Timing of protooncogene expression varies in toxin-induced liver regeneration.

Hepatic expression of the protooncogenes c-fos and c-myc occurs within 2 h after partial hepatectomy, and these immediate early genes are thought to prime the hepatocytes for subsequent proliferation. To examine whether such gene activation occurred in the setting of hepatocyte proliferation after toxic liver injury, protooncogene expression was examined during the regenerative response following liver injury from carbon tetrachloride (CCl4) or galactosamine (GalN). The pattern of protooncogene expression after CCl4 mirrored that seen after partial hepatectomy, with rises in c-fos and c-myc mRNA content within 2 h, and then a rapid return to baseline levels.

Unusual patterns of Histoplasma capsulatum meningitis and progressive multifocal leukoencephalopathy in a patient with the acquired immunodeficiency virus.

Disseminated histoplasmosis (DH) and progressive multifocal leukoencephalopathy occur in acquired immunodeficiency syndrome (AIDS). At autopsy, DH patients with central nervous system involvement almost always show extensive involvement of the lungs and reticuloendothelial system in addition to the brain, and progressive multifocal leukoencephalopathy is manifest as multiple demyelinating lesions in several locations in the brain. We describe an AIDS patient with a long history of aggressively treated DH who died with DH in the brain only; fungus was not found elsewhere at autopsy.

The effects of hepatic fibrosis on Ito cell gene expression.

While Ito cells appear to be a major source of increased matrix synthesis during hepatic fibrogenesis, the cellular changes that occur in these cells during liver fibrosis have not been well delineated. In this study we examined Ito cell gene expression in isolated cells from normal rats, and rats with carbon tetrachloride-induced fibrosis, in order to better define the changes occurring in these cells during this pathologic process. Specifically, we addressed three questions: (1) which matrix genes are over expressed in Ito cells in fibrotic liver; (2) do these cells increase their expression of the fibrogenic cytokine transforming growth factor-beta 1 (TGF-beta 1); and (3) do Ito cells change their phenotype during hepatic fibrogenesis as reflected by alterations in the expression of their intermediate filament genes? Northern hybridization analysis revealed that Ito cells isolated from fibrotic livers had significant increases in mRNA levels of types I, III and IV procollagen compared to normal cells, while no increases were found in hepatocytes, and Kupffer/endothelial cells had only an increase in type I procollagen mRNA.

Selective amplification of periportal transitional cells precedes formation of hepatocellular carcinoma in SV40 large tag transgenic mice.

In a major urinary protein (MUP)-promoter/simian virus 40 (SV40)Tag transgenic mouse line (MT-D2) the liver-directed, androgen-regulated transgene expression leads to synchronized pathology resulting in a stepwise progression to multiple hepatocellular carcinomas. SV40Tag-activated replication gives rise to two different preneoplastic alterations in hepatocytes, which are characterized in detail: 1) dysplasia and finally cell death in the original hepatocyte population and 2) amplification of periportal transitional hepatocytes leading to multifocal hyperplasia and hepatocellular carcinoma. Multifocal hyperplasia, most probably the equivalent of SV40Tag-immortalization, grows confluent and leads to hepatomegaly.

Two rat models of hepatic fibrosis. A morphologic and molecular comparison.

We present a morphologic and molecular comparison of two models of hepatic fibrosis. Immune complexes are the source of insult in one model. In the other model, CCl4 induces fibrosis.

Clinical utility of liver biopsy in patients with serum antibodies to the human immunodeficiency virus.

Purpose: Patients with the acquired immunodeficiency syndrome (AIDS) frequently have liver dysfunction, which may be due to a number of causes. Determination of the patients who are likely to benefit from liver biopsy, an invasive procedure, is therefore important. In this study, the results of liver biopsy in patients with AIDS were compared to those in human immunodeficiency virus (HIV)-infected patients without AIDS.

Esophageal perforation at a Barrett's ulcer.

An alcoholic man with known reflux esophagitis and Barrett's esophagus developed fever, epigastric pain, subcutaneous crepitus, and leukocytosis from an esophageal perforation at a Barrett's ulcer. Possible risk factors for perforation in this patient included alcoholism, severe gastroesophageal reflux, corticosteroid therapy, noncompliance with antacid and H2 blocker therapy, and the presence of acid-secreting parietal cells in the Barrett's epithelium. Five cases of this complication have previously been reported in a review of the literature, which included 536 cases of Barrett's esophagus or esophageal perforation.

Gamma-interferon treatment inhibits collagen deposition in murine schistosomiasis.

Since interferons have been shown to affect the synthesis of matrix proteins such as collagen in several in vitro systems, the potential role of gamma-interferon in inhibiting hepatic fibrosis was investigated. Hepatic cells, consisting primarily of hepatocytes, were treated with recombinant gamma-interferon for 24 hr. Northern blot hybridization showed that gamma-interferon treatment caused a profound decrease in pro-alpha 2(I)collagen mRNA levels but an increase in beta-actin mRNA content.

Terminal ileitis associated with cytomegalovirus and the acquired immune deficiency syndrome.

A 41-yr-old homosexual male had cytomegalovirus infection localized to the terminal ileum as his initial and sole evident opportunistic infection due to the acquired immune deficiency syndrome. The symptoms, signs, roentgenographic findings, and appearance at surgery were suggestive of Crohn's disease. The pathogen was identified only by microscopic examination of bowel resected during a second laparotomy.

In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis.

Despite extensive efforts, little progress has been made in identifying the factors that induce hepatic fibrosis. Transforming growth factor-beta (TGF-beta) has been shown to enhance collagen production, therefore its role in hepatic fibrosis was investigated. Treatment of cultured hepatic cells with TGF-beta 1 increased type I procollagen mRNA levels 13-fold due to post-transcriptional gene regulation.

Expression of tumor necrosis factor-alpha and transforming growth factor-beta 1 in acute liver injury.

Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta 1) have a number of in vitro functions that could be important in vivo in acute liver injury and repair. Therefore, we investigated these two cytokines in acute liver damage. Northern blots of RNA isolated from rats sacrificed at various time intervals after a single oral dose of CCl4 revealed that TNF-alpha mRNA levels were elevated within 6 hr of CCl4 administration and returned to control values by 24-32 hr.

Morphologic and chemical studies on a murine mutation (toxic milk mice) resulting in hepatic copper toxicosis.

The accumulation of excessive amounts of copper in the livers of toxic milk mice results in gross morphologic, histologic, and ultrastructural changes that are progressive with age even though the concentrations of copper tend to decrease in mice older than 6 months. Striking differences in morphologic integrity between regenerative nodules and the intervening parenchyma were observed. Profound changes in mitochondria, endoplasmic reticulum, and nuclei as well as accumulation of microvesicular lipid droplets were observed in injured hepatocytes.

Insulinlike growth factor II expression and oval cell proliferation associated with hepatocarcinogenesis in woodchuck hepatitis virus carriers.

Insulinlike growth factor II (IGF-II) is a highly mitogenic fetal growth factor suspected of regulating the growth of a wide spectrum of tissues via an autocrine or paracrine mode of action or both. High steady-state levels of IGF-II RNA were detected in 45% of hepatocellular carcinomas (HCCs) arising from woodchuck livers with persistent woodchuck hepatitis virus (WHV) infection. Analysis of WHV RNA in the same HCCs revealed that HCCs with high levels of IGF-II RNA contained low or undetectable levels of WHV RNA and HCCs with low levels of IGF-II RNA contained high levels of WHV RNA.

Changes in albumin, alpha-fetoprotein and collagen gene transcription in CCl4-induced hepatic fibrosis.

In efforts to understand mechanisms of liver dysfunction in cirrhosis, transcription of specific genes important to liver function has been measured in the rat model of CCl4-induced hepatic fibrosis. The relative transcription rates of albumin, alpha-fetoprotein and pro-alpha 1-collagen genes were studied during development of fibrosis and after fibrosis was established. During the initial phase of CCl4 administration, there was a decrease in albumin transcription associated with increased alpha-fetoprotein transcription, indicative of active liver regeneration.

Transcriptional and posttranscriptional effects of dexamethasone on albumin and procollagen messenger RNAs in murine schistosomiasis.

We have previously shown that dexamethasone increases albumin mRNA and decreases procollagen steady-state mRNA levels in rat hepatocyte cultures. These studies were extended by evaluating an in vivo model of fibrogenesis (murine schistosomiasis) and by determining a more precise level of gene expression responsible for these changes. Control mice and litter mates infected with Schistosomiasis mansoni were evaluated at 8 weeks postinfection when the livers of the infected mice had become fibrotic and their serum albumin levels significantly decreased.

Collagenase and elastase production by mouse mammary adenocarcinoma primary cultures and cloned cells.

We have shown previously that an increase in tumor invasion and metastases occurred concurrently with a decrease in collagen content of the extracellular matrix surrounding the C3H mouse mammary adenocarcinoma borne by C3H/HeJ mice. In this paper we report the production of collagenase and elastase activities by the primary tumor cultures and three types of cloned C3H mouse mammary adenocarcinoma cell cultures. The primary tumor cell cultures and tumor-associated stromal cultures produced large amounts of collagenase and elastase activities.

Transcriptional switch from albumin to alpha-fetoprotein and changes in transcription of other genes during carbon tetrachloride induced liver regeneration.

During liver regeneration induced by CCl4 administration to rats, changes in the relative transcription rates of albumin and alpha-fetoprotein genes have been measured in conjunction with other liver-specific and general cellular function genes. Within 24 h following CCl4 administration, albumin gene transcription decreases by 85%, whereas alpha-fetoprotein transcription increases from undetectable levels to 50% of that observed for albumin. These changes precede maximal [3H]thymidine incorporation into DNA which peaks at 48 h.

Effects of vitamin A and dexamethasone on collagen degradation in mouse mammary adenocarcinoma.

Collagenases and other neutral proteases in tumors may facilitate tumor extension, invasion, and subsequent metastasis. We report the effects of vitamin A and dexamethasone, known inhibitors of collagenase production in vitro, on the collagen metabolism of mouse mammary adenocarcinoma and its capsule, borne by C3H/HeJ mice. The weight of the capsule was about 4% of the tumor, yet the total collagen content of the capsule was about 10-fold greater than that of the tumor tissue; tumor cells had no detectable collagen.

Bile duct carcinoma in an adolescent.

Bile duct carcinoma is a relatively uncommon lesion that usually presents in the 6th to 7th decade. The only prior reported cases under the age of 20 were two patients with diseases known to predispose to the development of this tumor. We report a case of a 17-year-old girl with a bile duct tumor without any known predisposing factors.

Regulation of growth and differentiation of a rat hepatoma cell line by the synergistic interactions of hormones and collagenous substrata.

Serum-free, hormonally defined media have been developed for optimal growth of a rat hepatoma cell line. The cells' hormonal requirements for growth are dramatically altered both qualitatively and quantitatively by whether they were plated onto tissue culture plastic or collagenous substrata. On collagenous substrata, the cells required insulin, glucagon, growth hormone, prolactin, and linoleic acid (bound to BSA), and zinc, copper, and selenium.

Infiltrating periductal neoplasm mimicking biliary dilatation on computed tomography.

A case is reported in which hypodense linear structures on postcontrast computed tomography were not intrahepatic biliary dilatation but periductal extension of pancreatic carcinoma.

Rat liver canalicular membrane vesicles. Isolation and topological characterization.

Canalicular plasma membranes were isolated from rat liver homogenates using nitrogen cavitation and calcium precipitation methods. Compared with homogenates, the membranes were enriched 55- to 56-fold in gamma-glutamyltransferase, aminopeptidase M, and alkaline phosphatase activities and showed very low enrichment in markers of other membranes. By electron microscopy, the membrane preparation contained neither junctional complexes nor contaminating organelles and consisted exclusively of vesicles.

Immunohistochemical localization of collagenase in hepatic murine schistosomiasis.

It has been previously demonstrated that collagenase activity and collagen synthesis in hepatic granulomas of mice infected with S. mansoni cercariae are maximal 8 weeks after infection; however, total liver collagen content continues to increase. Now the anatomic relationships among collagenase and collagen, granulomas, and hepatic parenchyma in normal mice and in mice infected with S.

Liver collagen-type characterization in human schistosomiasis. A histological, ultrastructural, and immunocytochemical correlation.

Liver biopsies of four patients with hepatosplenic schistosomiasis, two patients with schistosomiasis and chronic active hepatitis, two patients with chronic active hepatitis and four control patients with no clinical evidence of either disease, were examined by standard light microscopic techniques, electron microscopy and immunocytochemical staining for collagen type I, III and B. Pure schistosomiasis showed the classical "clay-pipe stem fibrosis" and granulomata composed of eosinophils, macrophages and lymphocytes. In that group, the hepatocellular damage was less conspicuous than in the groups with chronic hepatitis and was usually confined to the granulomatous or fibrotic areas.