanges of C to T (CGC for gamma Arg-275 to TGC for Cys) in fibrinogen Osaka II, T to G (AAT for gamma Asn-308 to AAG for Lys) in fibrinogen Kyoto I, T to C (ATG for gamma Met-310 to ACG for Thr) in fibrinogen Asahi, and G to T (GAT for gamma Asp-330 to TAT for Tyr) in fibrinogen Kyoto III. These base exchanges were found to reside in exon VIII of the gamma chain gene. Since many abnormal molecules are associated with polymerization defects, unless associated with the impaired release of fibrinopeptides A and/or B, exon VIII of the gamma chain gene may deserve careful study to define the structural alterations.
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PMID:Gene analyses of abnormal fibrinogens with a mutation in the gamma chain. 142 Nov 74

In a crossover study conducted with eight uremic patients maintained on hemodialysis, the Authors compared the effects of heparin (100 IU/kg at the start of dialysis) and defibrotide (400 mg at the start, repeated at 2 hours of ongoing dialysis) on the parameters of blood coagulation (VIII:C, AT III, TAT, PC antigen and activity, PS, and FPA), each being assessed before dialysis and at 2, 3 and 4 hours of the ongoing procedure. Heparin-assisted dialysis resulted in a significant rise of VIII:C and AT III; with defibrotide, instead, there was evidence of thrombin activation (increased FPA and TAT). PC levels were raised with both dialysis modalities; however, PC activity and PS levels were increased only in defibrotide-assisted dialysis. There were no adverse reactions or evidence of fibrin formation. These results confirm the antithrombotic activity of defibrotide in the course of dialysis and indicate that this action is independent of thrombin neutralization.
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PMID:Hemodialysis with defibrotide: effects on coagulation parameters. 142 6

The antitumor activity of a newly synthesized triphenylethylene derivative [(E)-4-[1-[4-[2-(dimethylamino)ethoxy-phenyl]-2-(4-isopropyl)phenyl-1- butenyl] phenyl monophosphate] (TAT-59) was investigated against human breast carcinoma xenografts in nude mice with reference to the changes of hormone receptors. Five strains (MCF-7, Br-10, R-27, ZR-75-1, and T-61) used for the experiments possessed cytosol estrogen receptor (ER), and their growth was estradiol dependent. Five mg of TAT-59 and tamoxifen citrate (TAM) per kg were administered p.o. daily except Sunday. TAT-59 showed a positive antitumor effect against MCF-7 and R-27, whereas TAM was effective on MCF-7, and their adverse effects detected by mortality rate, body weight loss, and spleen weight loss were similar to each other. The reduction of ER and production of progesterone receptor (PgR) after the treatment with TAT-59 were more potent than after TAM, suggesting that TAT-59 exerts its antitumor effect through binding to ER. These findings suggest that TAT-59 might merit use in clinical trials with breast cancers.
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PMID:Antitumor effect of triphenylethylene derivative (TAT-59) against human breast carcinoma xenografts in nude mice. 143 57

A certain nucleotide sequence in the promoter region of Vicia faba rRNA genes that specifically binds to a nuclear protein fraction has been identified by using a gel retardation assay and DNase I footprinting technique. The binding site of this protein fraction is located about 60 bp upstream from the initiation site of the pre-rRNA transcript. This location does not correspond with previously reported results on maize rRNA genes. However, both of the binding sites share a bi-partite consensus sequence, TAT-G(N)xCAGG. Methylation interference experiments show that two G residues in TATG and the complementary strand of CAGG are important for specific DNA-protein interaction. Furthermore, competition analyses using point-mutated synthetic DNAs show that two G residues in CAGG are essential for this interaction. Similar sequences are found in promoter regions of other plant and animal rRNA genes. We suggest that these sequences may be a cis-control element commonly involved in rRNA transcription.
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PMID:Characterization of nucleotide sequences that interact with a nuclear protein fraction in rRNA gene of Vicia faba. 146 30

In order to elucidate the activation of the coagulation cascade in patients with malignant neoplasms, we measured the levels of plasma prothrombin fragment F1 + 2, which is liberated in the process of thrombin generation. Twenty healthy adults (Group A), 29 patients with malignancies not complicated with DIC (Group B) and 4 patients with DIC (Group C) were evaluated. The values of F1 + 2 in Group C (2.38 +/- 0.55 nmol/l) were significantly higher (p < 0.01) than those in Group A (0.52 +/- 0.19 nmol/l) and B (0.86 +/- 0.68 nmol/l). Many patients in Group B showed higher levels of F1 + 2 compared to normal subjects, however, no significant differences were found between Group A and B. With respect to other coagulation molecular markers such as TAT, D-Dimer and PIC, F1 + 2 levels revealed positive correlation to those levels. Concerning the clinical course of DIC, elevated levels of F1 + 2 normalized much rapidly than those of TAT and D-Dimer by continuous administration of heparin. In conclusion, the measurement of plasma F1 + 2 is important in monitoring the activation of coagulation system in patients with malignancies, especially with respect to early detection and treatment of DIC.
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PMID:[Evaluation of hypercoagulable state in patients with malignancies by using prothrombin fragment F1 + 2]. 146 81

Molecular mechanics has been used to predict the structure of the Y+.R-.R(+)-type DNA triple helix, in which a second polypurine strand binds antiparallel to the homopurine strand of a homopurine/homopyrimidine stretch of duplex DNA. From calculations on the sequence d(C)10.d(G)10.d(G)10, two likely structures emerge. One has the glycosidic torsions of the third strand bases in the anti-conformation and Hoogsteen hydrogen-bonds to the purine strand of the duplex, the other has the third strand purines in the syn orientation and uses a reverse-Hoogsteen hydrogen-bonding pattern. Despite the large structural differences between these two types of triplex, calculations performed in vacuo with a distance-dependent dielectric constant to mimic the shielding effect of solvent show them to be energetically very similar, with the latter (syn) slightly preferred. However, if explicit solvent molecules are included in the calculation, the anti conformation is found to be much preferred. This difference in the results seems to stem from an underestimation of short-range electrostatic interactions in the in vacuo simulations. When TAA or TAT base triples are substituted for the sixth CGG triple in the sequence, it is found that, for the solvated model, the third strand base of the TAA triple prefers the syn orientation while that in the TAT triple retains a preference, though reduced, for the anti conformation.
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PMID:Prediction of the structure of the Y+.R-.R(+)-type DNA triple helix by molecular modelling. 148 Apr 74

Women at high risk for thromboembolism deserve prophylactic treatment with heparin in the course of pregnancy. Since activation of the coagulation system is associated with an increase of TAT complexes which may well precede the clinical thrombosis, this parameter was used to determine start as well as dosage of the heparin prophylaxis. Thereby, the increase of TAT complexes during a normal pregnancy without thrombolic events had to be taken in account. 43 pregnancies of 40 patients who had already suffered from thrombotic events before pregnancy or had a positive family history were monitored by this method; in none of them any thromboembolic complication occurred. Duration of treatment and maximal amount of heparin showed wide individual variations and could not be predicted by clinical criteria. However, the total dose of heparin necessary was in many patients far below of what is usually administered, thus reducing the risk of heparin-induced osteoporosis and of local allergic reactions.
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PMID:[Prevention of venous thromboembolism with heparin in risk patients during pregnancy: monitoring by measuring thrombin-antithrombin III complex]. 148 82

Within the long terminal repeat (LTR) of the human immunodeficiency virus type 1 (HIV-1) provirus there exists a steroid hormone-responsive element corresponding to the TGTTCT sequence identified as the glucocorticoid receptor binding element within the LTR of mouse mammary tumor virus. We have used an LTR(HIV-1)-chloramphenicol acetyl transferase (CAT) plasmid construct to transfect infected H9V3 and noninfected H9 cells. Four hours before harvest the cells were divided into two parts and half was treated with hydrocortisone (10(-7) M). The cells were harvested and washed, and the CAT activity was measured. In eight repeat experiments an increased expression of the CAT gene has consistently been observed in H9V3 cells in response to the glucocorticoid but no significant effect of the steroid was observed in noninfected cells. Double transfection of LTR(HIV-1)-TAT and LTR(HIV-1)-CAT into noninfected H9 cells results in a cell population in which the CAT gene was responsive to glucocorticoid stimulation. A time course and dose response for the steroid effect have been determined and the binding of steroid receptor fo the LTR-DNA characterized by gel retardation experiments.
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PMID:Regulatory elements in the human immunodeficiency virus type 1 long terminal repeat LTR (HIV-1) responsive to steroid hormone stimulation. 831 48

Functional antithrombin III levels were measured by factor Xa inhibition in 63 members of a large family with type 2 antithrombin III deficiency and individuals were classified as antithrombin III deficient or non-deficient according to the results. F1 + 2 and TAT complexes were measured using an ELISA and FPA levels were measured by radioimmunoassay. Thirty subjects (48%) were classified as antithrombin III deficient and 33 (52%) as antithrombin III non-deficient. The mean level of F1 + 2 was significantly higher in the deficient adults (0.87 +/- 0.26) compared to both the non-deficient adults (0.70 +/- 0.21) (p = 0.03) and the deficient adults receiving warfarin (0.16 +/- 0.01) (p less than 0.001). The differences in the mean values of TAT complexes and FPA between deficient and non-deficient individuals were not statistically significant. These findings suggest that untreated antithrombin III deficient subjects generate more thrombin than their non-deficient family members and that warfarin inhibits this thrombin formation. In this cross-sectional study, it is not possible to correlate the levels of the surrogate makers with future clinical outcome.
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PMID:Measurement of markers of activated coagulation in antithrombin III deficient subjects. 151 14

Medroxyprogesterone acetate (MPA), which is widely used clinically as an anticancer steroid preparation, is a very useful drug that seldom causes severe side effects such as bone marrow suppression, and can be dispensed at the outpatient clinic for an oral administration at home to the advantage of QOL. Recently however, there have been several reports suggesting its relationship with thrombosis. We measured t-PA, protein C, factor X, AT III, TAT, plasminogen, PIC, fibrinogen, and D-dimer in 11 patients with gynecologic malignancies who are treated with MPA (600 mg/day) and 11 controls. Then we examined the effects of the drug on blood coagulation and fibrinolytic activities. No changes in these parameters clearly suggested thrombogenesis in either group at this measurement or during the observation period (17 months at the maximum). The present study found no remarkable abnormalities in the blood coagulation and fibrinolytic activities. Thus, to avoid the use of MPA to patients at risk is considered to be the most important precaution for prevention of thrombosis.
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PMID:[Effect of high-dose medroxyprogesterone acetate on coagulative and fibrinolytic factors in patients with gynecological cancers]. 153 83


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