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)

Exposure of mouse peritoneal macrophages in vitro to the nonspecific immunomodulator MER (methanol extraction residue fraction of phenol killed, acetone washed tubercle bacilli) failed to heighten their phagocytic and bacteriostatic activities toward Staphylococcus albus, even when amounts of the agent below the threshold of gross toxicity were employed. In contrast, exposure of such macrophages to supernatants of whole splenocyte suspensions that had been obtained from normal donors and were incubated with MER resulted in consistent potentiation of both phagocytosis and bacteriostasis. The findings suggest that the MER effect on macrophages function is mediated, in this system, by soluble lymphocyte product(s).
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PMID:Mouse macrophage functions under the influence of factors released by spleen cells preincubated with the methanol extraction residue (MER) tubercle bacillus fraction. 679 43

This retrospective clinical review of reports by several authors of 253 children with extrahepatic (EPH) and 87 children with intrahepatic (IPH) portal hypertension who have undergone operations for variceal hemorrhage presents the long-term follow-up based on the type of management provided. Shunt operations are preferred over direct operative procedures in patients with EPH when mesenteric veins suitable for shunting are available. Cavomesenteric shunts provide the best permanent relief from variceal bleeding. Partial esophagogastrectomy with colon interposition or poral-azygous disconnection are the best operations when a shunt is not technically feasible, almost half of the patients obtaining long-term relief from bleeding. More than one fourth of the children with EPH can be managed successfully for long periods nonoperatively. For children with variceal bleeding due to IPH, the underlying liver disease determines the prognosis. The ultimate mortality is approximately the same regardless of whether a shunt or direct procedure is performed.
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PMID:Surgical management of portal hypertension in childhood: long-term results. 696 98

The structure-activity relationships of various natural and synthetic oestrogens, anti-oestrogens and some other steroid hormones with respect to early uterine albumin accumulation (EAV) was studied in sprayed mice. The results were compared with the activity of these agents to produce a late anabolic response (LAR). The potency ranking order among the oestrogens with respect to EAV was found to be oestradiol-17 beta, greater than oestriol, greater than meso-hexoestrol, greater than erythro-deoxyhexoestrol, greater than ent-oestradiol-17 beta, greater than (-)methallenestril phenol. Generally the oestrogens were much more potent with respect to EAV than LAR. No correlation was found when the ability to promote EAV and LAR was compared. Among other agents tested for effect on the EAV, progesterone, the synthetic progestogen, DU-41165 and the anti-hormones MER-25 and U-11100A (nafoxidine) showed no effect. However, hydrocortisone diminished EAV, while dihydrotestosterone increased EAV substantially.
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PMID:Oestrogens and anti-oestrogens show dissociation between early uterine vascular responses and uterotrophic effects in mice. 720 17

Dual inhibitors of the two zinc metallopeptidases, neutral endopeptidase (NEP, EC 3.4.24.11) and angiotensin-I-converting enzyme (ACE, EC 2.4.15.1), have been the focus of much clinical interest for the treatment of hypertension and congestive heart failure. We have previously reported that compound 2 (N-[[1-[(2(S)-mercapto-3-methyl-1-oxobutyl) amino]-1-cyclopentyl]-carbonyl]-L-tyrosine) was a potent dual inhibitor in vitro (IC50 (ACE) = 7.0 nM, IC50 (NEP) = 1.5 nM) (Fink et al. J. Med. Chem. 1995, 38, 5023-5030). This compound was found to have oral activity; however, its duration of effect was short. A series of thioacetate carboxylic acid ester analogs of compound 2 was prepared. Modifications were also made to the tyrosine phenol. These compounds were evaluated for their ability to inhibit plasma ACE activity when administered orally to conscious normotensive rats. Most of the compounds prepared were found to be orally active with longer durations of effect than compound 2. Compound 38 (N-[[1-[(2(S)-(acetylthio)-3-methyl-1-oxobutyl) amino]-1-cyclopentyl]carbonyl]-O-methyl-L-tyrosine ethyl ester), administered at 11.7 mg/kg po, was found to be more efficacious than captopril at 10 mg/kg po. This compound was also found to inhibit plasma NEP activity following oral administration to conscious rats and was more efficacious than acetorphan. Compound 38 was found to lower blood pressure in the aorta-ligated rat and the spontaneously hypertensive rat when administered orally. The synthesis and biological activity of these dual inhibitors are discussed.
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PMID:Mercaptoacyl dipeptides as orally active dual inhibitors of angiotensin-converting enzyme and neutral endopeptidase. 875 37

The fundamental new universal method of evaluation of the interaction between macroradical and radioprotector (the access window method) is presented here. It's based on the modelling phenomenon of molecule penetration to the active centre of macromolecule structure through the functional groups free "window". The steric modelling of the B-DNA structure fragments allowed to measure the conformation parameters of the intermediate stereocomplex between interacting substancies. Using the thesis about molecule InH mask the interaction process of InH (steric hindered phenol 4-oxy-3,5-di-tret-butyl-alpha-metylbenzylamine, mercaptoethanol, MET, and L-cysteine, CYS) with 2-deoxyribosyl five radicals in DNA was studied. It was determined, that the radioprotection maximum effect on single-strand breakage formation in irradiated cell can reach 2/3 of the total sugar radicals yield and for MET and CYS (with minor mask squares) -87.5, and 91%, accordingly (it agrees with experiment in literature data).
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PMID:[Efficacy of radioprotectors and gene mutations following 2-deoxyribosyl damage. Computer modeling]. 1036 57

The reported estrogenic action of phenol red and/or its lipophilic contaminants has led to the widespread use of indicator-free culture medium to conduct endocrine studies in vitro. Because we have recently developed methods to measure large-magnitude estrogen effects in the tissue culture medium containing phenol red, we concluded that the indicator issue required further evaluation. To do this, we selected nine estrogen receptor positive (ER+) cell lines representing four target tissues and three species. We investigated phenol red using five different experimental protocols. First, 17beta-estradiol (E2) responsive growth of all nine ER+ cells lines was compared in the medium with and without the indicator. Second, using representative lines we asked if phenol red was mitogenic in the indicator-free medium. The dose-response effects of phenol red were compared directly to those of E2. Third, we asked if tamoxifen-inhibited growth equally in phenol red-containing and indicator-free medium. This study was based on a report indicating that antiestrogen effects should be seen only in phenol red-containing medium. Fourth, we asked if phenol red displaced the binding of 3H-E2 using ERK intact human breast cancer cells. Fifth, we compared E2 and phenol red as inducers of the progesterone receptor using a human breast cancer cell line. All the experiments presented in this report support the conclusion that the concentration of phenol red contaminants in a standard culture medium available today is not sufficient to cause estrogenic effects. In brief, our studies indicate that the real issue of how to demonstrate estrogenic effects in culture resides elsewhere than phenol red. We have found that the demonstration of sex steroid hormone-mitogenic effects in culture depends upon conditions that maximize the effects of a serum-borne inhibitor(s). When the effects of the inhibitor are optimized, the presence or absence of phenol red makes no everyday difference to the demonstration of estrogen mitogenic effects with several target cell types from diverse species.
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PMID:Estrogen mitogenic action. III. is phenol red a "red herring"? 1103 95

A solid-phase microextraction (SPME) method was developed to quantitatively determine the amount of 6-hydroxyhexanoic acid in aqueous solutions. The SPME method in combination with GC-MS was then applied to identify and quantify the low-molecular-mass compounds migrating from a new poly(vinyl chloride) (PVC) material, PVC/polycaprolactone-polycarbonate (PCL-PC) during ageing in water. It was shown that only a small amount of 6-hydroxyhexanoic acid, the final hydrolysis product of PCL-PC, migrated from the blend during ageing at 37 and 70 degrees C. If, however, the temperature was raised to 100 degrees C rapid hydrolysis of PCL-PC resulted. In addition to 6-hydroxyhexanoic acid, 6-hydroxyhexanoic acid dimer, caprolactone, different carboxylic acids, acetophenone and phenol were identified. SPME-GC-MS was also applied to monitor the low-molecular-mass compounds migrating from the PVC/PCL-PC blend during thermo-oxidation.
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PMID:Qualitative and quantitative solid-phase microextraction gas chromatographic-mass spectrometric determination of the low-molecular-mass compounds released from poly(vinyl chloride)/polycaprolactone-polycarbonate during ageing. 1450 11

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway elicits a survival signal against multiple apoptotic insults. In addition, phase II enzymes such as heme oxygenase-1 (HO-1) protect cells against diverse toxins and oxidative stress. In this work, we describe a link between these defense systems at the level of transcriptional regulation of the antioxidant enzyme HO-1. The herb-derived phenol carnosol induced HO-1 expression at both mRNA and protein levels. Luciferase reporter assays indicated that carnosol targeted the mouse ho1 promoter at two enhancer regions comprising the antioxidant response elements (AREs). Moreover, carnosol increased the nuclear levels of Nrf2, a transcription factor governing AREs. Electrophoretic mobility shift assays and luciferase reporter assays with a dominant-negative Nrf2 mutant indicated that carnosol increased the binding of Nrf2 to ARE and induced Nrf2-dependent activation of the ho1 promoter. While investigating the signaling pathways responsible for HO-1 induction, we observed that carnosol activated the ERK, p38, and JNK pathways as well as the survival pathway driven by PI3K. Inhibition of PI3K reduced the increase in Nrf2 protein levels and activation of the ho1 promoter. Expression of active PI3K-CAAX (where A is aliphatic amino acid) was sufficient to activate AREs. The use of dominant-negative mutants of protein kinase Czeta and Akt1, two kinases downstream from PI3K, demonstrated a requirement for active Akt1, but not protein kinase Czeta. Moreover, the long-term antioxidant effect of carnosol was partially blocked by PI3K or HO-1 inhibitors, further demonstrating that carnosol attenuates oxidative stress through a pathway that involves PI3K and HO-1.
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PMID:Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. 1468 81

The HER2/neu oncogene has been reported to be amplified in > 20% of invasive ductal carcinomas. In order to investigate the HER2/neu status in pure populations of breast cancer cells, a laser capture microdissection (LCM) system was used. Formalin-fixed paraffin-embedded breast tissue areas corresponding to normal ducts, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were microdissected and genomic DNA was isolated by a modified proteinase K- phenol extraction method and subjected to PCR for HER2/neu analysis. One hundred % concordance for detection of the HER2/neu gene amplification was found between immunohistochemistry and PCR used in combination with LCM. Our results indicated that LCM is a powerful technique for isolating pure populations of cells from paraffin-embedded tissue sections and that these cells can be used to study genomic alterations at the DNA level.
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PMID:Analysis of the HER2/neu gene amplification in microdissected breast cancer tumour samples. 1661 88

The removal performance of typical refractory organic compounds in landfill leachate was investigated during the electrochemical (EC) oxidation and anaerobic process combined treatment system in this paper. The results indicated that the treatment of landfill leachate by the combined system was highly effective. The toxicity of leachate was notably decreased after the electrochemical oxidation process and the biodegradability was improved. The concentration of the organic acid with low molecular weight in the leachate increased from 28% to 90% based on the biodegradability assays after the EC oxidation process. The anaerobic digestion could further remove the residual organic compounds. At a hydraulic retention time (HRT) of 16 hours and an organic loading rate (OLR) of 8 kg COD/m3 d, the concentration of COD, SS, ALK, VA, N-TKN, N-NH4+ and P-PO4(3)- [corrected] in UASB effluent were 532, 12, 6744, 400, 540, 455 and 11.6 mg/L, respectively, with approximately 90% removal efficiency of COD. The organic compounds in the landfill leachate revealed different degradation characteristics in the combined system. p-chloroaniline, bisphenol A, 6-methyl-2-phenyl-quinoline, dimethylnaphthaline and N'-(2-methyl-4-chlorophenyl)-N-cyclohexyformamidine, classified into the first group in this paper, were completely removed by the EC oxidation and did not reappear in the effluent of the UASB reactor. Phenylacetic acid, 3-methyl-indole and N-cyclohexyl-acetamide, called the second group, were completely removed, but reappeared in the UASB reactor. 4-methyl-phenol, 3,4-dihydroisoquinoline, 2(3H)-benzothiazolone, exo-2-hydroxycineole and benzothiazole, the third group, were degraded little in the EC oxidation process, but extensively removed by the anaerobic process. Benzoic acid, benzenepropanoic acid and 2-cyano-3,5-dimethyl-1-hydroxypyrrole, the fourth group, concentration obviously increased in the EC process, but was completely removed in the UASB reactor. The content of volatile fatty acids (VFAs) markedly increased from 0.68% in the leachate to 16.18% in the effluent from the electrochemical oxidation process (EC(effl)). In addition, the degradation rate of organic compounds from the landfill leachate was different in the EC oxidation and anaerobic process.
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PMID:Treatment of landfill leachate by electrochemical oxidation and anaerobic process. 1757 41


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