Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Similar degree (65-66%) of binding of zolpidem (0.1 microgram/ml) was found with physiological concentrations of isolated human albumin (40 g/l) or alpha-1-acid glycoprotein (1 g/l). Zolpidem binding was studied in plasma from 6 healthy subjects, 12 patients with renal failure, 12 patients with liver cirrhosis and 12 chronic uremics maintained on hemodialysis as well as in 12 serum samples from the placental cord. The unbound fraction (mean +/- s.e.m.) was 8.1 +/- 0.2% (healthy volunteers), 10.8 +/- 0.4% (renal failure), 11.3 +/- 0.7% (liver cirrhosis); 14.9 +/- 1.0% (before hemodialysis); 9.8 +/- 0.4% (after hemodialysis) and 13.2 +/- 0.9% (placental cord). All values, except those after hemodialysis, were significantly different (Dunnett's test) from those of the volunteers. Hemodialysis significantly increased the binding of zolpidem in plasma. The kinetics of protein binding of zolpidem were investigated in plasma samples from 3 healthy subjects. The average number of binding sites was 1.83 x 10(-7) mol per gram protein and the average association constant was 4.49 x 10(5) M-1.
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PMID:Plasma protein binding of zolpidem in liver and renal insufficiency. 319 98

1. alpha 1-acid glycoprotein (AAG) concentration and molecular heterogeneity, and oxprenolol protein binding were studied in serum of 15 healthy volunteers, 14 patients with lung carcinoma and 17 patients with liver cirrhosis. 2. The AAG serum concentration was increased to 180.7% in patients with lung cancer and decreased to 73.4% in cirrhotic patients as compared with controls (P less than 0.05). 3. The concanavalin A (conA) dependent heterogeneity of serum AAG was very similar in controls and patients with lung cancer: a ratio of 9/9/2 was obtained for the conA nonreactive, the conA weakly reactive and the conA strongly reactive subfraction respectively; in cirrhotic patients, the ratio shifted to 11/7/1. 4. The heterogeneity in electric charge, demonstrated by isoelectric focusing, was similar in the three groups of subjects: 70-80% of the focussed bands were found in the main three bands. 5. The binding of oxprenolol to serum proteins was increased in lung tumour patients and decreased in liver cirrhotic patients as compared with controls (P less than 0.05). There was no change in binding affinity and oxprenolol binding was significantly correlated to total AAG serum concentration and to the concentration of each of the conA dependent subtypes, in controls as well as in both patients groups.
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PMID:Alpha 1-acid glycoprotein concentration and molecular heterogeneity: relationship to oxprenolol binding in serum from healthy volunteers and patients with lung carcinoma or cirrhosis. 320 44

Serum protein binding of penbutolol, a non-cardioselective beta-blocker agent of basic nature, has been studied in healthy subjects and in patients with hepatic cirrhosis. The percentage of free penbutolol in serum containing 200 ng/ml was markedly increased in patients with hepatic cirrhosis, when compared with the group of healthy volunteers (8.17 +/- 1.13% in patients vs 3.41 +/- 0.19 in control). No significant differences in the levels of serum alpha-acid-glycoprotein (the major protein implicated in the serum binding of penbutolol) were detected. Differences in the overall affinity constant for the binding were apparent between both groups (nKa = 5.28 X 10(5) M-1 in patients vs 12.03 X 10(5) M-1 in healthy volunteers). These results suggest a qualitative change in alpha-acid-glycoprotein molecule, from hepatic patients, but further studies are needed to clarify this point.
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PMID:Serum protein binding of penbutolol in patients with hepatic cirrhosis. 324 61

Serum concentration of the aminoterminal peptide of procollagen type III (P III P) and that of the high-molecular-weight glycoprotein laminin P1 (LP1) were determined by a specific radioimmunoassay (RIA) in patients with different chronic liver diseases. Besides the routine laboratory tests, histological verification of the liver samples obtained by needle biopsy and a complex hepatitis B virus marker analysis by RIA (Biomedica-Sorin), or ELISA (Behringwerke, Marburg, FRG) kits were carried out in order to set up the correct clinical diagnosis. In normal controls, the P III P and LP1 concentrations were 7.8 +/- 1.1 ng/ml (n = 10) and 0.08 +/- 0.1 units/ml (n = 7), respectively. Patients with fatty liver (n = 25) showed a significant elevation in P III P concentration (18.6 +/- 2.7 ng/ml). Such an elevation was not unequivocally demonstrated before. In this group of patients LP1 level was also increased (1.4 +/- 0.2 units/ml, n = 10). In liver cirrhosis (n = 51) both P III P and LP1 concentrations were found to be consistently elevated.
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PMID:Determination of the aminoterminal peptide of procollagen type III and laminin P1 in serum of patients with chronic liver disease. 324 55

Alpha-1-antitrypsin is a glycoprotein of blood exhibiting the properties of a proteolytic enzymes inhibitor. It occurs in a number of polymorphic variants transmitted genetically, the differentiation of which enables to use electrophoretic methods. The authors surveys literature, involving also her own experience, on the diagnostic use of alpha-1-antitrypsin phenotypes. The variants related to alpha-1-AT deficiency are associated with an increased incidence of certain diseases: obstructive pulmonary disease, liver cirrhosis in children, cancer. An early establishment of alpha-1-antitrypsin phenotype may be significant for occupational prevention, furthermore, it may be helpful in the highlighting of etiology of certain liver diseases in early childhood.
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PMID:[Alpha 1-antitrypsin phenotypes and their role in medical diagnosis]. 332 31

Hepatic expression of sialylated difucosyl Lex antigen (SDLex, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-) was studied with monoclonal antibody FH6, which defines this structure. Hepatocytes in the severe form of chronic active hepatitis and liver cirrhosis strongly expressed SDLex. The antigen was only weakly and focally detected in chronic persistent hepatitis. The mild form of chronic active hepatitis showed intermediate expression. SDLex expressed along the liver cell membranes displayed a honeycomb pattern when extensively expressed in the severe form of chronic active hepatitis or in liver cirrhosis. Cytoplasmic expression was faint and focal. Preferential tissue distribution was at the periphery of the hepatic lobules where the distruction of the limiting plate was present. The antigen was also expressed in sinusoidal lining cells and polymorphonuclear cells but not in the biliary epithelia. Hepatocytes expressing SDLex did not express related carbohydrate antigens, ie, Type 2 chain N-acetyllactosamine, Lex, and sialylated Lea. On subcellular fractionation, the microsome fraction contained the majority of the antigen activity. SDS-PAGE and Western blot analysis revealed one major SDLex-active glycoprotein with an apparent molecular weight of 110 kilodaltons. This glycoprotein was different from SDLex-active glycoproteins found in the sera of cancer patients. No ganglioside showed FH6 reactivity. These results indicate that liver cells in active inflammatory lesion expressed a novel glycoprotein carrying SDLex antigen in honeycomblike membrane-associated pattern.
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PMID:Hepatocellular expression of a novel glycoprotein with sialylated difucosyl Lex activity in the active inflammatory lesions of chronic liver disease. 334 53

A hybridoma producing monoclonal antibody (H11) directed to lactoneotetraosylceramide (paragloboside) has been established from spleen cells of a mouse immunized with paragloboside. The monoclonal antibody H11 (immunoglobulin M type) was selected from five clones showing different reactivities with paragloboside. The monoclonal antibody was highly specific to paragloboside and lacked reactivity with other glycolipids including glucosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, and GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4Glc beta 1-1Cer. However, the monoclonal antibody (H11) was found to bind to lactosamine-containing glycolipids at their terminals, such as i- and I-type glycolipids as well as paragloboside. A two-step sandwich radioimmunoassay method for paragloboside antigen in serum was established by using the monoclonal antibody. The mean paragloboside antigen concentration in the sera from 20 normal individuals was 25.3 ng/ml. If the cutoff value was set at 80.9 ng/ml [25.3 + 2 x 27.8 (SD)], only 1 of 20 healthy controls had an elevated paragloboside value in the serum, whereas sera from 9 of 12 (75.0%) hepatoma, 4 of 10 (40%) pancreatic cancer, 16 of 40 (40.0%) stomach cancer, and 6 of 10 (60%) lung cancer patients had elevated paragloboside values. Sera from 3 of 8 hepatitis patients and 7 of 10 liver cirrhosis patients were estimated to be positive but sera from 16 patients with benign disease had paragloboside levels lower than the cutoff value. A larger amount of the antigen was found in liver metastases from colorectal carcinoma compared to the normal counterpart. The antigen was also detected in the medium of various human cancer cells and meconium. However, the antigen in the sera, medium, meconium, and cancer tissue seemed to be associated with glycoprotein or lipoprotein, because most of the antigen activity was eluted in the void volume fraction on high-performance liquid chromatography with a gel filtration column.
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PMID:Detection of patients with cancer by monoclonal antibody directed to lactoneotetraosylceramide (paragloboside). 334 24

The concentration of laminin, a high molecular weight basement membrane glycoprotein, was determined with a competitive radioimmunoassay in serum from the hepatic and cubital veins of patients with chronic liver diseases (n = 175), and correlated with portal venous pressure calculated from the hepatic vein pressure gradient. The level of laminin in the hepatic vein (mean value: 1.83 U/ml) was significantly (p less than 0.05) higher than that in the cubital vein (mean value 1.68 U/ml). In both vascular regions the glycoprotein levels increased with the degree of fibrosis, reaching their highest concentrations in cirrhosis (2.16 +/- 0.84 U/ml, p less than 0.001) (normal range: 0.81-1.43 U/ml). In all chronic liver diseases there was a significant positive correlation between the level of serum laminin and portal vein pressure (rs 0.70, p less than 0.001), which prompted us to calculate some criteria of the diagnostic validity of raised laminin for portal hypertension (portal venous pressure greater than or equal to 5 mm Hg). At a cut-off concentration of laminin of 1.45 U/ml, sensitivity is 0.87, specificity 0.74, diagnostic efficiency 0.81, and the likelihood ratio 3.4. Positive and negative predictive values at the same cut-off and at a prevalence of portal hypertension in this study of 50% are 0.77 and 0.85, respectively. Serum laminin may prove to be a potentially useful biochemical marker of portal hypertension.
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PMID:The predictive value of serum laminin for portal hypertension in chronic liver diseases. 340 6

The MCR of testosterone is decreased but the MCR of estradiol is unchanged in men with cirrhosis and elevated serum sex hormone-binding globulin (SHBG) concentrations. Previous studies indicated that SHBG from cirrhotic men selectively delivers estradiol, but not testosterone, to peripheral tissues of rats in vivo. These results suggest that estradiol and testosterone may bind to different SHBG isoforms in serum and that the estradiol-binding isoforms may be selectively altered in cirrhosis. This hypothesis was tested by polyacrylamide gel isoelectric focusing and fast protein liquid chromatography chromatofocusing. After Concanavalin-A affinity purification of serum glycoproteins from pregnant women, normal men, normal women, and cirrhotic men, the glycoprotein fraction was reconstituted, labeled with [3H]testosterone or [3H]estradiol, and applied to isoelectric focusing gels. Testosterone was bound selectively by the most acidic isoforms of SHBG, pI 4.5-5.4, and there was a significant anodal shift of the estradiol-binding isoforms in serum from cirrhotic men compared to that in serum from normal men. The selective binding of testosterone to the most acidic isoforms of SHBG was confirmed by fast protein liquid chromatography chromatofocusing, wherein the binding reactions were measured at neutral pH after separation of the isoforms. These biochemical studies and previous physiological experiments question the conventional view that testosterone and estradiol bind to a single competitive binding site on SHBG. Rather, testosterone is selectively bound by the most acidic SHBG isoforms. The estradiol-binding isoforms undergo a significant anodal shift in cirrhosis; this abnormality may result in the lack of decrease in estradiol MCR in cirrhosis.
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PMID:Differential binding of testosterone and estradiol to isoforms of sex hormone-binding globulin: selective alteration of estradiol binding in cirrhosis. 341 44

The metabolism and disposition of buspirone have been studied in the rat, the monkey, and in more than 150 human subjects. Buspirone is well absorbed, but is subject to first-pass metabolism. The mean systemic availability is approximately 4 percent. Buspirone is eliminated primarily by oxidative metabolism, which produces several hydroxylated metabolites, including 5-hydroxy-buspirone and 1-pyrimidinylpiperazine. The latter metabolite is from 1 to 20 percent as potent as buspirone in a variety of pharmacologic tests; 5-hydroxybuspirone is essentially inactive. In humans, the systemic exposure to buspirone increases linearly in relation to the oral dose. Food increases the bioavailability of buspirone by decreasing first-pass metabolism; absorption is not markedly altered. The pharmacokinetics of buspirone were not significantly different in men and women or in individuals 21 to 40 years old compared with those over 65 years of age. Half-life values observed in healthy volunteers ranged from two to 33 hours. Mean half-life values observed in healthy volunteers in the 14 studies conducted to date ranged from 2 +/- 1 to 11 +/- 3 hours. The half-life in women tended to be slightly longer than in men, but the difference was not significant. Hepatic cirrhosis resulted in a marked decrease in the clearance of buspirone, which correlated with serum alkaline phosphatase activity. Renal disease produced a modest decrease in buspirone clearance, which could not be correlated with an objective clinical measurement reflecting the severity of renal impairment. Buspirone was not removed by hemodialysis. Buspirone is highly protein bound (more than 95 percent), interacting with both albumin and alpha-acid glycoprotein. However, buspirone did not displace dilantin, propranolol, digoxin, or warfarin from plasma proteins. In rats, buspirone neither inhibited nor induced hepatic mixed-function oxidases. Co-administration of buspirone with amitriptyline or diazepam did not alter the disposition of these agents or their demethylated metabolites.
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PMID:Metabolism and disposition of buspirone. 351 29


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