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 reversetranscriptase 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 timedependent 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. (HEPATOLOGY 1999;29:1435-1445.)The control of hepatic growth and regeneration has interested experimentalists for much of the 20th century. 1 Soon after the classical description in 1931 by Higgins and Anderson 2 of liver regeneration in rats following 70% hepatectomy, a search began for growth factors within the liver itself. McJunkin and Breuhaus 3 observed that the modest mitotic response to a 30% to 40% hepatectomy in rats was enhanced with an intraperitoneal injection 2 days postoperatively of homogenized homologous rat liver. Two decades later, Teir and Ravanti 4 and Blomquist 5 noted that this ''augmentation'' effect was demonstrable only when the injected homogenates were prepared from regenerating liver fragments following hepatectomy or from weanling rat livers that have a naturally heightened mitotic index. Subsequently, LaBrecque and Pesch 6 reported the same prerequisite of a hyperplastic liver source for cytosol extracts containing a putative ''hepatic stimulatory substance'' (HSS).Importantly, however, a cocondition for demonstrating a mitosis-augmenting a...

Infected-cell polypeptide 4 (ICP4) of herpes simplex virus type 1 (HSV-1) is both a repressor and an activator of RNA polymerase II (Pol II) transcription. ICP4 is expressed immediately after viral infection and is essential for viral lytic growth (8, 14, 52) because of its role in the transcriptional activation of most viral early and late genes (9,15,21,48,54,65). Like many other transcriptional activators, ICP4 is composed of discrete functional domains including transactivation, repression, dimerization, nuclear localization, and DNA binding (10,11,50,51,60). ICP4 is a very large protein, existing in cells as an elongated 61). It is a sequence-specific DNA-binding protein (17,39,46) because of a DNA binding domain that contains a helix-turn-helix motif (60). The repressing activity of ICP4 has been most clearly demonstrated by the autoregulation of its own expression (9, 49, 57). The promoter for ICP4 contains a strong ICP4 binding site near the transcription start (18,39,46). Studies using transient expression assays, mutant viruses, and in vitro transcription assays have shown that ICP4 represses transcription of its own promoter as a function of this site (9,25,45,49,56). However, the exact mechanism of transcription inhibition by ICP4 is unclear.Accurate transcription by Pol II requires a number of general transcription factors, including TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH (4, 71). The assembly of transcription initiation complexes by the general transcription factors follows the binding of TFIID to the promoter TATA box, which results in a committed complex (4, 66). TFIID is a large multisubunit protein complex consisting of the TATA boxbinding protein (TBP) and at least 8 TBP-associated factors (TAFs) (34, 72). The addition of TFIIA, TFIIB, Pol II-TFIIF, and subsequently TFIIE and TFIIH forms the complete initiation complex (4, 71). TFIIB interacts with TBP and Pol II and is responsible for the recruitment of Pol II to the complex (27). Modulation of Pol II gene transcription involves both transcription activation and repression. In vitro reconstitution of transcription with highly fractionated and purified recombinant transcription factors has demonstrated that TBP, together with other general factors, is sufficient to direct accurate basal transcription while TFIID is required for activation by specific factors (53,64). Communication or interaction with TAFs or coactivators is required for activation by specific activator proteins. It has previously been shown that ICP4 also requires coactivators to stimulate transcription (24). Although the specific activator-TAF interactions have been clearly shown to be involved in the communication between the activators and the transcription machinery, how the communication affects the transcription machinery and leads to transcription enhancement is still unknown.Consistent with the multistep nature of the transcription process, repression of transcription can also occur at multiple steps. Repression of transcription can occur at either the basal or t...

No abstract

No abstract

No abstract

Although longer patient follow-up is required and mandated to unequivocally establish the biosafety of this device and related bioartificial organ systems, these analyses support the conclusion that when used under standard operational conditions, the BLSS is safe.

No abstract

Background: The aim of the study was to investigate any associations between benign prostate hyperplasia (BPH) and single nucleotide polymorphisms (SNPs) in the VDR gene (FokI, BsmI, ApaI and TaqαI loci) and the CYP17 gene (MspA1I locus), as well as TA repeat polymorphism in SRD5A2 gene among Lebanese men. Materials and Methods: DNA extracted from blood of 68 subjects with confirmed BPH and 79 age-matched controls was subjected to PCR/PCR-restriction fragment length polymorphism analysis. The odds ra=tio (OR) of having a genotype and the relative risk (RR) of developing BPH for having the genotype were calculated and the alleles were designated risk-bearing or protective. Results: Our data indicated that the A and B alleles of the VDR ApaI and BsmI SNPs were highly associated with increased risk of BPH (p=0.0168 and 0.0002, respectively). Moreover, 63% of the controls compared to 43% of the subjects with BPH were homozygous for none of the risk-bearing alleles (p=0.0123) whereas 60% of the controls and 28% of the subjects with BPH were homozygous for two or more protective alleles (p<0.0001). Conclusions: For the first time, our study demonstrated that ApaI and BsmI of the VDR gene are associated with risk of BPH among Lebanese men. Our study also indicated that overall polymorphism profile of all the genes involved in prostate physiology could be a better predictor of BPH risk.