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)

Capillary zone electrophoresis (CZE) offers the potential for automating serum protein electrophoretic analysis traditionally performed on standard thin-layer agarose gels. The following describes the use of CZE compared to agarose gel electrophoresis (AGE) for the detection of dysproteinemia and paraproteinemia in a clinical study involving 240 patients. The study includes within-run and between-run reproducibility data on the Paragon CZE 2000 Clinical Capillary Electrophoresis System, in addition to concordance data between the two methodologies. Paraprotein quantitation studies comparing AGE versus CZE were also performed. Reproducibility for the automated CZE system was superior to the AGE system. Improved reproducibility for the CZE method is largely due to measuring protein absorbance directly at 214 nm versus the traditional AGE method that measures the amount of dye adsorbed to protein. Reproducibility data as percent coefficient of variance (% CV) for the five classic bands in a normal control serum for between-run precision ranged from 1.2 to 4.5% for CZE compared to AGE, which ranged from 3.8 to 8.0% CV. Concordance studies between AGE and CZE involving dysproteinemias including hypogammaglobulinemia, polyclonal and monoclonal gammopathies, acute and chronic inflammation, nephrosis, hepatodegenerative disease, cirrhosis, and iron deficiency anemia showed 96% agreement. Paraprotein classification, which compared the CZE immunosubtraction method to immunofixation electrophoresis (IFE) on agarose, showed 100% agreement. Certain dysproteinemias involving beta lipoprotein were in partial concordance due to the inability of the CZE procedure to detect this component. Detection limits for monoclonal gammopathies, providing they were not comigrating with other proteins, were IgG 50 mg/dL, IgM 75 mg/dL, and IgA 75 mg/dL. Paraprotein quantitative studies between the two methods showed less than a +/- 0.2 g/dL variation.
 ...
PMID:Comparison of serum protein electrophoresis by agarose gel and capillary zone electrophoresis in a clinical setting. 937 70

Monitoring of posttransplantation lymphoproliferative disorder (LPD) is usually based on imaging, which lacks sensitivity. A prospective study in 911 consecutive recipients of liver transplants was conducted to assess the value of gammopathy monitoring by serum protein electrophoresis (SPE) and to compare it with conventional follow-up methods. Patients systematically underwent SPE testing just before transplantation, at least twice during the first year after transplantation, and once a year thereafter. Patients with LPD underwent SPE testing every month. Immunofixation was done if abnormalities were detected by SPE. Gammopathy was observed in 114 patients, 18 of whom had onset of LPD. In 3 other patients, LPD developed, but no gammopathy was detected before onset of LPD or while LPD was present. Multivariate analyses showed gammopathy (relative risk [RR], 65.3), more than one transplantation (RR, 7.5), and viral cirrhosis (RR, 2.8) to be independent prognostic factors associated with occurrence of LPD. LPD was treated by reducing immunosuppression, with or without chemotherapy, administration of anti-CD20 monoclonal antibody, or surgery. The mortality rate was 24% (5 of 21 patients). Remission, which occurred in 13 patients, was associated with disappearance of gammopathy in 10 patients. In 5 patients, normalization of SPE results preceded the diagnosis of remission based on imaging, by a mean of 4 months. For diagnosis of LPD remission, the positive and negative predictive values of disappearance of gammopathy were 91% and 100%, respectively; and gammopathy monitoring was more sensitive than imaging (100% and 38%, respectively). Gammopathy monitoring is an inexpensive, noninvasive, sensitive way to detect LPD and assess the efficacy of treatment. It could be used routinely in follow-up of recipients of transplants.
 ...
PMID:Detection of gammopathy by serum protein electrophoresis for predicting and managing therapy of lymphoproliferative disorder in 911 recipients of liver transplants. 1152 Jul 79

Five groups of 30 male Japanese quail, each 7-w-old, were fed diets containing 0, 1, 3, 5, or 10% (w/w) of dehulled H dolosum seed. Half of the birds from the each group were killed at 6 and 24 w after beginning of the trial. At the end of 6th w, neither mortality nor clinical sign occurred in test groups. In the 5 and 10% inclusion levels, mild to moderate hepatic injury was detected as evidenced by mild karyomegaly, moderate fatty change, focal or portal fibrosis, bile duct hyperplasie, and ovalocyte proliferation along with lower serum protein and albumin levels. By the termination of the experiment (24 w), 5 birds died in the 10% dosed group. Hepatic cirrhosis was the most prominent finding in the 5 and 10% group; at these levels, serum protein and albumin values decreased significanty while billuribin and ALP levels increased. Based on relative weights and histological evaluations, testicularatrophywasdosedependent. These results partly affirm earlier studies that the quail is highly resistant to the toxic effects of H dolosumseed. However, the resistance to H dolosum is less than Senecio Jacobae and Crotalaria spectabilis when considering tissue injury.
 ...
PMID:Toxicity of dietary Heliotropium dolosum seed to Japanese quail. 1236 Nov 6

Capillaria hepatica is an extremely common parasite of rats. Several human cases have also been reported from various parts of the world and recently these aroused the clinical interests. The present study was undertaken to investigate the biological observations of C. hepatica and the changes occurring in blood picture and serum protein in the experimentally infected hosts. The source of C. hepatica obtained from the deposit of non-embryonated eggs encapsulated in the liver of house rats(Rattus norvegicus) in Seoul. The eggs isolated from the infected liver tissues by the freshly prepared artificial gastric juice at 37 C and embryonated in the incubator 27 degrees to 30 degrees C for four to five weeks. For the observation of migratory pathway to the liver, ten mice were infected orally with 1,000 embryonated eggs of C. hepatica, and another ten mice were infected intraperitoneally. No larvae were found in the washings of peritoneal cavity after oral infection, but after the third day of infection, the larvae were isolated from liver tissues. These indicated that the majority of larvae are transported to the liver by the hepatic portal system. On the other hand, 1,000 embryonated eggs of C. hepatica were inoculated into the peritoneal cavity of mice by mantoux syringe containing antibiotics. One third of inoculated eggs hatched out in the peritoneum during two days after inoculation, hatched in the peritoneal cavity invade directly to the surface of liver. Twenty white rats were infected orally with 1,000 to 2,000 embryonated eggs for the study of the development of C. hepatica in the liver and histopathological changes of the infected liver in the course of infection. C. hepatica in the liver of white rats developed rather slowly at the first tenth day after infection, but at the 13th day developed rapidly in its size. The worms were sexually differentiated at the l7th day after infection. At the 20th fully formed eggs appeared in the white or yellowish lesions on the surface of rat liver and they are also found in uterine tubule of the female worm. After the 33rd day, male worm disappeared and only female worms packed with eggs were detected in the liver tissues. However the long hair-like tightly coiled worms were also usually found in the hepatic cysts, and the degenerated or dead worms were observed in the small cysts on the surface of the liver at the 59 th day after infection. Microscopical examination on the first week after infection revealed inflammatory reactions with the dilatation of central vein, Kupffer cell mobilization, focal necrosis and perivascular infiltration. After two weeks of infection granulomatous inflammation were observed around or adjacent to the worms in the lobules. The worms are surrounded by macrophages, multinucleated giant cells, a dense infiltration of lymphocytes, monocytes, neutrophils and, especially, eosinophils. After the third and fourth week, the microscopical findings of infected rat livers have shown proliferation of connective tissues and regeneration of liver cells. During the fifth to sixth week after infection, rat liver showed marked proliferation of fibrous connective tissues encapsulated the worms and massive deposition of the eggs. At the later time the liver reveals many pseudolobules which are caused by postnecrotic cirrhosis. These are irregularly subdivided into lobule by a fibrous septum. The worms were fragmented by the phagocytes and encapsulated by connective tissues. And then finally they appeared to be replaced by the calcium-like material. The liver shows typical cirrhosis after the eighth week after infection. In order to investigate the changes of blood picture and serum protein components of rabbits infected with C. hepatica, twenty rabbits were divided into four groups by the doses of eggs. Group A was given doses of 1,000 embryonated eggs, group B 5,000 eggs, group C 10,000 eggs and group D 30,000 eggs. The pictures of blood especially leukocyte and eosinophil counts and of serum protein were checked every week for ten weeks in the course of infections. The marked elevation of the leukcocyte, eosinophil counts and percentage of eosinophils was observed at the sixth to the seventh week in the course of infection in all groups of rabbits. At the tenth week after infection a decrease was shown in their counts. However in the heavily infected groups (Group C & D) these values persisted relatively in high levels even thereafter. In the white rats given doses of 1,000 to 2,000 eggs, eosinophil counts increased to the peak at the fourth week and decreased at the seventh week after infection. The changes in serum protein components of infected rabbits were investigated by paper electrophoresis. Blood collections were done by the cardiac puncture in the early morning. Serum total protein was determined by Biurets method, serum protein fractionating and A/G ratio by paper electrophoresis using Whatman No.l filter paper and barbital buffer (pH 8.6, ionic strength 0.06). Total protein increased at the sixth and seventh week after infection and the albumin and A/G ratio had decreased significantly in the heavily infected groups at the fifth and sixth week. The alpha-globulin and beta-globulin were not significant in the lightly infected groups(Group A & B), but they decreased after seventh week in the heavily infected groups. The gamma-globulin and &ggr;/A ratio of the heavily infected groups were significantly increased at fifth to seventh week. Statistically the calculation of entropy was applied to the data obtained in all groups. In the lightly infected groups, the entropy was included almost in the normal ranges, however in the heavily infected groups it was excluded from the normal range during the first to eighth week after infection.
 ...
PMID:[The experimental studies on Capillaria hepatica] 1291 11

We applied our 'clinical glycomics' technology, based on DNA sequencer/fragment analyzers, to generate profiles of serum protein N-glycans of liver disease patients. This technology yielded a biomarker that distinguished compensated cirrhotic from noncirrhotic chronic liver disease patients, with 79% sensitivity and 86% specificity (100% sensitivity and specificity for decompensated cirrhosis). In combination with the clinical chemistry-based Fibrotest biomarker, compensated cirrhosis was detected with 100% specificity and 75% sensitivity. The current 'gold standard' for liver cirrhosis detection is an invasive, costly, often painful liver biopsy. Consequently, the highly specific set of biomarkers presented could obviate biopsy in many cirrhosis patients. This biomarker combination could eventually be used in follow-up examinations of chronic liver disease patients, to yield a warning that cirrhosis has developed and that the risk of complications (such as hepatocellular carcinoma) has increased considerably. Our clinical glycomics technique can easily be implemented in existing molecular diagnostics laboratories.
 ...
PMID:Noninvasive diagnosis of liver cirrhosis using DNA sequencer-based total serum protein glycomics. 1515 12

Liver cirrhosis is a worldwide health problem. Reliable, noninvasive methods for early detection of liver cirrhosis are not available. Using a three-step approach, we classified sera from rats with liver cirrhosis following different treatment insults. The approach consisted of: (i) protein profiling using surface-enhanced laser desorption/ionization (SELDI) technology; (ii) selection of a statistically significant serum biomarker set using machine learning algorithms; and (iii) identification of selected serum biomarkers by peptide sequencing. We generated serum protein profiles from three groups of rats: (i) normal (n=8), (ii) thioacetamide-induced liver cirrhosis (n=22), and (iii) bile duct ligation-induced liver fibrosis (n=5) using a weak cation exchanger surface. Profiling data were further analyzed by a recursive support vector machine algorithm to select a panel of statistically significant biomarkers for class prediction. Sensitivity and specificity of classification using the selected protein marker set were higher than 92%. A consistently down-regulated 3495 Da protein in cirrhosis samples was one of the selected significant biomarkers. This 3495 Da protein was purified on-chip and trypsin digested. Further structural characterization of this biomarkers candidate was done by using cross-platform matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) peptide mass fingerprinting (PMF) and matrix-assisted laser desorption/ionization time of flight/time of flight (MALDI-TOF/TOF) tandem mass spectrometry (MS/MS). Combined data from PMF and MS/MS spectra of two tryptic peptides suggested that this 3495 Da protein shared homology to a histidine-rich glycoprotein. These results demonstrated a novel approach to discovery of new biomarkers for early detection of liver cirrhosis and classification of liver diseases.
 ...
PMID:Molecular classification of liver cirrhosis in a rat model by proteomics and bioinformatics. 1537 89

Proteomic profiling of serum is an emerging technique to identify new biomarkers indicative of disease severity and progression. The objective of our study was to assess the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify multiple serum protein biomarkers for detection of liver disease progression to hepatocellular carcinoma (HCC). A cohort of 170 serum samples obtained from subjects in the United States with no liver disease (n = 39), liver diseases not associated with cirrhosis (n = 36), cirrhosis (n = 38), or HCC (n = 57) were applied to metal affinity protein chips for protein profiling by SELDI-TOF MS. Across the four test groups, 38 differentially expressed proteins were used to generate multiple decision classification trees to distinguish the known disease states. Analysis of a subset of samples with only hepatitis C virus (HCV)-related disease was emphasized. The serum protein profiles of control patients were readily distinguished from each HCV-associated disease state. Two-way comparisons of chronic hepatitis C, HCV cirrhosis, or HCV-HCC versus healthy had a sensitivity/specificity range of 74% to 95%. For distinguishing chronic HCV from HCV-HCC, a sensitivity of 61% and a specificity of 76% were obtained. However, when the values of known serum markers alpha fetoprotein, des-gamma carboxyprothrombin, and GP73 were combined with the SELDI peak values, the sensitivity and specifity improved to 75% and 92%, respectively. In conclusion, SELDI-TOF MS serum profiling is able to distinguish HCC from liver disease before cirrhosis as well as cirrhosis, especially in patients with HCV infection compared with other etiologies.
 ...
PMID:SELDI-TOF MS profiling of serum for detection of the progression of chronic hepatitis C to hepatocellular carcinoma. 1572 46

Primary metabolic disorders are a disparate group of diseases that may or may not be accompanied by hepatic manifestations. Those with liver involvement may show a range of histopathologic changes. Proper histologic diagnosis requires correlation with clinical and laboratory data, including evaluation for mutations either via serum protein electrophoresis or through formal genetic analysis. This article is a review of the three most common inherited metabolic disorders which may present with a hepatitic pattern. In alpha1-antitrypsin disorder, there is a broad range of clinical presentations, age at presentation, and histological features ranging from "neonatal hepatitis" to a chronic progressive hepatitis in later childhood and adulthood. Hence, this disorder must be in the differential diagnosis of liver disease of the very young, and in older children and adults, with or without coexistent overt pulmonary symptoms. In Wilson disease, presentation tends to be in older childhood or the adult, with a progressive chronic hepatitis. Cystic fibrosis may feature a characteristic obstructive biliary syndrome, coexisting with the many extrahepatic manifestations of this debilitating disease. Lastly, the progressive familial intrahepatic cholestasis (PFIC) syndromes are given as examples of inherited metabolic conditions in which relentlessly progressive cholestatic liver disease eventuates over years in end-stage cholestatic liver disease with cirrhosis. Distinguishing features include absence of elevated serum gamma-glutamyl transpeptidase (GGT) in PFIC-1 and PFIC-2, and elevated GGT in PFIC-3. However, molecular studies are required for a confident diagnosis of the rare PFIC syndromes.
 ...
PMID:Hepatitic inherited metabolic disorders. 1735 91

The GlycoFibroTest and GlycoCirrhoTest are noninvasive alternatives for liver biopsy that can be used as a follow-up tool for fibrosis patients and to diagnose cirrhotic patients, respectively. These tests are based on the altered N-glycosylation of total serum protein. Our aim was to investigate the impact of etiology on the alteration of N-glycosylation and whether other characteristics of liver patients could have an influence on N-glycosylation. In human liver patients, no specific alteration could be found to make a distinction according to etiological factor, although alcoholic patients had a significant higher mean value for the GlycoCirrhoTest. Undergalactosylation did not show a significantly different quantitative alteration in the cirrhotic and noncirrhotic population of all etiologies. Importantly, patients with an elevation of total bilirubin level (>2 mg/dl) had a strong increase of glycans modified with alpha1-6 fucose. The fucosylation index was therefore significantly higher in fibrosis/cirrhosis and hepatocellular carcinoma patients with elevated total bilirubin levels irrespective of etiology. Furthermore, in a multiple linear regression analysis, only markers for cholestasis significantly correlated with the fucosylation index. In mouse models of chronic liver disease, the fucosylation index was uniquely significantly increased in mice that were induced with a common bile duct ligation. Mice that were chronically injected with CCl(4) did not show this increase. Apart from this difference, common changes characteristic to fibrosis development in mice were observed. Finally, mice induced with a partial portal vein ligation did not show biological relevant changes indicating that portal hypertension does not contribute to the alteration of N-glycosylation.
 ...
PMID:Impact of elevation of total bilirubin level and etiology of the liver disease on serum N-glycosylation patterns in mice and humans. 2005 95

Wilson's disease (WD) is characterized by excessive accumulation of intracellular copper in liver and extrahepatic tissues, leading to significant oxidative stress and tissue damage. To date, several diagnostic biomarkers for WD such as serum ceruloplasmin, serum or urine copper levels and copper content in liver have been identified. However, these biomarkers may not be convincing for the diagnosis in some WD patients. To identify additional novel diagnostic biomarkers, we compared the serum protein profiles of asymptomatic childhood WD patients (n=20), without neurologic manifestation or liver cirrhosis, with normal controls (n=13). Fourteen spots, five up-regulated and nine down-regulated (>2-fold), were differentially expressed in WD patients in comparison to normal control on 2-DE. Among them, three spots were down-regulated in both male and female WD. MS/MS analysis revealed that the three spots were complement component C3, complement factor B and alpha-2 macroglobulin. By comparative proteome analysis, complement component C3, complement factor B and alpha-2 macroglobulin, which are related to oxidative stress and inflammation, turned out to be good candidates for novel diagnostic biomarkers for early stages of WD.
 ...
PMID:Proteomic analysis of sera of asymptomatic, early-stage patients with Wilson's disease. 2055 97


<< Previous 1 2 3 4 5 6 Next >>