Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whereas glucocorticoids induce TAT, TRP, GPT in liver and only TAT in HTC cells, no hormonal effect on the synthesis of these enzymes was found in Zajdela hepatoma cells grown in vivo as an ascitic tumor, or in vitro as layer cultures. Although these cells remain uninducible, the hormone penetrates normally, but a strong decrease of the specific binding of cytosol and nuclear proteins with the hormone was observed. The impairment at the level of the hormone receptors could account for the non-inducibility of enzyme synthesis in ZHC cells.
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PMID:Impairment of enzyme induction by glucocorticoids in Zajdela hepatoma cells. 1 35

In this study, we evaluated the role of proteolytic enzymes belonging to the coagulation, fibrinolytic, and plasma contact systems in the early postoperative phase after orthotopic liver transplantation (OLT). Twenty-nine patients were studied at the time of OLT and during the first 2 postoperative weeks. Blood samples were collected daily after OLT and analyzed for kallikrein-like activity (KK), functional kallikrein inhibition (KKI), plasmin-like activity (PL), and alpha2-antiplasmin (AP). In addition, prekallikrein (PKK), prothrombin (PTH), antithrombin III (AT III), plasminogen (PLG), prothrombin/antithrombin III complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and plasmin/alpha2-antiplasmin complexes (PAP) were measured. Nineteen patients experienced biopsy-verified acute rejections (AR) and ten patients had uneventful courses and served as controls. Plasma analyses showed that the contact, coagulation, and fibrinolytic systems were activated during OLT. Following OLT, continuous thrombin and plasmin generation was observed, and these effects were more pronounced in the group having an uneventful course than in patients with AR. Factors that could possibly affect plasma proteolytic activity, such as blood product usage during and after OLT and cold ischemia time of the liver graft, did not differ between the groups, nor did the routine liver function tests, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
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PMID:Plasma proteolytic activity in liver transplant rejection. 1036 91

A 66-year-old male was admitted to our hospital, presenting a high fever and generalized erythema on June 9, 1999. Physical examination revealed many eschars on his legs. Laboratory examinations were as follows: platelet counts, 5.5 x 10(4)/microliter: FDP, 25 micrograms/ml: TAT, 70.9 ng/ml: GOT, 177 IU/l, GPT, 174 IU/l: CRP, 32.3 mg/dl. Based on these findings, he was diagnosed as having rickettsiosis with DIC, and minocycline (200 mg/day) and heparin were started immediately, but had no clinical effect for 3 days. Blood gas analysis showed severe hypoxia and the chest CT scan revealed increased CT value in all lung fields with reticular shadows in the lower fields and pleural effusion, suggested interstitial pneumonia. Methyl-prednisolone pulse therapy was started on June 12, after which he completely recovered. Anti-Rikettia japonica IgM antibody was found to be x8,192 by immunofluorescent test, establishing the diagnosis of Japanese spotted fever. Acute respiratory failure with interstitial pneumonia shadows should be emphasized as a complication of severe rickettsiosis.
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PMID:[Japanese spotted fever complicated by acute respiratory failure]. 1074 Oct 8

The activity of the enzymes involved in aminoacid metabolism (tyrosine aminotransferase, TAT, tryptophan pyrrolase TP, serine dehydratase, SD) with rapid response to glucocorticoids and enzymes requiring for activity increase repeated administration of corticosterone (alanine aminotransferase, ALT, aspartate aminotransferase, AST) in liver, the changes of lipolysis in adipose tissue and the plasma corticosterone levels were studied in rats subjected to space flight (F), in animals from synchron model experiments (SM, simulated conditions of space flight in laboratory) and in intact controls (C). The increase of plasma corticosterone concentration and of the activity of rapidly (TAT, TP, SD) and slowly activating enzymes (ALT, AST) was found in F group 6-10 hr after space flight (18.5 days on biosatellite COSMOS 1129). This suggested the presence of acute-stress (associated primarily with the landing) and chronic stress induced hypercorticosteronemia during the flight. After the short 6-day period of recovery the plasma corticosterone concentrations and the activities of liver enzymes returned to control levels. The exposition of animals to repeated immobilization stress showed higher response of corticosterone levels in flight rats as compared to intact controls. No changes in basal lipolysis were observed in flight rats in comparison to intact controls, however the stimulation of lipolysis by norepinephrine was lower in animals from F and SM groups. This lower response of lipolytic processes to norepinephrine was found in flight animals also after six days period of recovery. These results showed that there are important changes in the regulation of lipolytic processes in adipose tissue of rats after space flight and in the conditions of model experiments.
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PMID:Metabolic changes in the animals subjected to space flight. 1154 92

To combine the advantage of poly(ethylene gylcol) (PEG) for longer circulation and cell-penetrating peptides (CPPs) for efficient cellular uptake, paclitaxel (PTX)-loaded liposomes functionalized with TAT, the most frequently used CPP, and cleavable PEG via a redox-responsive disulfide linker (PTX-C-TAT-LP) were successfully developed here. Under physiological conditions, TAT was shielded by PEG layer and liposomes exhibited a long blood circulation. At tumor site, PEG could be detached in the presence of exogenous reducing agent [glutathione (GSH)] and TAT was exposed to facilitate cell internalization. In the presence of GSH, the liposomal vesicle C-TAT-LP showed increased cellular uptake and improved three-dimensional tumor spheroids penetration in vitro compared with analogous stable shielded liposomes. C-TAT-LP achieved enhanced tumor distribution and demonstrated superior delivery efficiency in vivo. PTX-C-TAT-LP with GSH strongly inhibited the proliferation of murine melanoma B16F1 tumor cells in vitro and in vivo with the tumor inhibition rate being 69.4% on B16F1-bearing mice. In addition, the serum aspartate transaminase level, alanine transaminase level, and creatine kinase level were almost completely within normal range in the PTX-C-TAT-LP with GSH group, revealing PTX-C-TAT-LP with GSH had no obvious drug-related adverse events for liver and heart. Taken together, C-TAT-LP is a promising tumor-targeting drug carrier.
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PMID:Tumor-targeted paclitaxel delivery and enhanced penetration using TAT-decorated liposomes comprising redox-responsive poly(ethylene glycol). 2544 9

Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes. The present study was set up to test the potential involvement of hemichannels composed of connexin32 and connexin43 in acute hepatotoxicity induced by acetaminophen. Prior to this, in vitro testing was performed to confirm the specificity and efficacy of TAT-Gap24 and TAT-Gap19 in blocking connexin32 and connexin43 hemichannels, respectively. Subsequently, mice were overdosed with acetaminophen followed by treatment with TAT-Gap24 or TAT-Gap19 or a combination of both after 1.5h. Sampling was performed 3, 6, 24 and 48h following acetaminophen administration. Evaluation of the effects of connexin hemichannel inhibition was based on a series of clinically relevant read-outs, measurement of inflammatory cytokines and oxidative stress. Subsequent treatment of acetaminophen-overdosed mice with TAT-Gap19 only marginally affected liver injury. In contrast, a significant reduction in serum alanine aminotransferase activity was found upon administration of TAT-Gap24 to intoxicated animals. Furthermore, co-treatment of acetaminophen-overdosed mice with both peptides revealed an additive effect as even lower serum alanine aminotransferase activity was observed. Blocking of connexin32 or connexin43 hemichannels individually was found to decrease serum quantities of pro-inflammatory cytokines, while no effects were observed on the occurrence of hepatic oxidative stress. This study shows for the first time a role for connexin hemichannels in acetaminophen-induced acute liver failure.
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PMID:Connexin hemichannel inhibition reduces acetaminophen-induced liver injury in mice. 2868 53