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J Prelich

Publications and source records attributed to J Prelich.

4 recordsLinked to original sources
PubMed1999

A fresh look at augmenter of liver regeneration in rats.

Augmenter of liver regeneration (ALR) is a hepatotrophic protein originally identified by bioassay in regenerating rat and canine livers following partial hepatectomy and in the hyperplastic livers of weanling rats, but not in resting adult livers. The ALR gene and gene product were subsequently described, but little is known about the cellular/subcellular sites of ALR synthesis in the liver, or about the release and dissemination of the peptide. To obtain this information in rats, we raised antibodies in rabbits against rat ALR for development of an enzyme-linked immunosorbent assay (ELISA). ALR concentrations were then determined in intact livers of unaltered weanling and adult rats; in regenerating residual liver after partial hepatectomy; in cultured hepatocytes and nonparenchymal cells (NPCs); and in culture medium and serum. ALR in the various liver cells was localized with immunohistochemistry. In addition, hepatic ALR and ALR mRNA were assayed with Western blotting and reverse-transcriptase polymerase chain reaction (RT-PCR), respectively. The hepatocyte was the predominant liver cell in which ALR was synthesized and stored; the cultured hepatocytes secreted ALR into the medium in a time-dependent fashion. Contrary to previous belief, the ALR peptide and ALR mRNA were present in comparable concentrations in the hepatocytes of both weanling and resting adult livers, as well as in cultured hepatocytes. A further unexpected finding was that hepatic ALR levels decreased for 12 hours after 70% hepatectomy in adult rats and then rose with no corresponding change in mRNA transcripts. In the meantime, circulating (serum) ALR levels increased up to 12 hours and declined thereafter. Thus, ALR appears to be constitutively expressed in hepatocytes in an inactive form, and released from the cells in an active form by unknown means in response to partial hepatectomy and under other circumstances of liver maturation (as in weanling rats) or regeneration.

Aging↗
PubMed1989

A dog model for acetaminophen-induced fulminant hepatic failure.

The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure.

Acetaminophen↗
PubMedDate not supplied

The effect of hepatic stimulatory substance, isolated from regenerating hepatic cytosol, and 50,000 and 300,000 subfractions in enhancing survival in experimental acute hepatic failure in rats treated with D-galactosamine.

Galactosamine induces a dose-dependent hepatic injury in rats and many other animals. The toxicity of D-galactosamine appears to be a consequence of the loss of hepatic UTP. It has previously been reported that regenerating liver cytosol is able to prevent, at least in part, the lethal effect of this substance by stimulating hepatic regeneration. Recently, we have separated a fraction using alcohol precipitation (80%) from regenerating liver cytosol and from weanling rat liver cytosol prepared in acetate buffer (100 mM, pH 6.5). We named this fraction hepatic stimulatory substance because of its ability to stimulate DNA synthesis in vivo when injected intraperitoneally in 40% hepatectomized rats and in vitro in the presence of hepatocytes isolated and maintained in monolayer cultures. The stimulatory activity of the hepatic stimulatory substance is fully evident in subfractions of molecular weight up to 300,000 and 50,000 daltons of the crude material obtained using Amicon Ultra membrane filters. The present report describes the ability of hepatic stimulatory substance and its subfractions to stimulate hepatocyte proliferation and the application of these hepatic extracts in successfully reversing the lethality of D-galactosamine-induced hepatic necrosis in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗