Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The receptor for hepatocyte growth factor (HGF) is a transmembrane tyrosine kinase that is encoded by the proto-oncogene c-met. Recently, c-MET was detected in Reed-Sternberg (RS) cells from Epstein-Barr virus-positive (EBV(+)) Hodgkin disease (HD). The c-MET, EBER-1, and LMP-1 expression in 45 lymph node biopsies and 12 bone marrow biopsies obtained from patients with HD was analyzed. In addition, HGF levels in serum samples from 80 healthy individuals and 135 HD patients in different phases of disease. In all 45 lymph node and 12 bone marrow samples examined, RS cells expressed c-MET but not HGF(+). These results were independent of the EBV infection. Interestingly, several HGF(+) dendritic-reticulum cells were found scattered around c-MET(+) RS cells. The mean +/- SEM serum HGF levels in HD patients at diagnosis and at the time of relapse were 1403 +/- 91 (95% confidence interval [CI], 1221-1585) and 1497 +/- 242 pg/mL (95% CI, 977-2017), respectively. HGF values were significantly higher than those of healthy individuals (665 +/- 28 pg/mL; 95% CI, 600-721; and P <.001 for both groups of patients) and of HD patients in remission (616 +/- 49 pg/mL; 95% CI, 517-714; and P <.001 for both groups of patients). A significant correlation was found between serum HGF levels and B symptoms at diagnosis (P =.014). In conclusion, this study indicates that HGF and c-MET constitute an additional signaling pathway between RS cells and the reactive cellular background, thereby affecting adhesion, proliferation, and survival of RS cells. Furthermore, the serum concentration of HGF in HD patients may be a useful tool in monitoring the status of disease.
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PMID:Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease. 1115 38

1DNA topoisomerase II (topo II) is a nuclear enzyme that modifies DNA topology and also serves as a target to mediate the cytotoxicity of several antineoplastic agents. Several reports have demonstrated that a reduction of topo II is associated with reduced sensitivity to these agents. Topo II exists as two isoforms in mammalian cells: topo IIalpha and topo IIbeta. In MCF-7 cells, the half-life (mean +/- SEM) values of topo IIalpha and topo IIbeta in situ were 6.6 +/- 0.3 and 17.6 +/- 2.3 hr, respectively, as determined by [(35)S]methionine/cysteine pulse-chase analysis. Degradation of topo IIalpha in situ was abrogated by the presence of proteasome inhibitors, and the relative activities were carbobenzoxy-leucyl-leucyl-leucinal (MG132) > carbobenzoxy-leucyl-leucyl-norvalinal (MG115) > ALLN congruent with lactacystin. ATP-dependent degradation of topo IIalpha, but not topo IIbeta, was observed in extracts of asynchronously dividing HeLa and MCF-7 cells. Furthermore, degradation of topo IIalpha was abrogated by the proteasome inhibitors MG132 and MG115, but not by lactacystin, in extracts of asynchronously dividing MCF-7 cells. Finally, degradation of topo IIalpha, but not topo IIbeta, was observed to occur in a cell cycle-dependent fashion, in extracts of synchronized HeLa cells, with maximal loss of the alpha isoform occurring 2 hr after release from mitotic arrest. This degradation of topo IIalpha appeared to be facilitated by an ATP-dependent activity. Furthermore, high molecular weight bands (>200 kDa), which may represent polyubiquitinated-topo IIalpha conjugates, were also detected in extracts of synchronized HeLa cells. This study provides evidence for a role of the ubiquitin-proteasome pathway in the cell cycle-dependent regulation of topo IIalpha expression.
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PMID:Role of proteasomal degradation in the cell cycle-dependent regulation of DNA topoisomerase IIalpha expression. 1127 64

Ruminal escape of various amounts of methionine hydroxy analog [D,L-2-hydroxy-4-(methylthio)-butanoic acid (HMB)] was measured in an experiment designed as a 4 x 4 Latin square using four lactating dairy cows with cannula in the rumen and duodenum. The cows were fed a diet composed of corn silage, alfalfa haylage, rolled barley grain, canola meal, and blood meal, three times per day. The cows were fed the liquid analog each day for 1 wk before the experiment was started. On the day of the experiment, each cow received an intraruminal bolus dose of 0, 25, or 50 g of the liquid analog (Alimet feed supplement, 88% HMB) or 51.2 g of a dry calcium salt of the analog (86% HMB; MHA) mixed with 0.5 kg of ground barley grain. A liquid phase marker (Co-EDTA) was administered as a bolus dose into the rumen at the time of administration of the methionine hydroxy analogs. Rumen and duodenal contents, and blood serum were collected at 0, 1, 3, 6, 9, 12, and 24 h relative to the time of dosing. Rumen and duodenal samples were analyzed for Co and HMB, and serum was analyzed for free methionine. Fractional rate constants for the passage of the liquid marker (k(p)) and the decline of HMB concentration in the rumen (k(rHMB)) were determined by nonlinear regression. Liquid passage from the rumen was similar among the four analog treatments (0.136 +/- 0.012/h; mean +/- SEM). Ruminal escape of HMB as a percentage of the dose (100% x k(p)/k(rHMB)) did not differ between cows receiving 25, 50, and 51.2 g of the methionine analogs (42.5, 41.0, and 34.9 +/- 9.0%, respectively) and averaged 39.5%. Duodenal appearance of HMB as a percentage also did not differ between cows receiving 25, 50, and 51.2 g of the methionine analogs (16.2, 26.8, and 22.7%, respectively) and averaged 22%. Omasal absorption of HMB was variable ranging from 12.3 to 26.3% and averaged 17.6%. Serum methionine concentration peaked at 3 and 6 h after dosing and increased in proportion to the amount of the analog administered. It was concluded that 39.5% of the methionine hydroxy analog escaped rumen degradation, the percentage of the dose that escaped the rumen was not affected by the amount or form of the methionine analog fed, and the analog that escaped ruminal degradation was likely absorbed and metabolized to methionine.
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PMID:Rumen degradation and availability of various amounts of liquid methionine hydroxy analog in lactating dairy cows. 1201 38

Disturbances of the methionine cycle may result in liver injury. Patients with alcohol-induced liver disease often exhibit hypermethioninemia and a delayed clearance (CL) of methionine, but the extent to which transsulfuration and remethylation pathways of the cyclic methionine metabolism are affected is unknown. Methionine turnover was determined in 7 healthy volunteers and 6 patients with alcohol-induced cirrhosis after oral administration of 2 mg/kg [(2)H(3)-methyl-1-(13)C]methionine, which permitted us to follow transsulfuration by its decarboxylation to (13)CO(2) and remethylation by replacement of the labeled methyl group by an unlabeled one. Basal plasma concentrations of endogenous methionine (50 +/- 5 vs. 25 +/- 2 micromol/L, mean +/- SEM, P <.001) were significantly higher in patients with cirrhosis and its CL was significantly decreased (774 +/- 103 vs. 2,050 +/- 141 mL/min, P <.001). Methionine turnover amounted to 42 +/- 4 vs. 27 +/- 3 micromol/kg/h (P <.05) in controls and patients with cirrhosis, respectively. The fraction of administered methionine undergoing remethylation was lower in patients with cirrhosis (7.6 +/- 1.5 vs. 14.1 +/- 1.1%, P <.005). However, because of the larger pool of circulating methionine, the total flux of methionine through the remethylation pathway was similar in both groups. A significantly lower fraction of the administered dose appeared in the form of (13)CO(2) in breath in patients with cirrhosis (2.2 +/- 0.4 vs. 11.0 +/- 0.8%, P <.001). In conclusion, the data indicate that the liver with cirrhosis compensates for a decreased activity of remethylating enzymes by operating at higher concentrations of methionine. In contrast, transsulfuration is impaired in patients with alcohol-induced cirrhosis such that an assessment of transsulfuration by a simple breath test may provide a clinically useful estimate of hepatic function.
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PMID:Remethylation and transsulfuration of methionine in cirrhosis: studies with L-[H3-methyl-1-C]methionine. 1239 29

The objective of the present study was to examine the effect of signalment, body size and diet on plasma taurine and whole blood taurine concentrations. A total of 131 normal dogs consuming commercially prepared dog food had blood drawn 3-5 h post-prandially to be analysed for plasma amino acids and whole blood taurine. Body weight and morphometric measurements of each dog were taken. Plasma and whole blood taurine concentrations were 77 +/- 2.1 nmol/ml (mean +/- SEM) and 266 +/- 5.1 nmol/ml (mean +/- SEM), respectively. No effect of age, sex, body weight, body size, or diet was seen on plasma and whole blood taurine concentrations. Mean whole blood taurine concentrations were lower in dogs fed diets containing whole grain rice, rice bran or barley. The lowest whole blood concentrations were seen in dogs fed lamb or lamb meal and rice diets. Plasma methionine and cysteine concentrations were lower in dogs fed diets with animal meals or turkey, and whole grain rice, rice bran or barley. Fifteen of 131 dogs had plasma taurine concentrations lower than, or equal, to the previously reported lowest mean food-deprived plasma taurine concentration in normal dogs of 49 +/- 5 nmol/ml (mean +/- SEM) (Elliott et al., 2000). These findings support the theory that taurine deficiency in dogs may be related to the consumption of certain dietary ingredients. Scientific and clinical evidence supports the hypothesis that dilated cardiomyopathy is associated with low blood taurine concentration in dogs; therefore, further work is indicated to determine the mechanism by which diet can affect taurine status in dogs.
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PMID:Plasma and whole blood taurine in normal dogs of varying size fed commercially prepared food. 1275 30

The purpose of this study was to examine the effectiveness of self-etching primer in adhering 4-META/MMA-TBB resin to bovine enamel. In this study, we designed an original self-etching primer which contained an aqueous mixture of 4-MET, 35 wt% HEMA, and ferric chloride. The polished bovine enamel surface was treated with self-etching primer for 30 seconds. Tensile bond strength of 4-META/MMA-TBB resin to enamel was measured after 1-day immersion in water at 37 degrees C. The self-etching primer containing 30 wt% 4-MET and 35 wt% HEMA (4MET30) gave a significantly higher bond strength of 11.2+/-2.8 MPa than other self-etching primers. The addition of ferric chloride into 4MET30 primer significantly decreased tensile bond strength. SEM observation revealed that 4MET30 treatment produced no distinct dissolution on enamel. When compared with phosphoric acid etching, the self-etching primer containing 30 wt% 4-MET and 35 wt% HEMA was more superior in adhering 4-META/MMA-TBB resin to enamel.
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PMID:Tensile bond strength of 4-META/MMA-TBB resin to ground bovine enamel using a self-etching primer. 1551 Aug 53

This study was undertaken to determine how, and where, 2-hydroxy-4-methylthiobutyrate (HMTBA) can augment Met metabolism in lambs. Four lambs (initial body weight of 50 kg, SE = 2, and 6 mo of age) prepared with catheters in the mesenteric, portal, hepatic, and jugular veins plus the aorta, were fed at 1.5x maintenance on a grass hay, barley, fish meal, molasses/pre-mix (5:3:1:1, as fed) diet, supplied as hourly meals. Lambs were infused for 10 h with [methyl-2H3]Met (0.11 mmol/h) in a jugular vein and p-aminohippurate into the mesenteric vein. From 1 h onwards, successive 3-h infusions of saline (control), 0.55 mg/min (3.67 micromol/min), and 4.44 mg/min (29.6 micromol/min) of HMTBA were also infused into the mesenteric vein. Plasma, sampled continuously, was collected every 20 min during the last 60 min of each infusion. All infused HMTBA was recovered at the portal vein with 25% extracted subsequently by the liver. Portal appearance of total Cys and Met was unaltered by HMTBA infusion, but net splanchnic appearance of Cys increased (0.04, 0.08, 0.23 mmol/h, SEM = 0.05), whereas Met decreased (0.14, -0.01, -0.21 mmol/h, SED = 0.05). Despite this, arterial Met increased (27.0, 30.7, 51.5 microM, SEM = 2.1) as did Met irreversible loss rate (27.6, 28.7, 40.1 micromol/h, SEM = 0.51), equivalent to 40% of the HMTBA reentering the plasma after conversion to Met. These data indicate that, in ruminants, HMTBA is probably converted to Met within peripheral tissues; that is, where the metabolic need for Met exists.
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PMID:Hepatic metabolism of 2-hydroxy-4-methylthiobutyrate in growing lambs. 1650 3

The heptapeptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is an analogue of the N-terminal fragment (4-10) of adrenocorticotropic hormone which, after intranasal application, has profound effects on learning and memory formation in rodents and humans, and also exerts marked neuroprotective effects. A clue to the molecular mechanism underlying this neurotropic action was recently given by the observation that Semax stimulates the synthesis of brain-derived neurotrophic factor (BDNF), a potent modulator of synaptic plasticity, in astrocytes cultured from rat basal forebrain. In the present study, we investigated whether Semax affects BDNF levels in rat basal forebrain upon intranasal application of the peptide. In addition, we examined whether cell membranes isolated from this brain region contained binding sites for Semax. The binding of tritium-labelled Semax was found to be time dependent, specific and reversible. Specific Semax binding required calcium ions and was characterized by a mean+/-SEM dissociation constant (KD) of 2.4+/-1.0 nm and a BMAX value of 33.5+/-7.9 fmol/mg protein. Sandwich immunoenzymatic analysis revealed that Semax applied intranasally at 50 and 250 microg/kg bodyweight resulted in a rapid increase in BDNF levels after 3 h in the basal forebrain, but not in the cerebellum. These results point to the presence of specific binding sites for Semax in the rat basal forebrain. In addition, these findings indicate that the cognitive effects exerted by Semax might be associated, at least in part, with increased BDNF protein levels in this brain region.
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PMID:Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. 1663 54

Carnitine is necessary for the transport of long-chain fatty acids across the mitochondrial membrane. Carnitine is derived from the diet and from endogenous synthesis from lysine and methionine. About 98% of the body's carnitine pool is located in skeletal muscle tissue. Skeletal muscle carnitine levels were determined in two groups of malnourished patients, eight patients with anorexia nervosa with a weight loss of 32.4% +/- 1.8 (mean +/- SEM) and six surgical patients with major gastrointestinal disorders and a weight loss of 15.2% +/- 2.7. Their hepatic and kidney functions were normal. On admission, the muscle carnitine levels were 16.9 +/- 4.0 mumol/g dry weight (mean +/- SD) for the surgical patients and 20.8 +/- 5.0 mumol/g dry weight for the anorexia nervosa patients, which corresponded to carnitine levels seen in healthy subjects. No statistical significance was found between the two groups. Total parenteral nutrition was given to the surgical patients for 2 weeks and to the anorexia nervosa patients for 3-5 weeks. No statistical difference in muscle carnitine levels was found in either group after nutritional support. These malnourished patients had no decreased muscle carnitine levels on admission and maintained them during several weeks of total parenteral nutrition.
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PMID:Carnitine levels in skeletal muscle of malnourished patients before and after total parenteral nutrition. 1683 76

Cystic fibrosis (CF) is associated with many clinical complications including steatosis for which the relation to defective CF transmembrane conductance regulator protein is unclear. Choline deficiency results in hepatic steatosis. Choline is the precursor of betaine, which donates methyl groups for remethylation of homocysteine to methionine and dimethylglycine. Previously, we have shown phospholipid malabsorption and increased plasma homocysteine in children with CF. In these studies we used normal phase HPLC with tandem mass spectrometry to determine plasma choline, betaine, and dimethylglycine in children with CF (n = 34) and healthy control children without CF (n = 15). Plasma choline, betaine, and dimethylglycine were significantly lower in children with CF (means +/- SEM, 6.48 +/- 0.35, 23.8 +/- 1.49, 1.49 +/- 0.13 mumol/L, respectively) than in children without CF (8.98 +/- 0.46, 37.3 +/- 1.84, 3.01 +/- 0.17 mumol/L, respectively). Plasma choline (r = 0.373, P = 0.007) and betaine (r = 0.399, P = 0.005) were positively related to methionine, and choline was inversely related to homocysteine (r = -0.316, P = 0.03). Choline, betaine, and dimethylglycine were all significantly and positively related to the plasma S-adenosylmethionine:S-adenosylhomocysteine (SAM:SAH) ratio (r = 0.294, r = 0.377, r = 0.442, respectively; P < 0.05). The plasma choline:betaine and betaine:dimethylglycine ratios did not differ between the children with CF and the control children, suggesting no increase in betaine synthesis, or betaine-dependent remethylation of homocysteine. These studies suggest that choline depletion may contribute to increased homocysteine in children with CF. Choline depletion and altered thiol metabolism may contribute to the clinical complications associated with CF.
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PMID:Evidence of choline depletion and reduced betaine and dimethylglycine with increased homocysteine in plasma of children with cystic fibrosis. 1685 45


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