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

In the course of 4 years, among 11,738 admissions there were 245 (2.08%) patients with cholestasis (106 women and 139 men). Intrahepatic cholestasis (i.c.) was detected in 46.5%, and extrahepatic (e.c.) in 53.5%. The most frequent cause of i.c. were alcoholic and nonalcoholic chr. liver disease (fatty liver, chr. hepatitis, cirrhosis) (37% and 30%), acute viral hepatitis (15%) and toxic liver injury (14%) respectively. The causes of e.c. were: choledocholithiasis (44%), cancer of the pancreatic head (15%), cancer of gallbladder and extrahepatic ducts (12%) and cancer of liver (10%). The causes of c. were benigne, in 78.2%, while malignant neoplasms were present in 21.8%. Out of the multitude of laboratory tests two appeared particularly significant: glut, transpeptidase was pathologic in 81% of alcoholic liver disease, in 62% of the cases with obstructive jaundice and in 27.7% of malignant neoplasms. LX-lipoprotein examined in 52 patients was positive in 24% of i.c., and 60% of e.c. Proliferation of bile ducts was the most frequent finding in surgical liver biopsies in choledocholithiasis cases.
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PMID:Differential diagnosis, laboratory tests and histology in 245 patients with cholestasis. 52 15

Hepatic insufficiency is generally caused by active liver cirrhosis with portal hypertension. The final stage is the exogenous hepatic coma. Much rarer is the endogenous hepatic coma caused by fulminant acute hepatitis or severe intoxications. In the treatment of hepatic insufficiency it is first necessary to eliminate all exacerbating factors such as too high protein-intake, gastrointestinal bleedings, abuse of alcohol and diuretics. Because hepatic encephalopathy is mainly produced by toxic intestinal protein metabolites no protein should be adminstered at the beginining of the disease. The production of toxic protein metabolites in the gut can be diminished as well by enemas with sodium acetate buffer (pH 4, 5) as by neomycin (6-8 gm daily). Because long-term treatment with neomycin reduces also the physiological intestinal bacteria combination with lactulose (70-100 gm daily) is better. Treatment with lactulose reduces not only significantly hyperammoniemia but also increases serum phenols. The same effect have so-called ammonia reducing amino acids such as arginine, ornithine and glutamic acid. In endogenous hepatic coma blood exchange transfusions, liver perfusions and charcoal perfusions are necessary. Nevertheless, the prognosis of hepatic insufficiency caused by fulminant hepatitis is very poor in the final stage of the disease. Therefore early diagnosis and treatment in special departments with intensive care is necessary.
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PMID:[Therapy of hepatic insufficiency]. 91 52

In order to clone hepatitis C (blood-borne non-A, non-B hepatitis) virus, lambda gt11-cDNA library was constructed from RNA extracted from 100 liters serum collected from 1,047 donors with elevated ALT levels and negative for hepatitis B virus-DNA. The library was immunoscreened on Y1090 cells with pooled serum obtained from patients with acute hepatitis C or chronic hepatitis C. By screening 29 clones specific for Japanese hepatitis C infection were isolated. The specificity of these clones for hepatitis C infection was determined by panels constructed in 3 laboratories. Of these, 12 clones were specific for American hepatitis C infection as well. The nucleotide sequence (201 bp) of one of them was determined to be unique compared to known human viruses including hepatitis A virus, hepatitis B virus and hepatitis D virus. Southern blot analysis showed the absence of the sequence of the human genome in the clone. The predicted amino acid sequence is rich in residues of lysine, arginine, glutamic acid and asparagine, while lacking leucine, cysteine and methionine.
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PMID:Cloning of a cDNA associated with acute and chronic hepatitis C infection generated from patients serum RNA. 250 78

Significant elevation of glutamic acid and glutamine concentrations in CSF was observed in hepatic encephalopathic patients with fulminant hepatitis and liver cirrhosis. However, the ratios of CSF glutamic acid to CSF glutamine levels and of CSF to serum glutamic acid and glutamine levels were significantly higher only in cirrhotic patients with hepatic encephalopathy. CSF glutamine levels were positively correlated with blood ammonia and CSF tyrosine levels in cirrhotic patients. The results indicate that CSF glutamic acid and glutamine levels are important tools in diagnosing hepatic encephalopathy in severe liver disease.
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PMID:Glutamic acid and glutamine levels in serum and cerebrospinal fluid in hepatic encephalopathy. 615 Jul 6

A 10 year old boy, in grade IV hepatic coma, was treated by combination of XAD-4 resin hemoperfusion (HP), activated charcoal HP (Adsorba 300C, Gambro), exchange transfusion by up to 12.0 liters of fresh whole blood, and regular dialysis. Serum free amino acids' values were consecutively assessed during 4 days of treatment. The liver was 490 gr in weight at autopsy and histologic examination revealed cellular necrosis compatible with fulminant hepatitis. Pre-treatment values of alanine, lysine, proline, phenylalanine, arginine, threonine, tyrosine and methionine were increased by 2 to 38 times of normal control, while those of cystine, glutamic acid, serine and glycine were minimally increased up to 1.7 times. Histidine, isoleucine, leucine and valine, on the other hand, were decreased by 20 to 30% and aspartic acid was the lowest at 14% of normal control. The effect of XAD-4 resin HP and exchange transfusion was rather non-specific by decreasing the total amount of amino acids. The molar ratios of branched chain amino acids vs. aromatic amino acids or essential amino were elevated by activated charcoal HP, but, did not reach to normal range.
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PMID:[Variation of serum free amino acids in fulminant hepatitis treated with hepatic assists (author's transl)]. 740 29

The coronavirus, mouse hepatitis virus strain A59 (MHV), expresses a chymotrypsin-like cysteine proteinase (3CLpro) within the gene 1 polyprotein. The MHV 3CLpro is similar to the picornavirus 3C proteinases in the relative location of confirmed catalytic histidine and cysteine residues and in the predicted use of Q/(S, A, G) dipeptide cleavage sites. However, less is known concerning the participation of aspartic acid or glutamic acid residues in catalysis by the coronavirus 3C-like proteinases or of the precise coding sequence of 3CLpro within the gene 1 polyprotein. In this study, aspartic acid residues in MHV 3CLpro were mutated and the mutant proteinases were tested for activity in an in vitro trans cleavage assay. MHV 3CLpro was not inactivated by substitutions at Asp3386 (D53) or Asp3398 (D65), demonstrating that they were not catalytic residues. MHV 3CLpro was able to cleave at a glutamine-glycine (QG3607-8) dipeptide within the 3CLpro domain upstream from the predicted carboxy-terminal QS3636-6 cleavage site of 3CLpro. The predicted full-length 3CLpro (S3334 to Q3635) had an apparent mass of 27 kDa, identical to the p27 3CLpro in cells, whereas the truncated proteinase (S3334 to Q3607) had an apparent mass of 24 kDa. This 28-amino-acid carboxy-terminal truncation of 3CLpro rendered it inactive in a trans cleavage assay. Thus, MHV 3CLpro was able to cleave at a site within the putative full-length proteinase, but the entire predicted 3CLpro domain was required for activity. These studies suggest that the coronavirus 3CL-proteinases may have a substantially different structure and catalytic mechanism that other 3C-like proteinases.
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PMID:Determinants of mouse hepatitis virus 3C-like proteinase activity. 914 89

A novel copper-binding protein was identified in the liver supernatant (100,000 x g) of Indian childhood cirrhosis (ICC), purified to apparent homogeneity and characterized [corrected]. Purified major copper-binding protein (MCuBP) is solely responsible for binding about 35% of the total supernatant copper. Elution profile of ICC liver supernatant on Sephadex G-75 column chromatography showed three peaks. About 60% of the total supernatant copper was resolved in peak II, whereas zinc content was insignificant in this peak. But peak II was almost missing in a gel elution profile of control liver supernatant. The control group included cases of various liver diseases viz. neonatal hepatitis, septicemia, and mixed nodular cirrhosis. Copper-binding proteins of peak II further purified on ion-exchange chromatography and elution profile showed that peak II was a MCuBP with high copper-binding capacity (10 g atoms/mol of native protein). SDS-PAGE of this protein also revealed the existence of a single band with molecular mass of about 50 kD. UV spectra of MCuBP showed the maximal absorbance at 254 nm. Unlike the classical metallothionein, the amino acid composition of MCuBP revealed the presence of aromatic amino acids and higher content of glutamic acid and aspartic acid followed by glycine and serine. The ratio (0.3) of basic amino acids to acidic amino acids strongly indicates that it is an acidic protein. The cysteine content in this protein was insignificant, which further corroborates the possibility that the acidic amino acids might be prominent candidates for binding copper. Thus, the 50-kD MCuBP apparently makes a major contribution to the total copper-binding activity in ICC liver cytosol and may play a significant role in hepatic intracellular copper accumulation.
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PMID:Identification of a novel copper-binding protein from the liver of Indian childhood cirrhosis: purification and physicochemical characterization [corrected]. 980 48

Although fibrin glue has been widely used as a surgical adhesive, its components, fibrinogen and thrombin, obtained from human blood are not completely free from the risk of virus infection due to acquired immune deficiency and hepatitis. Recently, we have reported that a polymer pair composed of gelatin and poly(L-glutamic acid) (PLGA) promptly forms a gel and can firmly bond to soft tissues when crosslinked with the aid of water-soluble carbodiimide (WSC). The present study was undertaken to design a new PLGA-gelatin glue without using WSC. Two kinds of PLGA with molecular weights of 71 and 22 kDa were employed to prepare N-hydroxysuccinimide (NHS) activated derivatives. The NHS-activated PLGA could be synthesized at high yields and was found to be stable for an extended time without losing the ability to crosslink with gelatin when stored under a dry-cold condition. This NHS-activated PLGA could spontaneously form a gel with gelatin in an aqueous solution within a short time, comparable to a commercial fibrin glue, when gelation was allowed to proceed at pH 8.3. The NHS-activated PLGA prepared from PLGA with the molecular weight of 22 kDa could be readily dissolved at high concentrations and its ability to form a gel was maintained for more than 10 min when an acidic 8% NHS-activated PLGA solution was used. The bonding strength of PLGA gelatin glues with natural tissue was higher than that of fibrin glue. These findings strongly suggest that this combination of gelatin and NHS-PLGA is very promising as a surgical adhesive and may possibly replace fibrin glues prepared from human blood components.
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PMID:A novel surgical glue composed of gelatin and N-hydroxysuccinimide activated poly(L-glutamic acid): Part 1. Synthesis of activated poly(L-glutamic acid) and its gelation with gelatin. 985 88

A polymeric prodrug of prostaglandin E(1) (PGE(1)) was synthesized using galactosylated poly(L-glutamic acid hydrazide) (Gal-HZ-PLGA) as a biodegradable and targetable carrier to hepatocytes. Poly(L-glutamic acid hydrazide) was prepared by reacting poly(gamma-benzyl-L-glutamate) with hydrazine monohydrate, followed by reaction with 2-imino-2-methoxyethyl-1-thiogalactosides to obtain Gal-HZ-PLGA after i.v. injection. (111)In-labeled galactosylated poly(L-glutamic acid hydrazide) ((111)In-Gal-HZ-PLGA) rapidly accumulated in the liver in a dose-dependent manner, whereas (111)In-poly(L-glutamic acid hydrazide) did not, indicating the involvement of a galactose-specific mechanism in the uptake of (111)In-Gal-HZ-PLGA. Fractionation of liver cells revealed that (111)In-Gal-HZ-PLGA was preferentially taken up by liver parenchymal cells. After being taken up by the liver, (111)In-Gal-HZ-PLGA was gradually degraded, and radioactive metabolites with low molecular weight were detected within 10 min after injection. Then, PGE(1) or [(3)H]PGE(1) was coupled to Gal-HZ-PLGA via a hydrazone bond under mild conditions to obtain PGE(1) conjugate. After i.v. injection, [(3)H]PGE(1) conjugate was rapidly taken up by the liver (more than 80% of the dose). After injection of the conjugate, (3)H radioactivity remained in the liver, representing about 70% of the dose, even at 24 h, whereas little radioactivity remained in the organ at 1 h after the injection of free [(3)H]PGE(1). Finally, its pharmacological activity was examined in mice with fulminant hepatitis induced by peritoneal injection of carbon tetrachloride. The i.v. injection of PGE(1) conjugate at a dose of 1 mg (0.074 mg PGE(1))/kg effectively inhibited the increase of plasma glutamic pyruvic transaminase activity, whereas twice this dose (0.15 mg/kg) of free PGE(1) had little effect. These results suggest that the PGE(1) conjugate is an excellent polymeric prodrug of PGE(1) for hepatitis therapy.
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PMID:Development of a hepatocyte-specific prostaglandin E(1) polymeric prodrug and its potential for preventing carbon tetrachloride-induced fulminant hepatitis in mice. 1045

Based on the relationship between in vivo disposition of macromolecules and their physicochemical and biological characteristics obtained through clearance concept-based pharmacokinetic analysis, polymeric prodrugs of prostaglandin E(1)(PGE(1)) were designed stepwise and evaluated on their targeting and therapeutic efficiencies. First poly-L-lysine (PLL) and poly-L-glutamic acid (PLGA) with an ethylenediamine (ED) spacer were modified with 2-imino-2-methoxyethyl 1-thiogalactoside to obtain galactosylated derivatives. After intravenous injection in mice, Gal-ED-PLGA was selectively taken up by the liver parenchymal cells via receptor-mediated endocytosis, while Gal-PLL accumulated in the liver as well as PLL mostly due to electrostatic interaction. Although Gal-ED-PLGA showed good targeting efficacy, its PGE(1) conjugate synthesized with activated PGE(1) by carbonyldiimidazole method failed to show therapeutic effects probably due to inactivation of PGE(1) during conjugation and lack of release in the tissue. In order to overcome these problems, we next conjugated PGE(1) to galactosylated poly-(L-glutamic acid) hydrazide (Gal-HZ-PLGA) in which PGE(1) was easily coupled to Gal-HZ-PLGA via a hydrazone bond in weak acidic solution (pH 5) at room temperature. The PGE(1)-Gal-HZ-PLGA conjugate labeled with [(111)In] or [(3)H]PGE(1) rapidly accumulated in the liver parenchymal cells. In addition, the PGE(1) conjugate effectively inhibited the increase of the GPT level in plasma, while free PGE(1) indicated no therapeutic efficacy even at more than ten times higher doses, in carbon tetrachloride-induced hepatitis mice. These findings suggest potentials of polymeric targeting systems of PGE(1) to hepatocyte utilizing galactose recognition.
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PMID:Design of polymeric prodrugs of prostaglandin E(1) having galactose residue for hepatocyte targeting. 1051 58


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