Mouse models to study the interaction of risk factors for human liver cancer.

Each of the risk factors for human liver cancer (aflatoxin exposure, hepatitis B virus-associated liver injury, p53 loss, p53ser249 mutation, and male sex) also increases the incidence of hepatocellular carcinoma (HCC) in mouse models of hepatocarcinogenesis. Neonatal mice, partially hepatectomized adult mice, and p53-deficient mice each have a higher hepatocyte proliferation rate, are less able to detoxify AFB1, and form more DNA adducts than do normal wild-type controls. However, transgenic hepatitis B surface antigen mice, expressing hepatitis B surface antigen under control of the albumin promoter (alb/psx), are able to detoxify AFB1 at the same level as do wild-type mice.

Cocaine and other indirect-acting monoamine agonists differentially attenuate a naltrexone discriminative stimulus in morphine-treated rhesus monkeys.

Monoaminergic drugs can modify opioid withdrawal in nonhumans, and cocaine is reported to attenuate opioid withdrawal in humans. Drug discrimination was used to examine whether s.c.

Hepatic progenitor cell lines from allyl alcohol-treated adult rats are derived from gamma-irradiated mouse STO cells.

In attempts to recharacterize several markers of putative rat liver progenitor cells, single-stage reverse transcription-polymerase chain reaction (RT-PCR) analyses failed to confirm the reported immunochemical detection of albumin, alpha(1)-fetoprotein, and cytochrome P450-1A2 in the clonal line, 3(8)#21, and the cloned derivative, 3(8)#21-EGFP (enhanced green fluorescent protein). Undetectable expression occurred whether or not both lines were cultured on or off feeder layers of gamma-irradiated mouse embryonic STO (SIM [Sandoz inbred Swiss mouse] thioguanine-resistant ouabain-resistant) cells. PCR amplification of liver progenitor cell chromosomal (rat and mouse Pigr, rat INS1, mouse INS2) and mitochondrial (rat and mouse COX1) genes revealed only mouse sequences.

Superior efficacy in suppression of heterotopic bone formation using fractionated irradiation of 5 x 2 Gy compared to a single dose of 7 Gy. An experimental study in rats.

Postoperative irradiation of the operative field is an established method to prevent heterotopic ossification in total hip arthroplasty. In this study two theoretical dose-equivalent regimens of radiation therapy were compared. Allogenic bone matrix was implanted in both thighs of 50 adult male Wistar rats to induce heterotopic ossification.

Relative efficacy of buprenorphine, nalbuphine and morphine in opioid-treated rhesus monkeys discriminating naltrexone.

Efficacy is one determinant of whether a drug is an agonist or an antagonist under a particular set of conditions. Relative efficacy among the micro opioid receptor (MOR) ligands buprenorphine, nalbuphine, and morphine was examined in monkeys dependent on morphine (3.2 mg/kg/day) or l-alpha-acetylmethadol (LAAM) (1.

The hepatocyte: heterogeneity and plasticity of liver cells.

The heterogeneity of the proliferative response of the liver to injury and during hepatocarcinogenesis implicates at least four levels of cells in the hepatic lineage which respond: the mature unipolar hepatocyte, the unipolar duct cell, a bipolar ductular progenitor cell, and a multipotent periductular liver progenitor cell of presumed extra-hepatic (bone marrow) origin (1). The original concept of "embryonal rests" as the cells or origin of cancer in adult organs (2) may be correct in the sense that progenitor cells in adult tissues that give rise to cancers may derive from circulating pluripotent stem cells.

Reduced expression of p27kip1 and increased hepatocyte proliferation in p53-deficient mice.

Livers from wild-type and p53-deficient mice were analyzed for the expression of cell-cycle regulatory proteins in an attempt to determine the mechanism for the increased proliferation of liver cells in p53-deficient mice associated with enhanced susceptibility to aflatoxin-induced liver cancer. The most striking difference found was a significant reduction of the cyclin-dependent kinase inhibitor p27(kip1) in the livers of 3-mo-old p53-/- mice, whereas only small changes were found in the expression of cyclins, cyclin-dependent kinases, and the inhibitors p21(cip1) and p16(ink4a). Relative to wild-type liver, the amounts of p27(kip1) mRNA were reduced at both 1 and 3 mo, whereas the levels of p27(kip1) protein were decreased only at 3 mo.

Cellular origin of hepatocellular carcinomas.

There are four levels of cells in the hepatic lineage which may respond to different carcinogenic regimens: (1) the mature hepatocyte, which responds to diethylnitrosamine (DEN) hepatocarcinogenesis. (2) The bile duct progenitor cells, which give rise to cholangiocellular carcinomas when the furan model is used or when hamsters infected with liver flukes (Clornorchis sinensis) are exposed to dimethylnitrosamine. (3) The ductular 'bipolar' progenitor cell which gives rise to hepatocellular carcinomas (HCC) in several N-2-acetylaminofluorene (N-2-AAF) based regimens, and (4) the periductular stem cell, which is the cell of origin of HCC induced by the choline deficiency models of hepatocarcinogenesis.

High circulating ghrelin: a potential cause for hyperphagia and obesity in prader-willi syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder occurring in 1 of 10,000-16,000 live births and is characterized by excessive appetite with progressive massive obesity as well as short stature and mental retardation. Most patients have GH deficiency and hypogonadotropic hypogonadism. The causes of the hyperphagia and abnormal GH secretion are unknown.

An improved assay for genotyping the common Alu insertion in the tissue-type plasminogen activation gene PLAT.

An improved assay for genotyping the common Alu insertion in the tissue-type plasminogen activator (PLAT) locus is described in this report. The assay is a valuable asset to clinical researchers interested in exploring disease associations with this allele. The automation and improved accuracy will facilitate future population-based studies, as well as clinical screening.

Influence of estrous cycle and estradiol on behavioral sensitization to cocaine in female rats.

The hypotheses that the estrous cycle and estradiol modulate behavioral sensitization to cocaine in female rats were assessed. In an analysis of sensitization across the estrous cycle, female rats were administered saline or cocaine (15 mg/kg) twice daily for 5 days. Sensitization developed in the intact female rats as measured by the significant increase in stimulant behaviors seen between day 1 and day 5 of treatment.

Heterologous expression of a bacterial homospermidine synthase gene in transgenic tobacco: effects on the polyamine pathway.

Homospermidine synthase (HSS) is a branch-point enzyme that links the secondary pathway (pyrrolizidine alkaloids) to primary metabolism (polyamines). Since the diamine putrescine is a precursor of homospermidine and nicotine in tobacco, we performed heterologous expression of a bacterial homospermidine synthase gene (hss)in Nicotiana tabacum and determined the effect on free and conjugated polyamine levels. The hss gene from Rhodopseudomonas viridis was placed under the control of the cauliflower mosaic virus (CaMV) 35S promoter in Agrobacterium tumefaciens Ti-plasmid in sense and antisense orientation and both hss constructs were transformed into tobacco plants.

Influence of acid-citrate-dextrose anticoagulant on blood quality in retransfusion systems after total knee arthroplasty.

The influence of acid-citrate-dextrose (ACD) anticoagulant on the blood quality was assessed in this prospective, randomized, controlled study. The clinical consequences with regard to retransfusion of drainage blood following total knee arthroplasty were evaluated. After total knee arthroplasty, retransfusion was performed utilizing a "SureTrans" retransfusion system in 81 patients.

Cocaine and amphetamine attenuate the discriminative stimulus effects of naltrexone in opioid-dependent rhesus monkeys.

This study tested the hypothesis that stimulants (indirect dopamine agonists) attenuate the discriminative stimulus of naltrexone in monkeys chronically treated with L-alpha-acetylmethadol (LAAM). Four rhesus monkeys (Macaca mulatta) received LAAM (1.0 mg/kg s.

[Ultrasound diagnosis of inflammatory diseases of the hand and elbow].

After clinical and radiological examination, ultrasound has an important place in the diagnostic procedures for patients with chronic inflammatory diseases. Synovitis and effusion of the joint can be documented. Sonography may be helpful in providing an earlier diagnosis.

The role of progenitor cells in repair of liver injury and in liver transplantation.

There are three levels of cells in the hepatic lineage that respond to injury or carcinogenesis: the mature hepatocyte, the ductular "bipolar" progenitor cell, and a putative periductular stem cell. Hepatocytes are numerous, and respond rapidly to liver cell loss by one or two cell cycles but can only produce other hepatocytes. The ductular progenitor cells are less numerous, may proliferate for more cycles than hepatocytes, and are generally considered "bipolar," i.

Derivation, characterization, and phenotypic variation of hepatic progenitor cell lines isolated from adult rats.

Liver progenitor cells (LPCs) cloned from adult rat livers following allyl alcohol injury express hematopoietic stem cell and early hepatic lineage markers when cultured on feeder layers; under these conditions, neither mature hepatocyte nor bile duct, Ito, stellate, Kupffer cell, or macrophage markers are detected. These phenotypes have remained stable without aneuploidy or morphological transformation after more than 100 population doublings. When cultured without feeder layers, the early lineage markers disappear, and mature hepatocyte markers are expressed; mature hepatocytic differentiation and cell size are also augmented by polypeptide and steroidal growth factors.

Proliferation and differentiation of ductular progenitor cells and littoral cells during the regeneration of the rat liver to CCl4/2-AAF injury.

Restoration of centrolobular injury induced by carbon tetrachloride (CCl4), when hepatocyte proliferation is inhibited by treatment with N-2-acetylaminofluorene (AAF), is accomplished by proliferation of ductular progenitor cells, that arise intraportally and extend into the liver lobule. This pattern contrasts to the restitutive proliferation of hepatocytes when AAF is not administered, and the proliferation of non-ductular periportal oval cells follows periportal necrosis induced by allyl alcohol. The expanding ducts stain for alphafetoprotein (AFP), OV-6, pan-cytokeratin (CKPan), and laminin.

Allelic loss analysis by capillary electrophoresis: an accurate, automated method for detection of deletions in solid tumors.

In this report, we describe a fast and accurate capillary electrophoresis, PCR-based method for detecting loss of allelic heterozygosity in solid tumor samples. This automated method requires small sample sizes, and data can be obtained in less than 15 min. The method is particularly powerful for uncovering deletions in tumor sample preparations containing significant normal tissue contamination.

Time-related changes of collected shed blood in autologous retransfusion after total knee arthroplasty.

A prospective study was done to determine the changes in blood quality parameters of collected drainage blood in retransfusion systems at 6 and 12 h after surgery to verify whether the blood was still suitable for retransfusion purposes for an additional 6 postoperative hours beyond the so far accepted first 6-h time window after surgery. Eighty-one patients received retransfusion within the first 6 h immediately following total knee arthroplasty. Additionally, drainage blood was collected for another 6 h using the same retransfusion system.