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Biomedical subjects

G Feldmann

Publications and source records attributed to G Feldmann.

At least 199 records · Page 11Linked to original sources
PubMed1987

Quantitation of hepatic sinusoidal macrophages during the acute systemic inflammatory reaction in two animal species.

The participation of hepatic sinusoidal macrophages (HSM) in hepatocyte stimulation during the acute systemic inflammatory reaction has been suggested by recent in vitro investigations. A first attempt in studying the role of these cells in vivo would appear to be the quantitation of HSM at the different times of the inflammatory response, in order to determine whether the participation of HSM depends on the recruitment of blood monocytes to the liver or on the proliferation of resident cells. HSM were counted during the initial stages (0, 16, and 24 hr) of a turpentine-induced inflammation in the rat and the rabbit. They were identified on morphological grounds and were counted separately in the periportal and the perivenous areas of the hepatic lobule. No significant differences were found in the number of HSM per field at 0, 16, and 24 hr following the induction of inflammation. No variation in the distribution of these cells within the lobule could be detected during this period. These results do not support the hypothesis that the acute phase reaction is accompanied by an influx into the liver of newly recruited macrophages or by the proliferation of resident cells. Thus, if a commitment of HSM occurs in vivo during the acute systemic inflammation, it may depend on the activation of resident cells.

Acute Disease↗
PubMed1986

Correlation between plasma membrane surface area and transferrin secretion rate in isolated hepatocytes.

It is generally considered that in exocytosis the size of the secreting cells does not increase when the membranes of exocytosis vesicles fuse with the plasma membrane. As the factors involved in the regulation of this phenomenon are poorly understood, we thought it worthwhile to investigate the relationship between the plasma membrane surface area and secretory activity. Isolated rat hepatocytes were prepared by liver collagenase perfusion. Secretion of the plasma protein, transferrin (Tf) was detected at the single cell level with specific anti-rat transferrin antibodies using the reverse hemolytic plaque test. Hepatocyte surface and hemolytic ring surface areas were calculated from diameters of hepatocyte and hemolytic plaque measured after 5h of incubation. A highly significant correlation was established between the plaque-forming hepatocyte surface areas and the corresponding hemolytic surface areas. This result was confirmed using an automatic image analysis method. Two-month-old rats were compared to 4-month-old rats. We observed that the ratio of the quantity of transferrin secreted by hepatocytes to the hepatocyte surface area was constant for a given incubation time, whatever the size of the hepatocytes. These results suggest that the plasma membrane surface area of hepatocytes may constitute a limiting factor in Tf secretion.

Aging↗
PubMed1986

Inhibitory effect of the acute inflammatory reaction on liver regeneration after partial hepatectomy in the rat.

We evaluated the influence of an acute inflammatory reaction that triggers the synthesis of exportable proteins by hepatocytes on liver regeneration after partial hepatectomy, which induces the synthesis of proteins necessary for liver cell proliferation. In hepatectomized rats with a turpentine-induced acute inflammatory reaction, the first peaks of hepatic DNA synthesis and mitosis were significantly inhibited compared with pair-fed controls subjected to partial hepatectomy only, and the liver DNA concentration at various times after partial hepatectomy was significantly lower in the former than in the latter. Inhibition was not obtained when the acute inflammatory reaction was induced 12 h or more before partial hepatectomy, suggesting that the inhibitory effect of turpentine administration depended on early events in the acute inflammatory reaction. These data suggest that one possible mechanism responsible for inhibition of regeneration might be competition at the transcriptional or the translational level between liver syntheses of various proteins, and that, under certain conditions, liver-specific functions might take precedence over regenerative functions.

Acute Disease↗
PubMed1986

Prolonged cholestasis after ajmaline-induced acute hepatitis.

We report the cases of 3 patients in whom ajmaline-induced acute hepatitis was followed by anicteric cholestasis persisting for more than 1 year after cessation of administration of the drug. Ajmaline was given for 8-16 days before the onset of acute hepatitis. Jaundice was preceded by fever, chills and abdominal pain, and was associated with hypereosinophilia. The initial lesions included centrilobular cholestasis and portal inflammatory infiltration. Jaundice lasted for 3 weeks to 11 months. In these 3 patients liver tests were still abnormal 17-26 months after ajmaline withdrawal; histological examination, performed 9-26 months after the onset of jaundice, showed a decreased number of interlobular bile ducts, ductular proliferation, and mild portal fibrosis; circulating immune complexes were demonstrated. These observations demonstrate that prolonged cholestasis can follow ajmaline-induced acute hepatitis. Persistence of cholestasis long after the withdrawal of ajmaline suggests some form of autoimmunity.

Acute Disease↗
PubMed1986

Cellular analysis by in situ hybridization and immunoperoxidase of alpha-fetoprotein and albumin gene expression in rat liver during the perinatal period.

To analyze at the cellular level the decrease in alpha-fetoprotein (AFP) gene expression during the early postnatal growth, we searched for AFP gene transcripts by in situ hybridization using a specific cDNA probe, and for the corresponding protein by immunocytochemistry, on rat liver sections at various times of the perinatal period. The relative number of mRNA sequences was evaluated by Northern blot analysis. Albumin (ALB) gene expression was studied simultaneously with the same techniques. In 17-19-d-old fetuses all hepatocytes express simultaneously, for both genes, the mRNAs and the corresponding proteins. During the first postnatal weeks, at a time when the global number of AFP mRNA molecules decreases, all hepatocytes still contain cytoplasmic transcripts and protein. A zonal heterogeneity in the level of AFP gene expression develops around the first week, a higher number of gene products being detected in perivenous than in periportal hepatocytes. This heterogeneity persists until the fourth week when AFP mRNA sequences and protein are barely detectable. All hepatocytes express the ALB gene after birth, but at around the second week, a periportal intensification of the in situ hybridization signal and immunostaining becomes apparent. Our data indicate that co-expression of the AFP and ALB genes by all hepatocytes is a normal step in liver ontogeny; the diminution of AFP gene expression after birth is not the result of the disappearance of specialized cell clones; and zonal quantitative differences in the level of AFP and ALB gene expression are observed within the maturing liver lobule.

Albumins↗
PubMed1986

Influence of diets with different levels of protein and energy on liver albumin content in the rat.

The influence of protein ingestion on liver albumin synthesis and albumin content was investigated in rats fed protein as a meal (90% casein) given apart from the other dietary components provided ad libitum. In this condition, protein ingestion rapidly stimulates liver total protein synthesis. Separately fed rats were studied 6 and 20 h after the protein meal. Control rats fed mixed diets containing 13 or 80% casein were killed either during the absorptive (night) or postabsorptive (light) periods. The ratio of hepatic albumin synthesis to total protein synthesis remained fairly constant (12-15%) in all groups, indicating that albumin synthesis paralleled total protein synthesis. Liver albumin content measured in microsomes by immunonephelometry was significantly higher in separately fed rats killed 6 h postmeal than in those killed after 20 h. In rats fed 13% casein, the liver albumin content remained high regardless of the time of killing. In rats fed 80% casein, the albumin content was higher during the absorptive period than during the postabsorptive period. Immunoperoxidase staining of the hepatocyte organelles involved in albumin synthesis, especially the Golgi apparatus, was more intense for separately fed rats killed 6 h postmeal than for those killed after 20 h. Livers of rats fed 13% casein also exhibited a pattern indicative of high hepatocyte albumin content, whereas livers of rats fed 80% casein contained less. These results show that, in separate feeding, wide circadian variations of albumin synthesis run parallel to changes in liver albumin content.

Albumins↗
PubMed1986

Plasma-protein production by rat hepatoma cells in culture, their variants and revertants.

A series of subclones of the H4II line of the Reuber H35 rat hepatoma produce substantial amounts of three plasma proteins, transferrin, alpha 1-antitrypsin and fibrinogen. Immunocytochemical staining demonstrated that each of these proteins is synthesized by essentially every cell of these cell populations. Cells of dedifferentiated variant clones either cease to produce the proteins, or exhibit a substantial reduction that is accompanied by variability in the synthetic activity of individual cells of the population. As previously observed with regard to angiotensinogen production, the variant clones clearly divide into two categories: those that show only a reduction in synthesis are able to give rise to revertants, whereas the negative clones fail to do so. Revertant cells exhibit a dramatic restoration of the synthesis of plasma proteins, which in some cases, exceeds by severalfold the rates seen in the differentiated clones of origin. In addition, the revertant cells synthesize alpha-fetoprotein, a function that is not expressed by H4II cells or its daughter subclones. Immunocytochemical staining revealed that, with regard to several plasma proteins including albumin, fibrinogen and alpha-fetoprotein, the cell populations of revertant clones are very heterogeneous, for only a fraction of the cells synthesizes each protein. Hybrid cells resulting from several types of crosses, exhibited extinction of the plasma proteins, the exception being transferrin, whose production was maintained, but at a reduced level and in only a fraction of the cells. Taken together, our results show that the expression of albumin and transferrin can be dissociated from one to another, and from that of fibrinogen, alpha 1-antitrypsin and angiotensinogen.

Animals↗
PubMed1986

An ultrastructural study of rat hepatoma cells in culture, their variants and revertants.

We compared the ultrastructure of a well-differentiated rat hepatoma line (H4II) and its clonal progeny, including dedifferentiated variant cells, and revertants of the variants in which the spectrum of hepatocyte-specific functions is again expressed. The cells of the original differentiated lines and the revertants were very similar to one another. In addition, they exhibited some of the characteristics of fetal and neonatal hepatocytes. Variant cells which fail to express hepatocyte functions showed a wide range of morphological alterations accompanied by generalized disorganization. It is concluded that the loss of hepatocyte differentiation in the variants is not associated with a uniform morphological type, and that a wide range of ultrastructural phenotypes can be generated in the progeny of a single neoplastic but well-differentiated hepatocyte. Also, the expression of hepatocyte functions only occurs within a limited and organized morphological framework that includes features of young hepatocytes.

Animals↗
PubMed1986

Serial transmission of a human non A-non B hepatitis viral strain to HBV-protected chimpanzees: successive histological and ultrastructural studies.

A NANB agent of human origin was inoculated in HBV-immunized chimpanzees. Infection was proven in two animals and serially passed to two others. The absence of anti-HBc in serum and the absence of HBsAg and HbcAg in liver are arguments against the HBV nature of the transmitted infection. Moreover, the reproducible appearance of the NANBcAg/Ab system at each passage from man to chimpanzee and from chimpanzee to chimpanzee, a response not elicited in control animals, suggests that this reaction may be a specific immunologic marker for the strain. NANB infection was transmitted in all chimpanzees. Distinctive hepatic morphologic features were obtained in the liver biopsies of the human donor and the inoculated chimpanzees: eosinophilic alterations of hepatocytes and numerous inflammatory cells. Inflammation was more prominent than necrosis, appearing earlier and lasting longer, but was not topographically close to the eosinophilic changes. On electron microscopy, particles characteristic of NANB agent were observed in the cytoplasm of the hepatocytes. No particles were demonstrated in the nucleus of these cells.

Animals↗
PubMed1986

Amodiaquine-induced hepatitis. A report of seven cases.

Seven patients developed hepatitis after receiving amodiaquine for malaria prophylaxis for 4 to 15 weeks. Four patients had a minor form of hepatitis: jaundice was mild or absent, serum aminotransferase levels were moderately increased, and recovery was prompt. Three patients had a severe form: jaundice was intense, serum aminotransferase levels were markedly increased, jaundice persisted for 3 to 6 months, and liver tests were still abnormal 7 to 27 months after the onset of hepatitis. In two patients, serum aminotransferase levels increased promptly after readministration of the drug, which is consistent with an immunoallergic mechanism for amodiaquine-induced hepatitis.

Adult↗
PubMed1985

A modification of the hemolytic plaque test to investigate simultaneously secretion and morphological characteristics of individual cells.

A simple modification of the hemolytic plaque test is proposed which provides a morpho-functional approach to the study of secreting cells. The experimental procedure described here, an 'open system' with glass coverslips, involves the association of the reverse hemolytic plaque test performed in liquid medium with Feulgen's reaction used to reveal the nuclear characteristics of the secreting cells. A monolayer cell carpet, prepared with hepatocytes and sheep red blood cells coated with specific antibodies to transferrin, was attached to glass coverslips coated with 2 substrates, collagen and poly-L-lysine. Incubation was performed in a routine liquid culture medium. Under the conditions reported here to obtain an optimal attachment of the cells to the substrates, it was possible to stain hepatocytes after the formation of hemolytic plaques, whilst maintaining the monolayer cell structure intact. This technical modification should be of value in establishing correlations between secretory activity and cellular characteristics.

Animals↗
PubMed1985

All hepatocytes are involved in the expression of the albumin gene in the normal adult rat: a demonstration by in situ hybridization and immunoperoxidase techniques.

Immunoperoxidase techniques have yielded conflicting results concerning the percentage of hepatocytes engaged in albumin production in normal adult rats. In addition, the question of whether functional differences in the synthesis of plasma proteins exist within the hepatic lobule remains to be determined. To clarify these questions, we have searched for gene albumin transcripts by in situ hybridization, and for the corresponding protein by immunoperoxidase, on adjacent liver sections. We observed that all hepatocytes contain albumin transcripts as well as the albumin protein, without any detectable zonal variation within the liver lobule. Taken altogether, these results demonstrate that every hepatocyte, whatever its location in the hepatic lobule, is actively engaged in albumin gene expression.

Albumins↗