[Arterioportal fistula as a cause of esophageal varices bleeding].
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Arteriovenous Fistula↗
Biomedical subjects
M I Meyer
Publications and source records attributed to M I Meyer.
[Ticlopidine-induced cholestasis].
UNLABELLED: We report a case of ticlopidine-induced cholestatic hepatitis. CASE SUMMARY: An 82-year-old man suffered a myocardial infarction in February 1998. Because of persistent angina pectoris a coronary stent was implanted in May 1998. At this time medication with 1 x 250 mg ticlopidine was started in addition to the preexistent medication of aspirin 1 x 100 per day, metoprolol fumarate 1 x 95 mg per day and isosorbide dinitrate 1 x 100 mg per day. Three weeks after starting ticlopidine the patient complained of itching, and on day 28 painless jaundice developed. At this time, the serum activities of alkaline phosphatase (923 U/l), gamma-GT (823 U/l) and total bilirubin concentration (129 mumol/l) were markedly elevated, whereas the activities of the transaminases (AST 131 U/l, ALT 194 U/l) were slightly increased. An extra- or intrahepatic biliary obstruction was ruled out, and there were no signs of a toxic, infectious or immunological cause for the hepatic injury. Liver biopsy showed centro-acinar cholestasis. After drug discontinuation the itching stopped after 4 weeks and jaundice disappeared after 2 weeks. Eight months after the onset of symptoms, the activities of alkaline phosphatase (226 U/l) and gamma-GT (213 U/l) were still elevated but the patient was asymptomatic. CONCLUSIONS: Ticlopidine-induced mild serum liver enzyme elevations have been observed in some studies (incidence 1-2%). The incidence of severe hepatitis has been estimated at 0.0013%. Only a few cases (in approximately 20 patients receiving ticlopidine) of a severe cholestatic pattern of injury have been reported. In all cases the jaundice resolved and serum liver enzyme concentrations normalised over a period of months. Characteristically, liver biopsies demonstrated centro-acinar cholestasis. Monitoring of serum liver enzyme concentrations is not recommended. When itching or jaundice occur in a patient taking ticlopidine, the possibility of toxic liver damage should be taken into account.
Aged↗
The use of antibodies to the polypyrimidine tract binding protein (PTB) to analyze the protein components that assemble on alternatively spliced pre-mRNAs that use distant branch points.
We are using the rat beta-tropomyosin (beta-TM) gene as a model system to study the mechanism of alternative splicing. Previous studies demonstrated that the use of the muscle-specific exon is associated with the use of distant branch points located 147-153 nt upstream of the 3' splice site. In addition, at least one protein, the polypyrimidine tract binding protein (PTB), specifically interacts with critical cis-acting sequences upstream of exon 7 that are involved in blocking the use of this alternative exon in nonmuscle cells. In order to further study the role of PTB, monoclonal antibodies to PTB were prepared. Anti-PTB antibodies did not inhibit the binding of PTB to RNA because they were able to supershift RNA-PTB complexes. To determine if additional proteins interact with sequences within the pre-mRNA, 35S-met-labeled nuclear extracts from HeLa cells were mixed with RNAs and the RNA-protein complexes were recovered by immunoprecipitation using antibodies to PTB. When RNAs containing intron 6 were added to an 35S-met-labeled nuclear extract, precipitation with PTB antibodies showed a novel set of proteins. By contrast, addition of RNAs containing introns 5 or 7 gave the same results as no RNA, indicating that these RNAs are unable to form stable complexes with PTB. These results are in agreement with our previous studies demonstrating that PTB interacts with sequences within intron 6, but not with sequences within introns 5 and 7. When 35S-met-labeled HeLa nuclear extracts were mixed with biotinylated RNA containing intron 6 and the RNA-protein complexes were recovered using streptavidin-agarose beads, an identical pattern of proteins was observed when compared with the immunoprecipitation assay. Analysis of the proteins that assembled on introns 5, 6, or 7 using biotinylated RNA revealed a unique set of proteins that interact with each of these sequences. The composition of proteins interacting with sequences associated with the use of the 3' splice site of intron 6 included proteins of 30, 40, 55, 60, 65, 70, 80, and 100 kDa. Microsequencing identified two of the proteins to be Sam68 and the Far Upstream Element Binding Protein (FBP) from the c-myc gene. In addition, a comparison of the proteins that assemble on introns from the alpha- and beta-TM genes that utilize distant branch points revealed common as well as unique proteins that assemble on these introns. These studies identify a set of proteins, in addition to PTB, that are likely involved in the use of distant branch sites associated with the use of alternatively spliced introns.
Alternative Splicing↗