Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To predict the nature of non-calcifying lung tumors, we performed a prospective study of 46 cases with L-[methyl 11C]methionine (MET, 24 cases) and 18F-fluorodeoxyglucose (FDG, 22 cases) using positron emission tomography (PET). Mean tumor/muscle radioactivity ratios are 5.3 +/- 2.0 (n = 14) for malignant and 1.9 +/- 0.9 (n = 10) for benign with MET (p less than 0.001), and 4.4 +/- 2.2 (n = 12) and 1.5 +/- 0.3 (n = 10), respectively, with FDG (p less than 0.001). The ratios indicate that malignant tumors have higher metabolic demand than benign lesions. Tumors less than 1 cm in diameter were difficult to accurately evaluate due to PET resolution. Compared to the diagnosis at pathology, the MET study showed a sensitivity of 93% (13/14), a specificity of 60% (6/10), and an accuracy of 79% (19/24). The FDG study showed 83% (10/12), 90% (9/10), 86% (19/22), respectively. No significant differences were observed between the two tracers. This study suggests that PET studies using either MET or FDG may be very useful for the differential diagnosis of lung tumors.
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PMID:Differential diagnosis of lung tumor with positron emission tomography: a prospective study. 226 88

Activation of the MET protooncogene by a rearrangement involving the fusion of TPR and MET specific gene sequences has been observed in a human osteosarcoma cell line (HOS) treated in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). No information has been available about the possible occurrence of this rearrangement in human tumors. To facilitate rapid screening of human cell lines and tumor samples for this specific gene rearrangement, we developed a sensitive detection method based on polymerase chain reaction (PCR) amplification of TPR-MET mRNA. cDNA was generated from cellular transcripts by using one of the PCR primers, which was then used as a template for PCR amplification of a 205-base-pair region carrying the breakpoint. An end-labeled internal probe was hybridized in solution to an aliquot of the PCR product for detecting amplification. Cells could be directly screened by the assay without prior isolation of RNA. A 205-base-pair DNA fragment characteristic of the TPR-MET rearrangement was detected in cell lines previously known to contain this altered sequence. The rearrangement was also detected at very low levels in the parental (nontransformed) cell line, HOS TE-85. A preliminary survey of cell lines derived from a variety of human tumors indicates that TPR-MET rearrangement occurred and was expressed at very low frequencies by cells from 7 of 14 tumors of nonhematopoietic origin.
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PMID:TPR-MET oncogenic rearrangement: detection by polymerase chain reaction amplification of the transcript and expression in human tumor cell lines. 230 May 59

The MET oncogene, present in the MNNG-HOS chemically transformed human cell line, is activated by a gene fusion involving sequences from chromosome 1 and chromosome 7. Activated MET can act as a dominant selectable marker for chromosome-mediated gene transfer, and several transfectant cell lines have been established using this technique. Analysis of the transgenomes within these cell lines indicates that MET activation is not simply due to a chromosome translocation, but may involve an interstitial insertion of DNA from chromosome 1, into chromosome 7, probably associated with other rearrangements. Pulse field gel analysis of two transfectants indicates that, despite the presence of complex rearrangements close to MET, chromosome 7 sequences are grossly intact over a 1-Mb region thought to contain the gene defective in cystic fibrosis.
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PMID:Analysis of the transgenome of MET transfectant cell lines reveals that MET activation is accompanied by an interstitial insertion. 230 48

The Hodgkin's lymphoma-derived cell line L540, which exhibits multiple marker chromosomes and a genotype characteristic of T-cell origin, showed expression of MET oncogene. L540 was studied by in situ hybridization for chromosomal rearrangements concerning the regions where genes for TCRA and TCRB chains, for MET oncogene, and for rRNA are located. All four genes were demonstrated to be involved in the formation of marker chromosomes. Especially remarkable was the participation of rDNA-bearing regions in two different translocations.
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PMID:Chromosomal in situ hybridization of a Hodgkin's disease-derived cell line (L540) using DNA probes for TCRA, TCRB, MET, and rRNA. 232 75

Intestinal absorption of crystalline DL-methionine (DL-MET) and DL-methionine hydroxy analog calcium (DL-HMA) were determined in a true-digestibility-balance assay using cecectomized (CEC) and sham-operated conventional (CONV) cockerels. The treatments consisted of fasted birds and birds crop-intubated (CI) with 30 g of a corn-soybean meal basal diet (16% CP) supplemented with 0, .2, or .4% of DL-MET or equimolar levels of DL-HMA. There was no detectable free D-MET or L-MET or HMA in the excreta of fasted birds or of those fed the unsupplemented basal diet. The intestinal absorption of DL-HMA was 95.9 +/- .8% (means +/- SE) for CEC and 98.8 +/- .8% for the CONV cockerels. The absorption of DL-MET was approximately 99.7 +/- .2% for the CEC and the CONV cockerels. In a second experiment procedures were developed for a bioavailability assessment by comparing the growth responses to CI and intraperitoneal-injected (IP) DL-MET or DL-HMA in chicks fed a crystalline-amino-acid diet deficient in methionine. Graded increments of pH-adjusted DL-MET or DL-HMA (in water solutions) were administered twice daily in a 7-day growth assay. Slope-ratio analysis indicated that bioavailability (+/- SE) of CI DL-HMA was 91.3 +/- 11.8% relative to the CI DL-MET on an equimolar basis. The bioavailability of CI DL-HMA was similar to that of IP DL-HMA, indicating that the intestinal absorption of DL-HMA was highly efficient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Absorption and bioavailability of DL-methionine hydroxy analog compared to DL-methionine. 233 Mar 31

In this communication we show that T cell locomotion is affected by direct interaction with neurohormones. Opioid peptides, including beta-END, MET-ENK, LEU-ENK, and related enkephalin analogues enhanced migration of human peripheral blood T lymphocytes. Activity was dependent on the peptide NH2-terminal sequence, stimulated by enkephalin analogues with specificity for classical delta or mu types of opiate receptor, and inhibited by the opiate receptor antagonist naloxone. Our studies suggest that such neuropeptides stimulate T cell chemotaxis by interaction with sites analogues to classical opiate receptors. We propose that the endogenous opioids beta-END, MET-ENK, and LEU-ENK are potent immunomodulating signals that regulate the trafficking of immune response cells.
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PMID:Neurohormones regulate T cell function. 233 33

The role of opioids, dopamine and serotonin in ethanol (EtOH) reward and preference was investigated in non-deprived, Alcohol-Preferring (P), and genetically heterogenous Wistar rats. Operant responding for ethanol was initiated using sweet-solution substitution procedures. The rats were then trained in 30-min daily sessions to respond for ethanol (10% v/v) versus water under a two-lever, free-choice contingency. All testing was conducted in the absence of water and food deprivation or addition of sweeteners to the ethanol drinking solution. Rats of both strains developed stable preferences in responding for ethanol over water and consumed ethanol at quantities sufficient to produce pharmacologically relevant mean blood alcohol concentrations (P-Rats: 98 +/- 19.6 mg%; unselected Wistars: 41.7 +/- 8.5 mg%). In P-rats, systemic naloxone (NAL; 0.125, 0.25 and 0.5 mg/kg) pretreatments resulted in a dose-dependent suppression in responding for both ethanol and water, but did not alter ethanol preference (expressed as percent ethanol of total intake). In contrast, bromocriptine (BRO; 1.0, 2.0 and 4.0 mg/kg) produced a significant, dose-dependent shift in preference from ethanol toward water by inhibiting responding for ethanol while enhancing water consumption. In unselected Wistar rats, NAL and BRO treatments produced changes in ethanol preference patterns similar to those observed in P-rats. However, compared to P-rats, these changes were smaller and not consistently dose dependent. No changes in ethanol preference and water or ethanol intake were observed with methysergide (MET; 2.5, 5.0, 10.0 mg/kg) in either strain of rat. Together, the results suggest a possible involvement of dopaminergic mechanisms in the reinforcing properties of ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free-choice responding for ethanol versus water in alcohol preferring (P) and unselected Wistar rats is differentially modified by naloxone, bromocriptine, and methysergide. 234 59

We have measured the content of enkephalin-containing peptides (ENK-containing peptides) in adrenal gland extracts from fetal sheep between 68-142 days gestation and from adult sheep. We investigated whether there are changes in the post-translational processing of ENK-containing peptides in the fetal sheep adrenal gland with increasing gestational age. ENK-containing peptides in adrenal extracts from fetal sheep (68-142 days gestation) and adult sheep were separated using gel filtration chromatography and the ENK immunoreactivity (ENK-IR) was measured using RIAs for Met-enkephalin-Arg6,Phe7 immunoreactivity (MERF-IR) and Met-o-enk immunoreactivity (MET-O-ENK-IR). The MET-O-ENK-IR in fetal and adult sheep adrenal extracts was distributed in four main peaks, which corresponded to mol wt (MW) ranges of more than 12, 7-12, 3-7, and less than 3 kDa. There was a significant increase (P less than 0.05) in the total ENK-IR content of the fetal adrenal between 68-78 (42.4 +/- 19.2 ng/adrenal) and 100-121 (320.1 +/- 142.6 ng/adrenal) days gestation. There was also a significant increase in the proportion of MET-O-ENK-IR and MERF in the less than 3 kDa range between 68-78 (MET-O-ENK, 6.8 +/- 2.7%; MERF, 10.3 +/- 1.4%) and 100-121 (MET-O-ENK, 24.4 +/- 5.1%; MERF, 26.2 +/- 5.8%) days gestation, with an associated decrease in the ratio of ENK-containing peptides in the high MW form (i.e. greater than 3 kDa) compared to those in the low MW (less than 3 kDa) forms (10.4 +/- 2.5 at 68-78 days gestation; 4.2 +/- 1.1 at 100-121 days gestation). There was also a significant decrease in the percentage of MET-O-ENK in the 12 kDa range after 139 days gestation (125-135 days gestation, 20.4 +/- 2.2%; 139-142 days gestation, 4.0 +/- 2.1%). Therefore, there is an increase in the proportion of the low MW forms of ENK-containing peptides in the fetal sheep adrenal with advancing gestational age, which may reflect changes in the post-translational processing of the precursor proenkephalin-A during development.
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PMID:The molecular weight profile of enkephalin-containing peptides in the sheep adrenal gland changes during development. 236 76

The hips and lower extremities of four complete paraplegic male subjects (T-6, T-7, T-8, and T-11) were stimulated with functional neuromuscular stimulation (FNS) via transcutaneous intramuscular electrodes (20 mA, 0-150 pulse width, and 20 Hz). Cardiopulmonary (CP) and/or cardiovascular (CV) responses were measured during maximal (seated) arm ergometry (AE), FNS, and FNS + AE. Subjects' lower extremities were stimulated with a 2 s walking cycle via a microprocessor computer. Data were collected with a SensorMedic MMC Horizon (VO2 and VCO2 at STPD and VE at BPTS). The mean MET level (1 MET = 3.5 ml O2/kg/min) during FNS was 4.8. Mean METS during FNS + AE was 10.3 and mean METS for AE was 7.2. Mean lactic acid (LA) after FNS, AE, and FNS + AE was 73 mg percent, 77 mg percent and 115 mg percent respectively. Respiratory exchange ratio (RER) (VCO2/VO2) was greater than 1.2 during the first 2 to 5 min of FNS but decreased to less than 1.0 during the second 5 min of FNS. Steady state VO2 and RER less than 1.0 indicated a FNS transition from anaerobic to aerobic metabolism. Subject T-11 had CV limitations during FNS and FNS + AE due to excessive LA from FNS (115 mg percent). Ventilatory (VE) responses during AE, FNS, and FNS + AE were consistent with VO2; and mean maximal VE and VO2 for subjects T-6, T-7, and T-8 during FNS + AE was greater than 90 percent of that observed in sedentary normals. The aerobic and anaerobic capacities of paraplegic subjects is primarily limited by available muscle mass rather than impaired CV or CP function.
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PMID:Metabolic responses to arm ergometry and functional neuromuscular stimulation. 236 94

In order to determine the effects of large variations in plasma amino acid concentrations upon human erythrocyte amino acid content, the plasma concentration of blood samples was enhanced (x 3.8) by adding amino acids or decreased (x 0.49) by plasma dilution. Before and after incubation (30 s at 37 degrees C), the erythrocyte contents were calculated from whole blood and plasma amino acid concentrations. Large and rapid plasma concentration variations led to significant erythrocyte changes in 11 amino acids. THR, CIT, alpha AB, VAL, MET, ILE, LEU, TYR, PHE, TRP, and ARG. Relationships between erythrocyte and plasma concentrations were determined for these amino acids. These observations were examined in the light of the role played by erythrocytes in blood amino acid transport.
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PMID:The effects of changes in plasma amino acid concentrations on erythrocyte amino acid content. 237 38


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