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S Sell

Publications and source records attributed to S Sell.

At least 181 records · Page 10Linked to original sources

Induction of foci of altered, gamma-glutamyltranspeptidase-positive hepatocytes in carcinogen-treated rats fed a choline-deficient diet.

A series of experiments was performed to investigate whether, after exposure of rats to a chemical hepatocarcinogen, feeding a choline-deficient (CD) diet would promote the proliferation of initiated liver cells, and their evolution to foci of altered γ-glutamyltranspeptidase (GGT)-positive hepatocytes, without subjecting the animals to further experimental manipulations.Diethylnitrosamine (DEN), in single doses of 15-150 mg/kg body weight, was injected into male, Sprague-Dawley rats, either intact or 18 h after a partial hepatectomy (PH). The animals were then fed either a CD or a choline-supplemented (CS) diet for 2-8 weeks. Emergence in the liver of foci of altered, GGT+ hepatocytes was studied by histological and histochemical techniques. Foci, in varying numbers, developed in the liver of all rats fed the CD diet. The number of foci induced was larger when DEN was administered after PH rather than to intact rats. Foci developed in none of the livers of rats fed the CS diet, except in one experiment in which 30 mg DEN/kg body weight was injected after a PH. In all cases, foci of altered, GGT+ hepatocytes were shown to be α-foetoprotein after immunofluorescence staining of liver sections.It is concluded that feeding a CD diet exerts a strong promoting action on the proliferation and further evolution of liver cells initiated by a chemical carcinogen, providing the basis for a new and efficient procedure for the induction of foci of altered hepatocytes in rat liver.

Animals↗

alpha-Fetoprotein and albumin genes of rats: no evidence for amplification-deletion or rearrangement in rat liver carcinogenesis.

Full-length radiolabeled albumin and alpha-fetoprotein (AFP) cDNAs were synthesized from pure albumin and AMP mRNA preparations by using avian myeloblastosis virus reverse transcriptase (RNA-dependent DNA polymerase). The cDNAs have been used to quantitate the number of albumin and AFP genes in different rat tissues by two independent methods, both of which yielded similar results. First, the kinetics of the association of these cDNAs with nuclear DNA from rat liver, rat kidney, and Morris hepatoma 7777 under conditions of vast DNA excess indicated that the albumin and AFP mRNA's are transcribed from "nonrepetitive DNA." Second, saturation hybridization experiments in which a constant amount of rat liver DNA or Morris hepatoma 7777 was hybridized with increasing amounts of cDNA to albumin mRNA have shown the presence of 1--2 albumin genes per rat haploid genome. The number of AFP genes obtained in similar titration experiments was approximately 2--3. This was true whether rat liver DNA or hepatoma 7777 DNA was used in the reassociation experiments. When high molecular weight DNA preparations from both these tissues were digested with the restriction endonuclease EcoRI and the fragments were transferred to a nitrocellulose filter, the albumin and AFP [32P]cDNA probes hybridized to different sets of DNA fragments. However, each probe gave the same hybridization pattern whether Buffalo rat liver DNA or hepatoma 7777 DNA was utilized.

Albumins↗

Dissociation of alpha-macrofetoprotein and alpha-fetoprotein production during experimental injury.

The concentrations of two major fetal serum proteins of the rat, alpha-macrofetoprotein (AMF) and alpha-fetoprotein (AFP) are measured following administration of croton oil, carbon tetrachloride, galactosamine or ethionine, and after partial hepatectomy. Greatly elevated serum concentrations of AMF are found after croton oil injection, following oral administration of CCl4, and after partial hepatectomy, but not after ethionine or galactosamine. Elevations of AFP occur after administration of hepatotoxic agents during the stage of restitutive proliferation and after exposure to the hepatocarcinogen ethionine, but not after croton oil. Therefore, elevations of AMF and AFP are clearly dissociated under certain conditions. In situations such as partial hepatectomy, after which elevations in both AMF and AFP occur, AMF appears before AFP. Therefore, the production of AMF and AFP appear to be under completely independent regulation in the adult.

Animals↗

alpha-Fetoprotein levels and hepatic alterations during chemical carcinogenesis in C57BL/6N mice.

Hepatocellular carcinomas were induced by administration of acetylaminofluorene or chlordane to C57BL/6N mice. Lesions which closely resembled the neoplastic nodule described as a putative premalignant lesion in rats were evident. alpha-Fetoprotein elevations were noted only in the presence of the malignant lesions for both carcinogens. In this regard, the responses of these mice were similar to those seen during spontaneous hepatocarcinogenesis.

2-Acetylaminofluorene↗

Rat alpha-macrofetoprotein (acute-phase alpha 2-macroglobulin) during hepatocarcinogenesis.

Rat alpha-macrofetoprotein (AMF) and alpha-fetoprotein (AFP) are secreted by the fetal liver and become elevated in serum during hepatocarcinogenesis and in animals bearing hepatocellular carcinomas. It has been suggested that these fetal plasma proteins may be influenced by related control mechanisms. The experiments presented herein examined the early responses of these plasma proteins during hepatocarcinogenesis using the hepatocarcinogens acetylaminofluorene and diethylnitrosamine. Under these conditions, AFP serum concentrations were elevated within a few days of exposure to acetylaminofluorene, whereas AMF serum concentrations remained essentially normal. AFP became elevated after a number of weeks of exposure to diethylnitrosamine. In either regimen, AMF became elevated only later when large primary hepatocellular carcinomas were found. The time of appearance of AMF after transfer of an AFP-secreting Morris hepatoma indicated that AMF was elevated only in animals with extremely large, necrotic tumors. Thus, it appears that elevation of serum AFP resulted from either exposure to hepatocarcinogens or production by hepatocellular carcinomas, but that the elevations of serum AMF levels resulted from inflammatory injury or necrosis of tumor tissues.

2-Acetylaminofluorene↗

Serum concentrations of alpha-macrofeto-protein (acute-phase alpha2-macroglobulin), a proteinase inhibitor, in pregnant and neonatal rats and in rats with acute inflammation.

Alpha macrofetoprotein (AMF) or acute-phase alpha2 macroglobulin serum concentrations are elevated in pregnant, fetal, and newborn rats and in rats with experimentally induced acute inflammation when quantitated using a double-antibody radioimmunoassay. Concentrations of AMF are 17 +/- 2 microgram/ml and 32 +/- 6 microgram/ml in normal adult rat sera. Both maternal (1.2 mg/ml) and neonatal (9.3 mg/ml) concentrations are maximal at term. AMF serum concentrations of rats injected with croton oil into the hind footpads are unchanged for the first 4 h after injection, then increase to a maximum of 10.5 mg/ml 36 h after injection. Serum AMF concentrations correlate directly with the dose of croton oil and the increase in size (swelling) of the injured foot, and remain elevated during the course of inflammation for at least two weeks. The possible function of AMF as an antiproteinase limiting the extent of inflammation after acute tissue injury is discussed.

Aging↗

Tumor immunity: relevance of animal models to man.

The conclusions that can be drawn from results of animal experiments often provide important insights into the mechanisms of human disease and the rationale for effective therapy. A few years ago, animal models of tumor immunity revealed that both specific and nonimmune specific stimulation of the immune system could effectively prevent or cure cancer. Extensive clinical studies have not convincingly demonstrated that the results with the animal models used are reproducible in humans. New animal models more closely reflecting the properties of human cancer are needed to determine the applicability of cancer immunotherapy to man.

Animals↗

Ultrastructural labeling of lymphocyte surface immunoglobulin: the preparation and use of soluble immune complexes as indirect immunoelectromicroscopic markers.

2 distinct macronuclear markers, ferritin and hemocyanin, may be used in a mixed anti-globulin labeling reaction to localize lymphocyte surface immunoglobulin (Ig) determinants by transmission electron microscopy. Soluble immune complexes of the marker molecules (antigen) are prepared by complexing with specific antiserum in 40 to 50 x antigen excess; uncomplexed Ig is removed by ultrascentrifugation and/or gel filtration chromatography. Immunoelectrophoresis, spectrophotometry and passive hemagglutination inhibition assay are used to determine the purity and amounts of antibody-antigen in the purified immune complexes. For immunoelectron microscopic labeling, the immune complex markers are coupled to lymphocyte surface Ig by an indirect anti-Ig or anti-allotype antibody linkage. Labelled Ig determinants at 0 degrees C or in the presence of sodium azide are visualized as small patches of marker molecules on the lymphocyte surface membrane. This EM labeling method results in much more consistent and generally higher percentages of surface Ig positive cells (60 to 70% of rabbit peripheral blood lymphocytes) than the percentages obtained using other methods, such as immunofluorescence or autoradiography. If the lymphocytes are warmed to 37 degrees C in the absence of azide the labeled surface Ig determinants undergo rapid endocytosis; endocytotic vesicles containing marker molecules are visible. This mixed anti-globulin immunoelectronmicroscopic labeling system may be used to localize a wide variety of antigens on different cell surfaces.

Animals↗

Growth state-dependent phenotypes of adult hepatocytes in primary monolayer culture.

A proliferation-competent adult rat liver cell monolayer system has been analyzed for tissue-specific functions during its growth cycle. High levels of the adult (L type) form of pyruvate kinase (EC 2.7.1.40) and glutathione S-transferase B ("ligand," EC 2.5.1.18) are observed during the early lag phase; they decline markedly during the logarithmic phase and reappear during the stationary phase. By contrast, elevated levels of the fetal (K type) form of pyruvate kinase and alpha1-fetoprotein production appear only after proliferation begins; this pattern diminishes slightly during stationary phase as the adult phenotype is restored. Albumin production continues throughout the entire growth cycle. These in vitro findings simulate those observed during hepatoproliferative transitions in the intact animal and, as such, constitute a developmental program for normal epithelial cells in primary culture.

Albumins↗