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

Serum ferritin concentrations were found to be raised, often considerably, in 58 of 76 black patients with primary liver cancer (PLC). No correlation could be demonstrated between the serum ferritin concentration and several other measurements, including the following: hepatic iron stores measured chemically, the size of the tumour, serum transaminase values, and the presence or absence of cirrhosis in the non-tumorous liver. There was, however, a negative correlation between serum ferritin and alpha-foetoprotein concentrations. Ferritin was purified from PLC tissue obtained from three patients at necropsy and the distribution of isoferritins was determined by isoelectric focusing. Acidic isoferritins similar to those previously found in PLC tissue were obtained. Their acidic nature was confirmed chromatographically using DEAE cellulose. Because the serum ferritin in patients with PLC probably consists of a mixture of normal and acidic isoferritins, it is likely that the serum assay used in the present study underestimated the actual concentrations present. With the development of an assay which utlises a specific antibody against acidic PLC isoferritins, serum ferritin may prove to be a second marker for PLC.
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PMID:Serum and tumour ferritins in primary liver cancer. 7 42

When normal lymphocytes were stimulated with PHA in the presence of serum taken from patients with various liver diseases, lower lymphocyte transformation was seen in many cases. The occurrence of a serum inhibitory factor in liver diseases tends to increase with the progress of the disease from acute hepatitis to cirrhosis of the liver. No such inhibitory factor was detected in two asymptomatic HBs-antigen carriers. When the inhibitory factor was fractionated by DE-52 column chromatography, an active component was obtained and shown to have mobilities from alpha2-globulin to beta-globulin in cellulose acetate membrane electrophoresis. However, two active fractions were separated by DEAE-cellulose column chromatography with stepwise increases of the concentration of the acetate buffer and their mobilities were consistent with those of alpha1-globulin and alpha2-globulin, respectively. In 11 cases of acute hepatitis which were followed for at least 6 months, three out of four inhibitory factor positive cases developed into the chronic form and the other became a protracted case. On the other hand, six out of seven inhibitory factor negative cases completely recovered and the remaining case followed a protracted course.
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PMID:Studies on an inhibitory factor to phytohemagglutinin-induced lymphocyte transformation found in the serum of patients with various liver diseases. 8 90

Immunologically pure human transferrin type C (TfC) was isolated from the plasmas of 11 individual healthy donors. After conversion into the 2Fe-form, the preparations were analysed by polyacrylamide gel electrophoresis and chromatography on DEAE-cellulose. In all samples studied by either method the presence of three components, designated A, B and C, was observed. Calculations from eight chromatograms yielded the following relative proportions for the components: A:6%, B:62% and C:32%. The quantity of iron bound played no role in this chromatographic resolution. The components were immunologically identical but their sialic acid content increased inthe order of A less than B less than C. The presence of galactose as an ultimate residue of the oligosaccharide chains in TfC component A was confirmed by a biological test. This observation together with the results of earlier analyses for hexose, hexosamine and galactose in the subfractions from Behringwerke human transferrin, suggests that sialic acid is probably the only variable among TfC components A, B and C. Loss of sialic acid from component C during the isolation of TfC was excluded as an explanation for the presence of the other two components. The electrophoretic appearance of TfC samples from five patients with liver disease (chronic active hepatitis, cirrhosis or alcoholic liver) did not noticeably differ from that of TfC FROM HEALTHY PERSONS. Baboon transferrin resembles TfC with respect to sialic acid heterogeneity. This species was therefore studied to decide whether sialic acid is gradually lost from transferrin in the circulation or whether transferrin is not fully sialylated before discharge from the hepatocyte. Using DEAE-cellulose chromatography no difference was found between baboon transferrin molecules which were less than 6h old and those which had a mean age of 8.9 days. By inference it is suggested that the reason for the multiplicity of TfC is also likely to be biosynthetic.
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PMID:The molecular components of human transferrin type C. 40 68

The newly discovered circulating growth hormone binding proteins dictate a re-evaluation of the state of GH in plasma in health and disease as the binding proteins are known to affect GH metabolism and action. We describe a rapid and simple GH-binding assay that allows determination of free and complexed plasma GH, as well as GH-binding protein activity as an index of GH-binding protein levels, with relative ease. The method is based on incubation of plasma with 125I-GH and separation of bound from free GH on small DEAE-cellulose columns; it can be used on a large scale for routine determinations. The results obtained by this method are comparable to those obtained with the previously used slow and more cumbersome gel filtration technique. Initial data obtained in normal subjects and certain disease states show that the bound fraction of plasma GH is similar in men, women and children, is unaffected by pregnancy or acute infection, but is marginally decreased in liver cirrhosis. In acromegaly, binding protein activity also appears normal when allowance is made for partial saturation of the binding proteins by the high prevailing GH levels. The technique we describe should facilitate investigations of normal and abnormal regulation of the GH binding proteins.
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PMID:A rapid and simple assay for growth hormone-binding protein activity in human plasma. 320 82

Sera from 9 persons with either biopsy-proven alcoholic liver disease or a history of chronic, excessive ethanol consumption were analyzed for their content of various hydrolases. Compared to controls, significant elevations in the following enzyme activities were seen in sera from the patient population: acid phosphatase (2.0-fold), beta-glucuronidase (2.1-fold), hexosaminidase (1.4-fold), and alpha-L-fucosidase (2.3-fold). In addition, alpha-mannosidase activity, previously reported to be unchanged in cases of hepatic cirrhosis [Reglero et al., Clinica chim. Acta 130: 155-158], (1980) was found to be significantly increased (p less than 0.001) when assays were performed at acid (pH 4.5) or intermediate (pH 5.5) hydrogen ion concentrations. Fractionation of sera on DEAE-Sephadex columns showed that the increase in alpha-mannosidase activity in the serum of patients with alcoholic liver disease was due to increases in the level of at least one 'acid alpha-mannosidase' and two intermediate pH optimum alpha-mannosidases. The general increase in the activity of a group of glycosidases is consistent with a hypothesis involving decreased clearance of glycoproteins from the blood of persons with hepatic cirrhosis.
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PMID:Serum alpha-mannosidase in patients with alcoholic liver disease. 671 94

Homogenates of liver from cases of hepatic cirrhosis due to alpha 1-antitrypsin deficiency (PiZZ) alcoholism were analyzed for their content of various lysosomal enzymes. Also determined were the specific activities of lactate dehydrogenase, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, and creatine phosphokinase in the extracts of liver from cases of both kinds of hepatic cirrhosis: all of these activities were within the range of control values. Similarly, the specific activities of the following lysosomal hydrolases were unremarkable: acid phosphatase, beta-mannosidase, beta-fucosidase, beta-glucuronidase and beta-glucosidase. Hexosaminidase specific activity was increased twofold in livers from the cases of cirrhosis due to alpha 1-antitrypsin deficiency. The specific activity of alpha-mannosidase (measured at pH 4.5) in homogenates of livers from PiZZ individuals with cirrhosis and those with alcoholic cirrhosis was increased two- to four-fold. Chromatography of the high-speed supernatant fraction from homogenates of livers of cirrhotic and noncirrhotic individuals on columns of DEAE-cellulose resolved alpha-mannosidase activity into two components: under the conditions employed, acid pH optimum (pH 4.5) alpha-mannosidase did not bind to the resin, whereas intermediate pH optimum (pH 5.5) alpha-mannosidase could be eluted with 0.1 mol/l NaCl. Liver from one case of (PiZZ) alpha 1-antitrypsin deficiency and emphysema, without demonstrable cirrhosis, was found to contain normal levels of both acid alpha-mannosidase and intermediate alpha-mannosidase. However, cases of cirrhosis due to alpha 1-antitrypsin deficiency contained twice as much acid alpha-mannosidase and only one third to one fourth as much intermediate alpha-mannosidase as controls. The deficiency in hepatic intermediate alpha-mannosidase was also observed in 5 of 5 cases of alcoholic cirrhosis.
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PMID:Altered alpha-mannosidase isoenzymes in the liver in hepatic cirrhosis. 697 51

A circulating anticoagulant was isolated from the plasma of a 42-year-old man with cirrhosis and hepatocellular carcinoma who had an unusual coagulation test profile. The patient developed a fatal coagulopathy, unresponsive to protamine therapy or plasma exchange following liver biopsy. However, at presentation, routine hemostasis assays were normal. The patient had mucocutaneous bleeding but the sole laboratory abnormality was a prolonged thrombin time (TT = 99 s, normal 25-35 s). Protamine titration indicated activity equivalent to a heparin concentration of 6-7 U/ml. Antithrombin III (AT III) antigen and activity were markedly elevated. The anticoagulant activity, purified from plasma by DEAE chromatography, was identified as a glycosaminoglycan (GAG). GAG anti-thrombin activity was completely abolished by heparin lyase III. Based on the degree of sulfation and HPLC pattern, the GAG was classified as heparan sulfate. Low levels (4 microM) of purified GAG markedly prolonged the TT (>120 s) but not the activated partial thromboplastin time (PTT) (31.4 s). In a Factor Xa assay, the GAG exhibited a potency equivalent to 0.06 U of low molecular weight heparin per nmol of uronic acid. Patients with endogenous circulating glycosaminoglycans can present with unusual laboratory coagulation test profiles. These reflect complex dysfunction of hemostasis, leading to difficulty in providing diagnosis and effective care.
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PMID:Structural characterization and functional effects of a circulating heparan sulfate in a patient with hepatocellular carcinoma. 969 91

The reasons for the decreased functional activity of prothrombin in liver diseases are still speculative. When a highly purified preparation of prothrombin from a patient with liver cirrhosis is available, the cause of prothrombin abnormalities may be researched on a molecular basis. In this study, prothrombin (6.7 mg) was purified from the ascites fluid (1130 mL) of a patient with liver cirrhosis by barium citrate adsorption, ammonium sulfate elution, DEAE Sephacel and Heparin Sepharose CL-6B column chromatography steps. The molecular weight of this prothrombin was the same as that of normal prothrombin purified from a normal plasma pool. The specific activities were found to be 3.36 U/mg in the one stage clotting assay and 28.9 U/mg in the staphylocoagulase/chromogenic substrate assay, while the normal prothrombin specific activities were 3.92 U/mg and 30.1 U/mg respectively. When N-terminal amino acid sequence analysis was carried out, it was seen that the first 20 residues were identical to the normal human prothrombin excepting the Gla at position #14.
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PMID:Determination of the N-terminal amino acid sequence of the purified prothrombin from a patient with liver cirrhosis. 1094 94

Transferrin (T f) and its carbohydrate-deficient isoform (CDT) were measured by radioimmunoassay in phosphate-buffered saline extracts of two informative areas of cerebral cortex tissue obtained at autopsy from alcoholics without other associated disease (n = 4); alcoholics with cirrhosis of the liver (n = 4) and agematched controls (n = 4). Total T f was also measured in two informative cortical areas from five dementia cases. All cases were male. Total immunoreactive T f was assayed directly in the extract, CDT immunoreactivity in the concentrated eluate after the sialylated form was removed by passing through DEAE-Sephacel at pH 5.65. Brain CDT averaged 10% of total T f overall. Although replicate extractions of individual samples gave consistent assays for both substances, there was wide variation both between different cortical areas from a given case and between cases within groups. There were no significant differences between total T f levels in uncomplicated alcoholics, dementia cases and controls, but cirrhotic alcoholics gave significantly higher values. The CDT: T f ratio was not increased in the brains of either group of alcoholics compared to controls. Whereas the serum CDT: T f ratio is an excellent marker of recent alcohol consumption, brain T f and CDT concentrations do not mark alcoholism nor dementia, and their biological variability diminishes their usefulness as disease indices. However, brain T f may be a marker of cirrhosis-induced changes.
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PMID:Concentrations of transferrin and carbohydrate-deficient transferrin in postmortem human brain from alcoholics. 2673 90