Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat Liver fatty acid binding protein (FABP) has been purified to homogeneity by the procedures including Sephadex G-100 and DEAE-cellulose column chromatography. FABP was resolved into two peaks of A and B by DEAE-cellulose column chromatography. Each of these fractions exhibited apparent homogeneity upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate with a molecular weight of 16,000 daltons and amino acid analysis of these fractions has revealed that they are identical protein. However, upon isoelectric focusing on polyacrylamide gel, the isoelectric (pl) points were differed considerably showing microheterogeneity. In the present investigation, one isoform (pl = 5.0) of FABP was purified by a successive DEAE-cellulose column chromatography and used for the subsequent experiments of fatty acyl-protein interactions. When the final FABP preparation was partly freed of fatty acids by a mild delipidation technique using Lipidex, the pl shifted toward higher regions of 7.0. However, the pl of the delipidated FABP turned to the original 7.0 by recombining fatty acids. On the other hand, the secondary and tertiary structures were also significantly changed by delipidization, which have been demonstrated by circular dichroism (CD) and nuclear magnetic resonance (1H-NMR) spectroscopy. Furthermore the structural properties of the delipidated FABP also could be restored by recombining fatty acid. These findings suggested that the weakly bound fatty acids are responsible for the functional capacity of the FABP by virtue of changing the protein conformation.
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PMID:[Conformational changes of rat liver fatty acid binding protein induced by long chain fatty acid]. 226 18

31P NMR was used to study the erythrocytes of three patients who exhibited a familial multisystem disease characterized by fatty liver, diabetes and nonspherocytic hemolytic anemia of unknown etiology. 31P NMR measurements disclosed an abnormally high level of intracellular inorganic phosphate (Pi) and an abnormally low level of ATP in the erythrocytes 6 h after blood withdrawal from proband (I-1). This finding suggested that ATP was markedly decreased in the red cells of this proband, as compared with those of normal subjects. Time-dependent changes of 31P NMR spectra of the erythrocytes from the two daughters (II-1, II-2) of the proband demonstrated clearly an enhanced decomposition of ATP with a concomitant increment of Pi. Several ATP-consuming enzymes in erythrocytes, such as those in the Embden-Meyerhof system, pentose phosphate pathway enzymes, Na+, K(+)-ATPase and Ca2+, Mg2(+)-ATPase, were within normal limits of activity, but Mg2(+)-ATPase was drastically above the normal limit. The Mg2(+)-ATPase activity was 3 times higher in the red cell membranes of these patients than in those from normal subjects.
NMR Biomed 1989 Sep
PMID:An interesting syndrome of hemolytic anemia, degeneration of the liver and diabetes associated with a high red cell Mg-ATPase, detected by 31P NMR spectroscopy. 253 4

In evaluating nuclear magnetic tomography for the diagnosis of liver disease, one must differentiate between circumscribed and diffuse lesions. Nuclear magnetic tomography provides additional information for lesions which are echogenic on ultrasound and can differentiate between metastases, haemangiomas and hamartomas. In diffuse parenchymal disease measurement of relaxation time can differentiate between fatty liver, cirrhosis (alcoholic, primary biliary), haemochromatosis (cirrhotic transformation) and hepatoma. NMR spectroscopy is a method for the future.
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PMID:[Differential diagnosis of liver diseases in the nuclear spin tomogram]. 298 31

This review includes the initial experience with NMR imaging of the liver, spleen, and pancreas at the University of California, San Francisco, using a prototype 0.35 Tesla system. This experience shows great promise for detection of hepatic metastases using T1-weighted pulse sequences. T2-weighted pulse sequences appear sensitive for detecting cavernous hemangioma of the liver and may allow tissue specific discrimination of the benign lesion from cancer. NMR is also suitable for evaluating diffuse metabolic alterations and is sensitive and specific for the diagnosis of iron overload. Detection of fatty liver requires use of chemical shift techniques as conventional NMR imaging pulse sequences are relatively insensitive. Motion artifacts and lack of an effective bowel contrast agent limits imaging of the pancreas and retroperitoneum, where CT remains the procedure of choice. The normal spleen has longer T1 and T2 relaxation times than liver or pancreas and NMR has not been successful in diagnosing splenic metastases or lymphoma on a routine basis. We conclude that NMR imaging will be valuable in the diagnosis of focal liver disorders; until fast scan techniques and effective magnetic contrast agents are available for oral and/or intravenous use, other abdominal applications will remain limited.
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PMID:Nuclear magnetic resonance of the liver, spleen, and pancreas. 300 15

In an effort to determine if NMR techniques might be used to detect TPN-induced hepatic steatosis, the NMR spin-lattice (T1) and spin-spin (T2) relaxation times were measured on liver tissue from rats who received one of five dietary regimens: (1) 100% of nonprotein calories as lipid (Fat); (2) a mixture of 50% lipid and 50% glucose nonprotein calories (50/50); (3) 100% of nonprotein calories as glucose (CHO); (4) intravenous saline and standard laboratory rat chow (Saline); and (5) rat chow alone (Oral). The parenteral diets were isonitrogenous and isocaloric. Serum liver function tests were also measured. Animals in the Fat and 50/50 groups had the greatest amounts of liver fat and significantly longer T1 and T2 times (p less than 0.01) than any other group. Furthermore, the correlation of T2 time with liver fat content (r = 0.82) was far superior (p less than 0.001) to that of serum SGPT (r = 0.48) which was the only liver function test which correlated significantly with liver fat content. In a multiple linear regression analysis, T1 and T2 predicted liver fat content with an r value of 0.84 (p less than 0.001). These data suggest that in vivo NMR imaging techniques might be used to detect TPN-induced fatty infiltration of the liver noninvasively.
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PMID:Detection of total parenteral nutrition-induced fatty liver infiltration in the rat by in vitro proton nuclear magnetic resonance. 308 30

To determine if NMR techniques might be used to detect hepatic steatosis secondary to protein malnutrition, the T1 and T2 relaxation times of liver tissue from rats subjected to long-term protein malnutrition were measured in vitro. The liver tissue from rats fed a protein-deficient rat chow (PD) for 37 days (N = 9) was characterized by increased proportion of fat (P less than 0.001) but decreased water and nitrogen contents (P less than 0.001) relative to controls (N = 9). Mean T1 times were significantly shorter and T2 times significantly longer in liver tissue from protein-depleted animals (P less than 0.001). There was no overlap of T2 times between the protein-depleted and control animals. The consistent changes in T2 that occur with fatty infiltration of the liver should be detectable by current NMR imagers.
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PMID:In vitro detection of fatty liver infiltration in protein-depleted rats using proton nuclear magnetic resonance. 401 Feb 73

Spatially localized 31P NMR spectroscopy was used to assay in vivo the liver of intact rats fed orotic acid (OA) in a diet which produces hepatic steatosis. Twenty-three sets of multiple volume spectra were obtained from twenty-one 265- to 315-g female rats after 0-9 days of feeding either a 1% OA/64% sucrose diet (12 rats) or a 65% sucrose control diet (9 rats). The intensity of the in vivo diphosphodiester resonance ascribed to UDP-hexos(amin)es increased and the phosphomonoester resonance decreased in intensity prior to fatty infiltration. High resolution NMR spectroscopy of extracts of these livers indicated that the UDP-hexos(amin)e peak included four different UDP-sugars including UDP-N-acetylglucosamine (UDP-glcNAc), and that lower phosphocholine (P-Cho) accounted for the lower phosphomonoester resonance in vivo. Increased UDP-glcNAc is thought to reflect impaired lipoprotein glycosylation as a mechanism for hepatic steatosis in orotic acid feeding. P-Cho deficiency has been shown to be due to an increased rate of phosphatidylcholine synthesis. Low P-Cho concentration has been shown to be associated with lipid accumulation in a choline-deficient diet, but was not previously associated with hepatic steatosis in OA feeding. Changes in phosphorus metabolites were observed 2 days prior to development of fatty liver. HPLC assay of uridine nucleotides showed a good correlation between magnetic resonance spectroscopy and HPLC quantitation. In this study there were two biochemical correlates of impaired hepatic lipid secretion detectable by in vivo assay with 31P NMR spectroscopy. This method has application for noninvasive assays in ornithine transcarbamylase-deficient patients.
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PMID:An in vivo 31P magnetic resonance spectroscopy study of uridine excess in rats fed orotic acid. 755 16

Lipid extracts of biopsy samples from normal and non-alcohol-induced fatty human liver were studied by 1H-NMR at 200 MHz. Spectra of the lipid extracts from 10 mg samples were obtained in 6 min with routine acquisition parameters and allowed the calculation of the phosphatidylcholine to total fatty acyl chain ratio, the cholesterol to total fatty acyl chain ratio, the average fatty acyl chain length, the unsaturation ratio and the acylated glycerol to total fatty acyl chain ratio. The data suggest that lipids with a higher ratio of de novo synthesized fatty acyl chains are stored in non-alcohol-induced fatty liver. NMR lipid analysis appears to be a reliable method for the rapid assessment of hepatic lipid composition on bioptic specimens.
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PMID:1H NMR spectroscopic studies of lipid extracts from human fatty liver. 850 93

We report here the combined application of (1)H magic angle spinning (MAS) and high-resolution NMR spectroscopy and pattern recognition methods to study the effects of a model toxin (D-galactosamine) in liver spheroid cultures. (1)H NMR spectra of metabolic profiles of spheroids showed closer similarities to intact liver spectra than those of isolated hepatocytes, suggesting their superiority as an in vitro model system. Batches of spheroids were prepared from male Sprague Dawley rat livers and incubated in control hepatocyte medium or medium containing D-galactosamine (4 or 20 mM) for 4 or 24 h. Intact spheroids were packed into rotors and analyzed using MAS-NMR spectroscopy or homogenized and analyzed using conventional (1)H NMR spectroscopy. Principal components analysis, (PCA), of the NMR data revealed separation of control and D-galactosamine-treated spheroids based on changes in the concentrations of the triglycerides and elevations in cholesterol and esters. The absence of cholesterol in hepatocytes and the relative under-representation of the lipid resonances offer an important advantage of spheroids over hepatocytes for the (1)H NMR studies of fatty liver. Orthogonal signal correction (OSC) was used as a data filter to remove non-dose-dependent variation from the NMR spectra, improving the classification of treated spheroids and controls. This work shows that useful metabolic information can be obtained on drug toxicity by the use of combined MAS-NMR and high-resolution NMR of liver spheroids and that such studies may enhance the validation of in vitro techniques against in vivo models for metabolic profiling.
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PMID:Metabolic profiling of the effects of D-galactosamine in liver spheroids using (1)H NMR and MAS-NMR spectroscopy. 1243 25

Hypercreatinuria is a well-known feature of liver and testicular toxicity and we have recently proposed that hepatotoxin-induced hypercreatinuria would arise as a consequence of increased cysteine synthesis associated with the provision of protective substances (glutathione and/or taurine). Here a direct relationship between hepatotoxin-induced hypercreatinaemia and hypercreatinuria is shown and the possible relationships of hepatotoxin-induced hypercreatinaemia and hypercreatinuria to hepatic damage and to weakened nutritional status are examined. Male Sprague-Dawley rats were dosed with a variety of model hepatotoxins at two dose levels per toxin. Blood plasma samples taken at 24 h post-dosing and urine samples collected from 24-31 h post-dosing were analysed by (1)H NMR spectroscopy. Both hypercreatinaemia and hypercreatinuria were found in rats dosed with allyl formate (75 mg/kg), chlorpromazine (30 and 60 mg/kg), alpha-naphthylisothiocyanate (ANIT, 100 mg/kg) and thioacetamide (200 mg/kg), whilst significant hypercreatinuria, but not hypercreatinaemia, was found after dosing with thioacetamide (50 mg/kg). Neither hypercreatinaemia nor hypercreatinuria were found after dosing with allyl formate (25 mg/kg), ethionine (300 and 1000 mg/kg) or ANIT (30 mg/kg). Reduced feeding is known to cause hypercreatinuria in rats and, of the four hepatotoxins that induced hypercreatinaemia and hypercreatinuria at the given time-points, two, chlorpromazine and ANIT, also affected nutritional status with ketosis being clearly identifiable from the plasma (1)H NMR spectra. Thus, the creatine changes induced by ANIT and chlorpromazine are potentially attributable, in whole or in part, to reduced feeding rather than to liver effects alone and, consequently, the results were examined with and without inclusion of the ANIT and chlorpromazine data. With all of the data included, there were eight out of ten points of correspondence between the incidence of hypercreatinaemia and/or hypercreatinuria and the incidence of increases in plasma alanine aminotransferase (ALT) activity. At the same time there were nine out of ten points of correspondence between the incidence of hypercreatinaemia and/or hypercreatinuria and the incidence of increases in plasma aspartate aminotransferase (AST) activity. However, with the ANIT and chlorpromazine data excluded there was complete (six out of six points) correspondence between the incidence of hypercreatinaemia and/or hypercreatinuria and the incidence of increases in plasma AST and ALT in the remaining data. Likewise, with all of the data included, there was some apparent correlation (correlation coefficient, r=0.80) between the group mean levels of plasma AST and plasma creatine when expressed relative to the mean values for controls sampled at the same time-point. However, with the ANIT and chlorpromazine data excluded, that correlation coefficient was increased to 0.95. The findings of these studies suggest that the ANIT- and chlorpromazine-induced creatine changes may have been caused by reduced feeding rather than by liver toxicity. The allyl formate and thioacetamide data indicate that hepatocellular necrosis is accompanied by increases in plasma and urinary creatine, and suggest the possibility of a quantitative relationship between the increases in plasma AST and the increases in plasma creatine that are associated with hepatocellular necrosis. The ethionine and ANIT data suggest that fatty liver (steatosis) and cholestatic damage may not be associated with hypercreatinaemia and hypercreatinuria.
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PMID:Hepatotoxin-induced hypercreatinaemia and hypercreatinuria: their relationship to one another, to liver damage and to weakened nutritional status. 1452 May 8


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