Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Less than a decade ago, the use of continuous mammalian cell lines for the production of cloned proteins was considered strictly a research tool. At that time, few thought it possible to allay the many safety concerns associated with transformed cells. It soon became clear that mammalian expression systems had numerous advantages over bacteria for production of therapeutic proteins, initiating a multidisciplinary effort to address these concerns in a thorough and reliable manner. The success of these efforts is exemplified by the emergence of product molecules into the market. Today, there are seven recombinant human therapeutics that have received FDA approval. Almost half of them (OKT3, t-PA, and EPO) are produced in mammalian cells, with the remainder produced in bacteria (insulin, growth hormone, and alpha-interferon) or yeast (hepatitis vaccine). At least a dozen more recombinant cell culture products are in advanced human clinical trials. With the accumulation of data and experience, continuous mammalian cell lines will no doubt be the preferred hosts for many future products of biotechnology.
 ...
PMID:Downstream processing of proteins from mammalian cells. 136 66

16 coagulant and 7 fibrinolytic parameters were determined in 121 normal subjects and 456 patients with various types of viral hepatitis. The results showed that plasma concentration of F VIII: c, vWF: Ag and vWF: Ag/VIII: c (P less than 0.01) were much higher than those in the controls. Plasma level of other coagulant factors was progressively reduced when the severity of hepatitis was decreased. The changes of fibrinolytic activity suggest that t-PA, PL and FDP were increased, while PAI, PLG, and alpha-PI were decreased. The results of this study may provide an experimental basis for further study of hemorrhage mechanism and prognosis in patients with viral hepatitis.
 ...
PMID:[Changes in plasma coagulant factors and plasma fibrinolytic activity in patients with viral hepatitis]. 166 71

The respective roles of intravascular coagulation (DIC) and fibrinolysis were assessed in severe chronic liver disease by measuring thrombin-antithrombin (TAT) complexes, tissue-type plasminogen activator antigen (tPA Ag) and fibrinogen and fibrin degradation products (FgDP and FbDP respectively) in 66 patients with liver disease caused by cirrhosis (n = 34) or chronic hepatitis (n = 32) as compared to findings in a control group (n = 30). There was a significant increase of TAT complexes (P less than 0.01), tPA Ag (P less than 0.002), FDP and FbDP (P less than 0.001) in patients as compared to controls. FbDP increase was more evident in patients with cirrhosis than in those with hepatitis (P less than 0.01). Significant correlations between these parameters with some liver function tests were also demonstrated. Thus, in patients with severe liver disease, an increased thrombin activity, as demonstrated by high TAT levels; followed by hyperfibrinolysis suggest that a low grade DIC may occur.
 ...
PMID:Thrombin activation and increased fibrinolysis in patients with chronic liver disease. 190 1

The introduction of factor VIII and IX concentrates in the early 1960s brought a significant change in the hemophiliac's life. In consequence hemophilia treatment has been improving rapidly since, and today most life-threatening hemorrhages are controlled by replacement therapy. Hemophilic arthropathy through recurrent joint and muscle bleedings occurs later in life and is often limited to one joint only. Major surgery in hemophiliacs involves little more risk than in non-hemophilic patients, provided of course there is close teamwork between surgeon and hematologist. The most frequent causes of death are no longer hemorrhages but blood-product-associated AIDS and hepatic failure. Fortunately these side effects have been overcome by the use of virus-inactivated concentrates which in Switzerland have been generally administered since 1986. Factor VIII and IX concentrates must contain a precisely declared quantity of factor VIII and IX activity respectively, with a high specific activity. High-purity concentrates should be preferred because of the hazardous effect of foreign proteins administered intravenously in large quantities over a long period. Activation of fibrinolysis with consequent failure of hemostasis or even worsening of hemorrhage may be a clinically relevant side-effect of DDAVP therapy. When DDAVP is used for prophylactic treatment before surgery, an interval of one hour between the intravenous administration of DDAVP and surgery ensures the latter is performed at the time of highest factor VIII and von Willebrand factor level but with already decreased t-PA and fibrinolytic activity. If DDAVP is used in case of hemorrhage or postoperatively, however, the whole fibrinolytic potential must be taken into account. In these cases subcutaneous administration is advantageous due to more protracted t-PA release and the subsequent lower fibrinolytic activity, which can more easily be neutralized by tranexamic acid. To prevent hemophilic arthropathy, correct replacement therapy in hemarthroses is essential: it should be performed as early as possible, preferably in a home therapy program; adequate levels of factor VIII or IX should be achieved and maintained over a sufficient length of time. Hemophiliacs who did not receive replacement therapy during childhood often need major surgery because of severely destructed joints. Joint replacement by total knee and hip prostheses has proved very successful if certain special conditions are fulfilled. Surgical indications should, however, be carefully considered and the possibilities and limits of replacement therapy should be well known. Blood-product-associated hepatitis will be of prognostic relevance in many hemophiliacs treated formerly with non-virus-inactivated concentrates.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Current clinical aspects in hemophilia treatment]. 250 19

After infection with 10(3) plaque-forming units of mouse hepatitis virus strain 3 (MHV-3) in vivo, peripheral blood mononuclear cells and splenic cells expressed procoagulant activity (PCA) in a pattern directly correlating with susceptibility to disease. Mononuclear cells from BALB/cJ mice, a strain which is fully susceptible to MHV-3, expressed a greater than 500-fold increase in PCA. PCA was first detected within 12 hr of infection; prior to histologic evidence of disease and viral replication, it reached maximal levels 48 hr post-infection (p.i.) and persisted until the death of the animals 5 to 7 days p.i. Mononuclear cells from C3HeB/FeJ mice expressed a significant but lesser titer of PCA, with elevated PCA persisting throughout the chronically infected state until death of the animals 4 to 6 mo p.i. Basal levels of PCA were detected in mononuclear cells from fully resistant A/J mice despite the presence of large amounts of virus in livers, spleens, and sera from these animals. When mononuclear cells expressing high PCA were subfractionated, monocytes were found to be the cellular source of greater than 96% of the PCA activity. Increased plasminogen activator activity was found in monocytes from resistant A/J mice at the time when PCA was markedly elevated in BALB/cJ and C3HeB/FeJ mice. This activity persisted for 5 to 7 days p.i., but was undetectable 10 days p.i. at a time when the mice had cleared the virus from their blood streams. These observations suggest that monocyte PCA may be important in the pathogenesis of MHV-3 disease, whereas the production of monocyte plasminogen activators may contribute to resistance of A/J mice to MHV-3-induced liver disease.
 ...
PMID:The immune response to mouse hepatitis virus: expression of monocyte procoagulant activity and plasminogen activator during infection in vivo. 299 39

Activated macrophages (m phi) exhibited cytotoxic effects on isolated liver cells and produced plasminogen activator (PA) in vitro. A high molecular weight fraction of normal human serum (Fr-1) was shown to reduce the m phi-mediated hepatocytotoxicity and enhance the PA activity of activated m phi. Conversely, a lower molecular weight fraction of serum (Fr-3) was found to enhance the hepatotoxic potential and decrease the PA activity of activated m phi. Although similar effects were seen with serum fraction prepared from patients with acute hepatitis, somewhat different influences were observed with serum components from patients with chronic active hepatitis or liver cirrhosis: Fr-1 from patients with chronic active hepatitis was less active in reducing m phi-mediated hepatocytotoxicity, and and Fr-3 was more active in enhancing it, in comparison with fractions from individuals or patients with active hepatitis. Fr-3 from patients with liver cirrhosis was shown to be remarkably less active in enhancing m phi-mediated hepatocytotoxicity. Furthermore, Fr-1 from patients with liver cirrhosis reduced PA activity, Fr-3 was less active in decreasing such activity. These findings suggest that the serum components may regulate m phi-mediated hepatocytotoxicity as well as PA secretion of activated m phi. Our studies also suggested the possibility that relative doses of these serum components may differ in various pathological conditions of the liver.
 ...
PMID:Modulation of the macrophage hepatocytotoxicity and plasminogen activator activity of activated macrophages from guinea pigs by serum components from normal human and patients with liver diseases. 668 38

These studies describe an assay of whole blood clot lysis as measured by release of 125I-fibrinogen degradation products. Optimal rates of lysis were obtained at 37 degrees C in 10-12 mM EDTA or 3,8% citrate and 4 u of thrombin/ml. Eighteen normal subjects and eight patients (six with recurrent deep vein thrombosis, one with thrombasthenia, and one with hepatitis and resolving portal vein thrombosis) were studied using this assay. The clots of seventeen of the eighteen normal subjects were 50% lysed at 40 hours. The clots of the patients with venous thrombosis and thrombasthenia did not lyse whereas the clots of the patient with hepatitis, resolving portal vein thrombosis and a high plasminogen activator level (0.32 CTA units) were 100% lysed at 4.5 hrs.
 ...
PMID:Observations on optimal conditions for lysis of whole blood clots and use of this assay as a screening assay in clinical investigation. 682 Jan 94

We studied the tissue plasminogen activator (t-PA) levels in the plasma of patients with acute hepatitis (AH), severe acute hepatitis (AHs) and fulminant hepatitis (FH). Plasma t-PA levels were measured consecutively on the first, third and seventh days of hospitalization. Plasma t-PA levels were markedly higher in AHs and FH than in AH (p < 0.05, p < 0.01, respectively) on the first day, but did not differ significantly between AHs and FH on this day. The t-PA levels decreased markedly on the third and seventh days in AHs (both p < 0.05), but did not change from the first day to the third and seventh days in FH. The t-PA levels on the third and seventh days were higher in FH than in AHs (both p < 0.05). There was a significant increase in the plasma t-PA level before an episode of encephalopathy in FH compared with levels in AHs. These observations suggest that t-PA level may be useful as a prognostic parameter in patients with acute hepatic injury.
 ...
PMID:[The clinical significance of plasma tissue plasminogen activator (t-PA) levels in severe acute or fulminant hepatitis]. 955 77

Cyclooxgenase (COX) and phospholipase A(2) (PLA(2)) are crucial rate-limiting enzymes involved in the conversion of arachidonic acid to prostaglandin H(2), the precursor of various compounds including prostaglandins (PGs), prostacyclin, and thromboxanes in the process of PGs' synthesis. Recent studies have shown increased levels of COX(2) in adjacent cirrhotic tissue of hepatocellular carcinoma. The relationship between the expression of COX(2) or cytosolicPLA(2) (cPLA(2)) and liver fibrosis has not been described previously. We used 45 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsies from patients with chronic hepatitis, consisting of 7 cases of F(0), 10 cases of F(1), 10 cases of F(2), 9 cases of F(3) and 9 cases of liver cirrhosis (LC) according to the New Inuyama Classification of the staging of liver fibrosis. The expression of COX(2) and cPLA(2) was investigated by immunohistochemistry, western blotting and image analysis. The positive signals for COX(2) and cPLA(2) were observed in the cytoplasm of hepatocytes. The signal intensity of COX(2) increased significantly with the progression of liver fibrosis (P<0.001) and no significant difference was observed in the relative amount of cPLA(2) from group F(0) to group LC. According to the New Inuyama Classification of hepatitis activity grading, 45 samples were classified as group A(1) (23 cases), group A(2) (19 cases) and group A(3) (3 cases). No significant differences were found in the relative amount of COX(2) and cPLA(2) between group A(1) and group A(2-3). Significant correlation was observed between the relative amount of COX(2) and hyaluronan (P<0.01). Our findings suggested that COX(2) may be involved in liver fibrogenesis.
 ...
PMID:Expression of cyclooxygenase 2 and cytosolic phospholipase A(2) in the liver tissue of patients with chronic hepatitis and liver cirrhosis. 1207 14

The pathogenesis of nonalcoholic steatohepatitis (NASH) is unclear, despite epidemiological data implicating FFAs. We studied the pathogenesis of NASH using lipoapoptosis models. Palmitic acid (PA) induced classical apoptosis of hepatocytes. PA-induced lipoapoptosis was inhibited by acyl-CoA synthetase inhibitor but not by ceramide synthesis inhibitors, suggesting that conversion products other than ceramide are involved. Phospholipase A(2) (PLA(2)) inhibitors blocked PA-induced hepatocyte death, suggesting an important role for PLA(2) and its product lysophosphatidylcholine (LPC). Small interfering RNA for Ca(2+)-independent phospholipase A(2) (iPLA(2)) inhibited the lipoapoptosis of hepatocytes. PA increased LPC content, which was reversed by iPLA(2) inhibitors. Pertussis toxin or dominant-negative Galpha(i) mutant inhibited hepatocyte death by PA or LPC acting through G-protein-coupled receptor (GPCR)/Galpha(i). PA decreased cardiolipin content and induced mitochondrial potential loss and cytochrome c translocation. Oleic acid inhibited PA-induced hepatocyte death by diverting PA to triglyceride and decreasing LPC content, suggesting that FFAs lead to steatosis or lipoapoptosis according to the abundance of saturated/unsaturated FFAs. LPC administration induced hepatitis in vivo. LPC content was increased in the liver specimens from NASH patients. These results demonstrate that LPC is a death effector in the lipoapoptosis of hepatocytes and suggest potential therapeutic values of PLA(2) inhibitors or GPCR/Galpha(i) inhibitors in NASH.
 ...
PMID:Lysophosphatidylcholine as a death effector in the lipoapoptosis of hepatocytes. 1795 Dec 22


1 2 Next >>