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Biomedical subjects

G M Fuller

Publications and source records attributed to G M Fuller.

At least 73 records · Page 4Linked to original sources
PubMed1985

Corticotropin-releasing activity of monokines.

Hepatocyte-stimulating factor and interleukin-1 are proteins produced by monocytes in response to inflammatory challenge. Neither of these monokines had direct effects on steroid production by cultured adrenocortical cells. Both monokines stimulated pituitary cells (AtT-20) to release adrenocorticotropic hormone; interleukin-1 was equipotent with a combination of corticotropin-releasing factor and arginine vasopressin, and hepatocyte-stimulating factor was at least three times as effective. The synthetic glucocorticoid, dexamethasone, inhibited production of hepatocyte-stimulating factor by cultured monocytes. These results indicate an axis between monocytes and pituitary and adrenocortical cells which may play a role in regulating host defense.

Adrenal Glands↗
PubMed1985

Identification and partial characterization of hepatocyte-stimulating factor from leukemia cell lines: comparison with interleukin 1.

Leukemia cell lines of the monocytic series (HL-60, U-937, and P388D1) produce a hepatocyte-stimulating factor (HSF) following induction of differentiation with phorbol diester. In 24-72 hr, these leukemia cells produce 2-30% the amount of HSF as human peripheral blood monocytes. Cells of the series at earlier stages of differentiation produced greater amounts of HSF. Fractionation of the medium from each cell type by HPLC reveals much of the HSF activity in the 25- to 30-kilodalton range. Under the same culture conditions, interleukin 1 is produced; however, its bioactivity is in the 7- to 15-kilodalton range. Neither monokine shows reciprocal bioactivity. Superinducing culture conditions that greatly increase interleukin 1 production completely eliminate HSF production, suggesting that there is different stability of the mRNA coding for each protein or that there are different temporal events important to the induction of synthesis of these proteins.

Animals↗
PubMed1985

The effects of hepatocyte stimulating factor on fibrinogen biosynthesis in hepatocyte monolayers.

The biosynthesis of fibrinogen increased at least eightfold in primary hepatocytes when incubated in the presence of monocyte/macrophage-derived hepatocyte stimulating factor (HSF). The large increase in fibrinogen production is due to increased availability of the mRNAs for the protein since cytodot analysis of cellular RNA showed a 10-12-fold increase in each of the fibrinogen mRNAs. Pulse-chase experiments showed that the time for fibrinogen synthesis, assembly, and secretion was 40-50 min for both control and stimulating conditions. This indicates that the increased production was due principally to the presence of greater amounts of fibrinogen mRNA rather than translation or secretion-specific events. Three lines of evidence indicate that the increase in fibrinogen production was due to HSF effects on transcription: (a) analysis of cytoplasmic levels of each of the fibrinogen mRNAs showed that all three increased at the same rate and to the same extent, demonstrating that HSF affects the three gene products coordinately; (b) Northern gel analysis of cytoplasmic RNA isolated after very brief exposures to HSF showed increases in a large molecular weight fibrinogen RNA precursor; and (c) actinomycin D blocked the HSF-stimulated increase in fibrinogen mRNA species. Furthermore, experiments in which protein synthesis was inhibited by cycloheximide failed to inhibit the increase in fibrinogen mRNAs, indicating new protein synthesis is not required for the HSF stimulation of fibrinogen mRNA. These results are consistent with our hypothesis that HSF is exerting its control of fibrinogen at the level of gene transcription.

Animals↗
PubMed1983

Kupffer cell regulation of fibrinogen synthesis in hepatocytes.

Isolated rat liver macrophages (Kupffer cells) produce a factor(s) which stimulates fibrinogen synthesis 5-8 fold in hepatocyte cultures. The production of the stimulatory factor reached maximum during the first 24 hours the cells were in culture. When the cell culture medium was chromatographed on a calibrated Sephadex G-75 column the major activity peak eluted in the size range of 25,000-30,000 daltons. Taken together these results demonstrate that in addition to their well known phagocytic function, Kupffer cells secrete factor(s) that can significantly increase fibrinogen synthesis.

Animals↗
PubMed1983

Translational and cotranslational events in fibrinogen synthesis.

What we have shown in these studies are some of the first steps in the assembly of fibrinogen. We believe that using the hepatocyte culture system together with molecules capable of stimulating an increase in synthesis holds much promise in helping to learn how the cell puts together this elegant and complicated molecule. Moreover, these studies may also provide clues to mechanisms operant for other complex proteins produced by the liver.

Amino Acid Sequence↗
PubMed1982

Haptoglobin biosynthesis in rats. Immunological identification of polysomes synthesizing haptoglobin and quantitation of haptoglobin in the cytoplasm of liver cells.

A quantitative enzyme-linked immunosorbent assay was developed and utilized to study the stimulation of haptoglobin biosynthesis during an acute inflammatory challenge. A 10-fold increase in intracellular haptoglobin was measured at the peak of the inflammatory response. The increase in serum haptoglobin levels was concomitant with the intracellular levels, demonstrating the secretory output is also elevated during the inflammatory period. A monospecific antihaptoglobin was produced and used to detect the specific polysomes involved in haptoglobin synthesis. The amount of radioactively labeled antibody bound to the nascent haptoglobin chain was increased approx. 3-fold during the inflammatory response, indicating that new haptoglobin was being synthesized and suggesting an increase in functional haptoglobin mRNA resulting from the inflammatory signal.

Animals↗
PubMed1982

Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: an indirect feedback pathway.

The effect of plasmin-derived fibrinogen fragments on the biosynthesis of fibrinogen was investigated in cultured monolayers of rat hepatocytes. Incubating the cells with several concentrations of either fibrinogen or fibrin fragment D or E had no effect on the synthesis and secretion of fibrinogen by these cells. However, if the fragments were incubated with isolated peripheral blood leukocytes, they caused these cells to secrete a factor that when added to the hepatocytes caused an increase in fibrinogen synthesis 4- to 6-fold over controls. Moreover, the hepatocyte-stimulating factor also affected the production of several other proteins produced by the hepatocyte. These results demonstrate that both fragments D and E can stimulate hepatic fibrinogen synthesis via an indirect leukocyte-mediated pathway.

Animals↗
PubMed1981

Modification of fibrinogen chains during synthesis: glycosylation of B beta and gamma chains.

Specific immunoprecipitation and affinity chromatography on Con A-Sepharose of in vitro translated products derived from rat liver messenger ribonucleic acid (mRNA), total polysomes, and rough microsomes have been used to determine temporal events of glycosylation of the subunits of fibrinogen. The A alpha chain is not glycosylated, whereas both the B beta and the gamma chains have carbohydrate clusters (probably Asn linked). Evidence presented here shows that the gamma chain receives its core carbohydrate as an early cotranslational event. The B beta chain is glycosylated later and likely is glycosylated at the time of polypeptide termination or shortly after it is released from the ribosome into the cisternal space of the rough endoplasmic reticulum.

Animals↗
PubMed1981

An in vitro bioassay for leukocytic endogenous mediator(s) using cultured rat hepatocytes.

Primary cultures of adult rat hepatocytes were used to assay for the presence of leukocytic mediator(s) (LEM), a neutrophil derived protein(s) capable of stimulating the synthesis of acute-phase plasma proteins when injected into rats. In the presence of physiological concentrations of dexamethasone (40 mM), the hepatocytes secreted a variety of plasma proteins as demonstrated by crossed immunoelectrophoresis. The addition of LEM to hepatocytes increased the secretion of several acute-phase related plasma proteins, including fibrinogen and hepatoglobin, and decreased albumin secretion. These results mimic the acute-phase response observed in the intact animal. Fibrinogen secretion was used as a quantitative marker for determining LEM activity. The rate of fibrinogen secretion depended upon both the concentration of dexamethasone and LEM present during a given 24-h assay period. One unit of LEM activity is defined as that concentration of LEM capable of producing a 50% maximal stimulation of fibrinogen secretion.

Animals↗
PubMed1981

In vitro synthesis of rat fibrinogen: identification of preA alpha, preB beta, and pre gamma polypeptides.

Vertebrate fibrinogen consists of two sets of three nonidentical polypeptides that are synthesized in the liver. The subunits of fibrinogen have been synthesized in a cell-free, membrane-free translation system and compared with (alpha), polypeptides of fibrinogen purified from rat plasma and (b) subunits synthesized and secreted by hepatoma cells grown in culture. Rat hepatoma monolayers were grown with or without tunicamycin to prevent or allow glycosylation of the B beta and gamma subunits, respectively. Sodium dodecyl sulfate polyacrylamide gel analysis indicated that each of the polypeptides translated in vitro from mRNA is larger than its corresponding nonglycosylated fibrinogen chain. The primary translation A alpha, B beta, and gamma chains are larger than their authentic nonglycosylated counterparts by 600, 1100, and 3000 daltons, respectively. Furthermore, the preA alpha and preB beta translation products are thrombin sensitive. These results strongly imply that signal peptides exist on each of the primary translation products of fibrinogen.

Animals↗
PubMed1980

Plaminogen is synthesized by primary cultures of rat hepatocytes.

The accumulation of rat plasminogen in the medium of primary monolayer cultures of adult parenchymal hepatocytes was detected with a quantitative immunological assay. These primary cultures synthetisized and secreted both circulating isozymic forms of plasminogen at rates sufficient to account for the majority of the in vivo plasminogen turnover.

Animals↗
PubMed1978

Are lobster fibrinogen and cold-insoluble globulin related molecules?

Several of the molecular properties of lobster fibrinogen and CIg have been compared. There are some significant similarities between these two proteins; however, to date, no direct experiments have demonstrated molecular homologies. Studies involving cyanogen bromide mapping, additional immunologic probing, and modifications of cell morphology effected by lobster fibrinogen are currently in progress. It is anticipated that these and other experimental approaches will provide direct evidence to answer the question, posed by the title of this paper.

Amino Acids↗