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Biomedical subjects

T Y Hsu

Publications and source records attributed to T Y Hsu.

76 records · Page 5Linked to original sources

Integration of hepatitis virus DNA near c-myc in woodchuck hepatocellular carcinoma.

A total of 33 hepatocellular carcinomas, induced in woodchucks by chronic infection with woodchuck hepatitis virus (WHV), a virus closely related to the human hepatitis B virus, were analyzed for the state of viral DNA, the expression of viral genes and of different cellular proto-oncogenes. Low levels of viral replication and presence of integrated viral forms including sequences of the enhancer element, appeared as a general rule in these tumors. Enhanced expression of one or more of the nuclear protooncogenes: c-myc, N-myc, c-fos, c-jun and jun-B was frequently observed. In two hepatomas, elevated expression and allelic alterations of c-myc were subsequent to integration of WHV DNA near the c-myc coding domain. The viral strategy for insertional activation of c-myc in these tumors appeared basically identical to that of mammalian retroviruses in T-cell lymphomas of mice and rats. Whether insertional mutagenesis of different oncogenes may be more generally linked to liver oncogenesis induced by WHV and hepatitis B viruses remains to be determined.

Animals↗

Molecular characterization of a cDNA clone encoding the Epstein-Barr virus (EBV) DNase.

RNA from IdUrd-treated P3HR1 cells was used for the construction of a cDNA library and screened with B95-8 EBV DNA BamHI fragment B and G probes. One clone, BG9, containing a 1.7 kb cDNA insert was further studied. Complete DNA sequence analysis revealed that BG9 encompassed the B95-8 EBV DNA sequences from nucleotide 120,747 to nucleotide 122,412 and corresponded to the BGLF5 open reading frame of the EBV DNase gene. Comparison of the sequences of BG9 with that of published B95-8 EBV DNA indicated that there were 14 different bases which results in 7 amino acid residue changes. The product of in vitro transcription/translation of a subclone, pGEM-BG9, contained the EBV DNase activity and a 52 kDa protein was immunoprecipitated from the in vitro translation products using serum from a patient with nasopharyngeal carcinoma which contained a high level of anti-DNase activity. Northern hybridization of P3HR1 RNA with the BG9 probe revealed a complex pattern of transcription in this region. Subgenomic DNA fragments were then used to map these RNA species to the B95-8 EBV DNA sequence. The result of S1 nuclease analysis indicated that a DNase ORF containing transcript sized 2.0 kb is initiated at nucleotide 122,435 +/- 1 and terminated at nucleotide 120,741 of the EBV genome.

Amino Acid Sequence↗

Corynebacterium pseudotuberculosis exotoxin: fatal hemolytic anemia induced in gnotobiotic neonatal small ruminants by parenteral administration of preparations containing exotoxin.

Inoculation of live Corynebacterium pseudotuberculosis, culture supernatant, ammonium sulfate-fractionated crude exotoxin, or chromatographically purified exotoxin preparations into gnotobiotic small ruminants (n = 13) caused death of the ruminants within 48 hours. Characteristic changes observed in animals living greater than or equal to 2 hours after inoculation included hemorrhage and edema at the site of injection, severe hemolytic anemia and hemoglobinuria, dark red fluid in body cavities, lung edema, and icterus. The crude exotoxin preparation caused a syndrome of acute shock in 2 lambs that died within 15 minutes after inoculation. Clinical and pathologic responses of animals inoculated with culture supernatant and purified toxin were similar. Histopathologic evidence indicated that the exotoxin caused necrotic changes in the proximal convoluted tubules of the kidneys. Inoculation with live organisms caused multiple foci of suppurative inflammation in skeletal muscle and adjacent adipose tissue, whereas such changes were not observed in animals administered exotoxin preparations. Although C pseudotuberculosis exotoxin induced a hemolytic anemia in the experimental animals, it did not lead to in vitro lysis of ovine, caprine, or bovine erythrocytes, unless they had been sensitized with Rhodococcus (Corynebacterium) equi filtrate. The toxic sphingomyelin-specific phospholipase D from C pseudotuberculosis had a molecular weight of 31,000 daltons and an isoelectric point of approximately 9.6. The elution profile of exotoxin on a carboxymethyl Sephadex column was studied and the majority of the enzymatic activity was eluted by a NaCl gradient (0.25M to 0.7M) with a maximum at 0.35M NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hemolytic↗