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)

We evaluated the utility of SDS-PAGE/Western blot and CE coupled with MS (CE-MS) for detection of urinary polypeptide biomarkers of renal disease in patients with IgA-associated glomerulonephritides. In a reference cohort of 402 patients with various renal disorders and 207 healthy controls, we defined CE-MS patterns of renal damage and IgA nephropathy (IgAN). In a blinded analysis of a separate cohort of patients with IgAN (n = 10), Henoch-Schoenlein purpura (HSP) with nephritis (n = 10), and IgA-associated glomerulonephritis due to hepatitis C virus (HCV)-induced cirrhosis (n = 9), and healthy controls (n = 12), we compared SDS-PAGE/Western blot and CE-MS against clinical urinalysis for detection of urinary proteins/polypeptides. Urinalysis indicated proteinuria for 50, 90, and 33% of patients, respectively, and for none of the healthy controls. SDS-PAGE/Western blot showed urinary polypeptides abnormality for 90, 80, and 67% of patients, respectively, and for none of the healthy controls. CE-MS indicated a Renal Damage Pattern in 80, 80, and 100 of patients, respectively, and in 17% of healthy controls, with the more specific IgAN Pattern in 90, 90, and 1%, respectively, and in none of the healthy controls. Based on differences in CE-MS patterns, the disease mechanisms may differ among various IgA-associated glomerulonephritides. These exploratory findings should be evaluated in a prospective study with contemporaneous renal biopsy and urinary testing. If validated, it may be feasible to adapt the CE-MS methodology to develop novel tests to detect renal injury at earlier stages, assess clinical manifestations, and monitor responses to therapy in patients with IgA-associated renal diseases.
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PMID:Electrophoretic methods for analysis of urinary polypeptides in IgA-associated renal diseases. 1800 14

Familial hypobetalipoproteinemia (FHBL) is an autosomal codominantly inherited disorder of lipoprotein metabolism characterized by decreased concentrations of low-density lipoprotein-cholesterol and of apolipoprotein B (apoB). Mutations of APOB gene lead to the formation of truncated forms of apoB. The study aimed at determining the truncated form of apoB responsible for FHBL associated with liver cirrhosis in a 27-year-old man. Analysis of the patient's lipoproteins has been performed by SDS-PAGE electrophoresis followed by immunoblotting with monoclonal antibodies. DNA of the family (proband, daughter, wife, father, and mother) was extracted, and PCR amplification was realized; amplicons were screened and sequenced. Electrophoresis allowed us to identify a truncated form of apoB (close to apoB 59%), associated with a new heterozygous apoB variant, 8402 C>G. This mutation creates a stop codon (TAC>TAG, Y2807X) and predicts to generate a truncated protein (apoB-61.9%). No other causes of cirrhosis were established by comprehensive clinical and biological investigations. We described here an unusual clinical observation of a patient with FHBL and early development of liver cirrhosis due to a new truncated form of apoB.
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PMID:Cryptogenic cirrhosis in a patient with familial hypocholesterolemia due to a new truncated form of apolipoprotein B. 1906 Jun 34

Despite many shortcomings, liver biopsy is regarded as the gold standard for assessing liver fibrosis. A less invasive and equally or more reliable approach would constitute a major advancement in the field. Proteomics can aid discovery of novel serological markers and these proteins can be measured in patient blood. A major challenge of discovering biomarkers in serum is the presence of highly abundant serum proteins, which restricts the levels of total protein loaded onto gels and limits the detection of low abundance features. To overcome this problem, we used two-dimensional gel electrophoresis (2-DE) over a narrow pH 3-5.6 range since this lies outside the range of highly abundant albumin, transferrin and immunoglobulins. In addition, we used in-solution isoelectric focusing followed by SDS-PAGE to find biomarkers in hepatitis C induced liver cirrhosis. Using the pH 3-5.6 range for 2-DE, we achieved improved representation of low abundance features and enhanced separation. We found in-solution isoelectric focusing to be beneficial for analyzing basic, high molecular weight proteins. Using this method, the beta chains of both complement C3 and C4 were found to decrease in serum from hepatitis C patients with cirrhosis, a change not observed previously by 2-DE. We present two proteomics approaches that can aid in the discovery of clinical biomarkers in various diseases and discuss how these approaches have helped to identify 23 novel biomarkers for hepatic fibrosis.
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PMID:New approaches for biomarker discovery: the search for liver fibrosis markers in hepatitis C patients. 2141 Feb 21

HRQoL is impaired in cirrhosis. Establishing the relevance of depression, anxiety, alexithymia and cirrhosis stage on the patients' HRQoL. Sixty cirrhotics underwent a neuropsychological assessment, including ZUNG-SDS, STAI Y1-Y2 and TAS-20. Minimal hepatic encephalopathy (MHE) was detected by PHES, HRQoL by Short-Form-36 (SF-36). Depression was detected in 34 patients (57 %, 95%CI = 44-70 %), state-anxiety in 16 (27 %, 95%CI = 15-38 %), trait-anxiety in 17 (28 %, 95%CI = 17-40 %), alexithymia in 14 (31 % 95%CI = 16-46 %) and MHE in 22 (37 %, 95%CI = 24-49 %). Neuropsychological symptoms were unrelated to cirrhosis stage, hepatocellular carcinoma or MHE. A significant correlation was observed among psychological test scores and summary components of SF-36. At multiple linear regression analysis including Child-Pugh and MELD scores, previous-HE and the psychological test scores as possible covariates, alexithymia and depression as well as to the Child-Pugh score were significantly related to the SF-36 mental component; while trait-anxiety was the only variable significantly and independently related to the SF-36 physical component. Depression, state and trait-anxiety and alexithymia symptoms are frequent in cirrhotics and are among the major determinants of the altered HRQoL.
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PMID:Depression, anxiety and alexithymia symptoms are major determinants of health related quality of life (HRQoL) in cirrhotic patients. 2329 69

Liver fibrosis results from extracellular matrix accumulation during the wound healing process when the liver is insulted with chronic viral infection, inflammation, or alcoholic diseases. The current diagnosis of liver fibrosis is mainly dependent on biopsy, which is an invasive approach. Identification of serological biomarkers has been considered as the most promising way for early detection of the disease. Although several biomarkers in liver fibrosis have been identified, the problem is that these markers can be also detected in fibrogenesis that occurred in other organs. In this study, we have identified and characterized some cellular proteins that can be recognized by autoantibodies in the sera from patients with precirrhotic stage of liver fibrosis. Among 180 sera from patients with liver fibrosis, 14.4% (26/180) of sera contained autoantibody against a protein migrating around 47 kDa on SDS-PAGE gel. Indirect immunofluorescence assay using purified autoantibody against the 47-kDa protein showed that this protein mainly localized in the cytoplasm. Using immunoproteomic approach, the 47-kDa protein was identified as alpha-enolase. In further study, the frequency of antialpha-enolase antibody in sera from patients with precirrhotic stage of liver fibrosis (21.6%, 27/125) was significantly higher than that in sera from patients with cirrhosis (9.1%, 5/55) and liver cancer (14.3%, 12/84), as well as in sera from healthy individuals (4.1%, 3/74). Therefore, alpha-enolase is an autoantigen that elicits autoimmune response in liver fibrosis and can be a potential prognostic factor for liver fibrosis diagnosis.
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PMID:Using immunoproteomics to identify alpha-enolase as an autoantigen in liver fibrosis. 2345 88

To identify novel tumor-associated proteins, we analyzed the protein expression patterns from experimental hepatocellular carcinoma (HCC) that were induced using hepatocarcinogenesis models in rats. Rats were subjected to two previously described protocols of hepatocarcinogenesis using diethylnitrosamine as a carcinogen: the alternative Solt-Farber (aS&F) protocol, which induces HCC within 9 months, and Schiffer's model, which induces cirrhosis and multifocal HCC within 18 weeks. The patterns of protein expression from tumors and normal liver tissue were examined by SDS-PAGE and the bands identified at 33-34 kDa were analyzed by mass spectrometry. The prostaglandin reductase 1 (PTGR1) showed the highest number of peptides, with a confidence of level >99%. The increased expression of PTGR1 in tumors was confirmed in these two models by Western blotting and by increase in alkenal/one oxidoreductase activity (25-fold higher than normal liver). In addition, the gene expression level of Ptgr1, as measured by qRT-PCR, was increased during cancer development in a time-dependent manner (200-fold higher than normal liver). Furthermore, PTGR1 was detected in the cytoplasm of neoplastic cells in rat tumors and in 12 human HCC cases by immunohistochemistry. These analyses were performed by comparing the expression of PTGR1 to that of two well-known markers of hepatocarcinoma, Glutathione S-transferase pi 1 (GSTP1) in rats and glypican-3 in humans. The increased expression and activity of PTGR1 in liver carcinogenesis encourage further research aimed at understanding the metabolic role of PTGR1 in HCC and its potential application for human cancer diagnosis and treatment.
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PMID:Increased expression of prostaglandin reductase 1 in hepatocellular carcinomas from clinical cases and experimental tumors in rats. 2485 74

Human alpha-1 antitrypsin (AAT) is an abundant serum protein present at a concentration of 1.0-1.5 g L(-1). AAT deficiency is a genetic disease that manifests with emphysema and liver cirrhosis due to the accumulation of a misfolded AAT mutant in hepatocytes. Lung AAT amount is inversely correlated with chronic obstructive pulmonary disease (COPD), a serious and often deadly condition, with increasing frequency in the aging population. Exposure to cigarette smoke and products of fossil fuel combustion aggravates AAT deficiency and COPD according to mechanisms that are not fully understood. Taking into account that these fumes contain particles that can release nickel to human airways and skin, we decided to investigate interactions of AAT with Ni(ii) ions within the paradigm of Ni(ii)-dependent peptide bond hydrolysis. We studied AAT protein derived from human blood using HPLC, SDS-PAGE, and mass spectrometry. These studies were aided by spectroscopic experiments on model peptides. As a result, we identified three hydrolysis sites in AAT. Two of them are present in the N-terminal part of the molecule next to each other (before Thr-13 and Ser-14 residues) and effectively form one N-terminal cleavage site. The single C-terminal cleavage site is located before Ser-285. The N-terminal hydrolysis was more efficient than the C-terminal one, but both abolished the ability of AAT to inhibit trypsin in an additive manner. Nickel ions bound to hydrolysis products demonstrated an ability to generate ROS. These results implicate Ni(ii) exposure as a contributing factor in AAT-related pathologies.
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PMID:Ni(ii) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency. 2557 32

Objective Growth hormone (GH) deficiency has recently been reported as a cause of nonalcoholic fatty liver disease (NAFLD), and GH supplementation has been shown to improve the histology of NAFLD. The aim of the present study was to clarify the relationship between the histological severity of NAFLD and production of the GH/insulin-like growth factor 1 (IGF-1) axis. Methods A total of 222 Japanese patients with liver biopsy-confirmed NAFLD and 55 patients with hepatitis C virus (HCV)-related chronic liver disease (CLD) were enrolled in the present study. The serum levels of GH, IGF-1, and IGF-binding protein 3 (IGFBP-3) were measured and their relationships with the histological severity of liver disease were assessed. To exclude age- and sex-related differences, the IGF-1 standard deviation score (IGF-1:SDS) was determined for each patient. Results With respect to the stage of fibrosis in patients with NAFLD, the serum GH levels were higher and the serum IGFBP-3 levels and IGF-1:SDSs were lower in patients with cirrhosis (grade F4 fibrosis) than in patients grade F1-F3 fibrosis; moreover, these differences were statistically significant (all p<0.01). The GH, IGF-1, and IGFBP-3 levels were not correlated with fibrosis in patients with HCV-related CLD. Furthermore, the GH levels were lower and the IGFBP-3 levels were significantly higher in patients with severe steatosis (S3) than in patients with mild to moderate steatosis (S1-S2) (p<0.05). Conclusion Increased GH levels and decreased IGF-1 and IGFBP-3 levels might contribute to the progression of NAFLD. The GH/IGF-1 axis may be important in the development of NAFLD, but not in patients with HCV-related CLD.
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PMID:The Relationship between the Growth Hormone/Insulin-like Growth Factor System and the Histological Features of Nonalcoholic Fatty Liver Disease. 2825 Feb 90

Inherited bone marrow failure syndromes (IBMFS) are caused by mutations in genes involved in genomic stability. Although they may be recognized by the association of typical clinical features, variable penetrance and expressivity are common, and clinical diagnosis is often challenging. DNAJC21, which is involved in ribosome biogenesis, was recently linked to bone marrow failure. However, the specific phenotype and natural history remain to be defined. We correlate molecular data, phenotype, and clinical history of 5 unreported affected children and all individuals reported in the literature. All patients present features consistent with IBMFS: bone marrow failure, growth retardation, failure to thrive, developmental delay, recurrent infections, and skin, teeth or hair abnormalities. Additional features present in some individuals include retinal abnormalities, pancreatic insufficiency, liver cirrhosis, skeletal abnormalities, congenital hip dysplasia, joint hypermobility, and cryptorchidism. We suggest that DNAJC21-related diseases constitute a distinct IBMFS, with features overlapping Shwachman-Diamond syndrome and Dyskeratosis congenita, and additional characteristics that are specific to DNAJC21 mutations. The full phenotypic spectrum, natural history, and optimal management will require more reports. Considering the aplastic anemia, the possible increased risk for leukemia, and the multisystemic features, we provide a checklist for clinical evaluation at diagnosis and regular follow-up.
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PMID:Refining the phenotype associated with biallelic DNAJC21 mutations. 2970 Aug 10


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