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Biomedical subjects

Y Deugnier

Publications and source records attributed to Y Deugnier.

At least 109 records · Page 6Linked to original sources
PubMed1989

Iron induction of ferritin synthesis and secretion in human hepatoma cell (Hep G2) cultures.

In order to determine if iron was able to stimulate specifically ferritin synthesis and secretion in transformed human hepatocytes in culture, human hepatoma cell (HepG2) cultures were submitted to increasing doses of ferric nitrilotriacetate. Iron uptake by the cells was demonstrated by incorporation of 59 Fe and the staining method of Perls. The following results were obtained: 1. iron incorporation within the hepatocytes increased as a function of culture time; 2. during the first 24 h of treatment, ferritin synthesis increased progressively, in parallel to the iron uptake; 3. a dose-dependent significant stimulation of ferritin synthesis and secretion were observed when the medium iron concentration increased from 5 to 20 mumol/l; 4. albumin, transthyretin and transferrin secretions were unaffected. These data demonstrated that, in our hepatocyte culture model, iron load increased the expression of ferritin in a highly specific manner.

Albumins↗
PubMed1989

Modulation of albumin secretion by ornithine alpha-ketoglutarate in adult rat hepatocyte cultures and a human hepatoma cell line (HepG2).

Cocultured adult rat hepatocytes and a human hepatoma cell line (HepG2) were maintained in an arginine-free medium with or without ornithine alpha-ketoglutarate. This drug increased greatly hepatocyte albumin secretion in both culture models. L-Ornithine was the component accounting for these effects since similar data were obtained by using this sole amino acid. Moreover, we observed that L-ornithine stimulation of albumin production was via polyamine synthesis. Since a correlated increase in albumin mRNA was observed, it may be postulated that ornithine alpha-ketoglutarate acts at a pretranslational level.

Albumins↗
PubMed1989

Effects of iron overload on transferrin secretion by cultured fetal rat hepatocytes.

Primary cultures of fetal rat hepatocytes were maintained in an arginine-free medium deprived of serum but supplemented with 0.03 mM L-ornithine and 10(-8) M dexamethasone. Ferric nitrilotriacetate was added to the culture medium in order to obtain iron concentrations ranging from 10 to 100 microM. After 24 h of treatment, iron was visualized inside the hepatocytes by the staining method of Perls and electron microscope study. The present data demonstrate that iron overload decreases transferrin secretion; this effect appears not to be specific, since albumin production is affected in a similar manner. This depressed transferrin secretion is not the consequence of hepatocyte death, as the phenomenon is confirmed when expressed per cell. Since the corresponding mRNA is unaffected, it may be postulated that iron overload decreases transferrin secretion at some post-transcriptional level.

Albumins↗
PubMed1988

Effect of ornithine on transferrin secretion of rat and human hepatocyte cultures.

Fetal rat or neonatal human hepatocytes and a human hepatoma cell line were cultured in an arginine-free medium, supplemented or not with L-ornithine. This amino-acid improved survival of hepatocytes and strongly enhanced their transferrin secretion. Moreover, this increase observed in transferrin production was well correlated with a higher corresponding mRNA level. Thus, it may be postulated that the mechanism involved in the increased transferrin secretion by L-ornithine is of pretranslational origin.

Animals↗
PubMed1988

Hepatic artery injection of I-131-labeled lipiodol. Part II. Preliminary results of therapeutic use in patients with hepatocellular carcinoma and liver metastases.

Internal radiation therapy with transarterial injection of iodine-131-labeled iodized oil (Lipiodol Ultra-Fluide [LUF]) was evaluated in 15 patients with hepatocellular carcinoma and eight with hepatic metastases. Five patients with hepatocellular carcinoma received more than one injection. Treatment tolerance was excellent, as assessed clinically and by means of liver function tests. An analgesic effect was noted in the two patients with painful hepatocellular carcinomas. Serum alpha 1-fetoprotein levels dropped rapidly in 11 of the 12 patients with elevated basal values. An average reduction in tumor size of 50% was observed in the nine cases followed up with computed tomography. After 5-12 months of follow-up, six of the 15 patients with hepatocellular carcinoma were alive. Two of them had undergone liver transplantation. Histologic examination of one of the livers, removed 3 months after a third injection, revealed microscopic features highly suggestive of radiation effect in LUF-containing areas. In the group with widespread hepatic metastases, no objective response was noted, except for an analgesic effect in three cases.

Adult↗
PubMed1988

[Biological markers in hepatocellular carcinoma].

Primary cancer of the liver, especially common in inter-tropical Africa and South-East Asia, still remains inaccessible to a really effective therapy, except for a rapid surgical excision. Improvement of its particularly poor prognosis requires therefore early screening based on reliable biological markers. Following alpha-feto-protein, various parameters have been proposed: enzyme, ferritin, desialylated serum protein, decarboxylated prothrombin... However, alpha-feto-protein remains, in practice, the reference diagnostic test, in spite of a moderate specificity below 500 ng/ml and the fact that it is frequently missing in early cancers. Its diagnostic score may be improved either by the use of monoclonal antibodies, or by determining the ratio of fucosylated form, or by concomitant use of other markers: alpha-L-fucosidase, decarboxy-prothrombin.

Antibodies, Monoclonal↗
PubMed1987

Chronic liver iron overload in the baboon by ferric nitrilotriacetate. Morphologic and functional changes with special reference to collagen synthesis enzymes.

Two baboons receiving intramuscular injections of ferric nitrilotriacetate over a two-year period were compared with two control baboons. The results indicate that in iron-overloaded animals: liver iron excess was major (maximal liver iron concentration values of 42 mumol/100 mg dry weight for both animals vs 1.3 +/- 0.2 (mean +/- SD) in controls) and chronic (for 15 months liver iron concentrations were higher than 15); iron deposition, although less abundant than in sinusoidal cells, was pronounced within parenchymal cells; serum transaminase activities were markedly increased; rare foci of perisinusoidal fibrosis were observed in areas of massive iron overload; and a dramatic decrease in hepatic 4-prolyl-hydroxylase activity was found, in contrast with unchanged glucosyltransferase and galactosyltransferase activities. In conclusion these findings suggest that, in our model, chronic liver iron overload: exerts a marked biochemical cytolytic effect; and does not produce significant hepatic fibrosis, possibly related to an inhibiting effect of ferric nitrilotriacetate complex on 4-prolyl-hydroxylase activity.

Animals↗
PubMed1987

[Iron overload of the liver and protein synthesis. Progress made through experimental models].

To understand the disturbances in protein synthesis observed during idiopathic hemochromatosis, various experimental models may be used. The aim of this research was to review the principal models employed and to demonstrate the value of hepatic tissue culture techniques in each. This method has already made it possible to explain several mechanisms involving the control of proteins in iron metabolism such as transferrin and ferritin. Tissue culture techniques of human hepatocytes should make it possible to elucidate the nature of the basic metabolic disorder in this disease responsible for the iron overload in the near future.

Animals↗
PubMed1986

[Surgical treatment of hepatoma on a cirrhotic liver].

From January 1, 1975 to July 1, 1984, 37 patients with a tentative diagnosis of hepatocarcinoma on cirrhosis were operated upon. There were 34 men and 3 women, aged from 32 to 82 years (mean: 60 years). The diagnosis of cirrhosis rested either on a history of liver failure associated with clinical and biochemical signs of hepatocellular dysfunction (4 cases), or on a positive liver biopsy (5 cases). In 20 cases the diagnosis was suspected on account of abnormal liver function tests, but in 8 patients it was revealed by macroscopic examination of the liver during surgery. Cirrhosis was attributed to chronic alcoholism in 25 cases, haemochromatosis in 11 cases and positive HBs antigen in 7 cases. The diagnosis of hepatocarcinoma, suggested by altered general condition or recent pain, rested on the finding of a tumoral image at scintigraphy (16 cases), ultrasonography (19 cases), computed tomography (7 cases), arteriography (17 cases) or laparoscopy (7 cases). In only 7/32 patients was the alpha-foetoprotein level higher than 500 ng/l. Surgery confirmed the diagnosis of hepatocarcinoma in every case but that of cirrhosis in only 14/37 cases; 10 patients had lesion of hepatic fibrosis and 1 had regenerative nodular hyperplasia. In 10 cases no accurate histological diagnosis could be made since the liver tissue sample had been taken too close to the tumour. The finding of normal liver tissue shows that one should not refrain from operating merely because the diagnosis of cirrhosis rests on clinical grounds. Since 1979, surgical treatment consists in an attempt to excise the tumour. Per-operative mortality is the same with excision surgery (21%) as with exploratory or palliative surgery (17%). Fourteen excisions were performed (i.e. aresectability rate of 38% for the series): 2 liver transplantations, 2 right hepatectomies, 2 left hepatectomies, 2 left lobectomies, 2 bisegmentectomies and 3 tumorectomies. The survival rate of 2 years was 27%, as opposed to 5% with exploratory or palliative surgery. Systematic monitoring of cirrhosis with ultrasonography should result in early diagnosis of hepatocarcinoma at a stage where limited hepatic excision is possible and the chances of surviving are highest.

Adult↗
PubMed1986

[Lipiodolized angiography in hepatocellular carcinomas. Contribution of iodine-131-labelled lipiodol].

Twelve patients with hepatocellular carcinoma and cirrhosis were investigated by Lipiodol injection into the hepatic artery. A CT scan was done 4-6 days later. Lipiodol was retained by hepatic tumors in each case. This method emphasized the extension of the carcinoma and allowed to discover daughter tumors. I131-lipiodol was also injected in 4 of the 12 patients and then its biodistribution was evaluated. At the 6th hour after injection, I131-lipiodol was detected by scintigraphy over the liver (74-91 percent) and over the lungs (9-16 percent) only. The tumor to normal liver pixel count ratio was about 5. These results indicate that there is a preferential arterial blood flow towards the hepatic tumors, and that we can consider a therapeutic use of I131-Lipiodol in hepatocellular-carcinoma.

Adult↗
PubMed1985

Diagnostic value of erythrocyte-free polyamines and histaminemia in malignant hepatic tumors and in liver cirrhosis.

The present study tries to evaluate the diagnosit value in malignant hepatic tumors of polyamines, of which the relationship with cellular kinetics is known, and histamine, of which catabolism follows a similar pathway. One hundred and fifty six patients were studied: 53 with malignant liver tumors (27 primary, 26 metastatic) and 103 with non-tumoral liver diseases of which 65 were cirrhotic and 38 non-cirrhotic. Erythrocyte polyamines (spermidine and spermine) and histamine levels were assayed. The results indicate the following. 1. Polyamine levels were significantly increased (a) in cirrhotic patients, not only when compared with controls (p less than 10(-8)), but also when compared with the non-cirrhotic patients (p less than 10(-7)); (b) in primary malignant hepatic tumors (p less than 10(-3)). 2. Histamine was significantly increased (a) in the non-tumoral liver diseases (p less than 10(-4)), but with no difference between cirrhotic and non-cirrhotic patients; (b) in the secondary malignant tumor patients, histamine levels were lower than in primary tumor patients (p less than 0.04). 3. There was no correlation, in all groups studied, between polyamine and histamine levels. These results suggest the following practical implications. 1. For non-tumor liver diseases, appreciably increased polyamine levels may represent a further argument favoring a cirrhotic condition. 2. In diagnosing hepatic scintigraphic defects, increased polyamine levels would suggest a primary malignant hepatic tumor; low histamine levels are more in favor of a secondary malignant hepatic process.

Adult↗
PubMed1985

Iron overload of the liver in the baboon. An ultrastructural study.

Liver biopsies from 4 baboons taken during 15 months of iron-polymaltose injections, were compared with specimens from 2 controls. A morphometric method was used to assess ferritin concentration in various cells. Initially, ferritin and siderosomes were conspicuous in reticuloendothelial cells but rare in hepatocytes. Unusual findings included intranuclear ferritin and coalesced ferritin within bile canaliculi. With advancing overload, ferritin and hemosiderin increased not only in sinusoidal cells, but also in hepatocytes, with concomitant elevation of transaminases. The hepatocytes now showed evidence of damage and excessive collagen was present mainly around portal spaces. A year after cessation of iron injections, hepatocyte ultrastructure was near normal while sinusoidal cells were still heavily overloaded. The baboon appeared to be a useful model for the study of iron overload. Although in this study most of the damage was reversible, it is suspected that more prolonged overload, a different route of administration or other, more toxic iron compounds, may lead to cirrhosis similar to that of the iron-loading anemias.

Animals↗
PubMed1985

Is the HLA-linked haemochromatosis allele implicated in idiopathic refractory sideroblastic anaemia?

In order to assess the previously reported association of HLA-linked idiopathic haemochromatosis with idiopathic refractory sideroblastic anaemia (IRSA), the prevalence of HLA-A3 antigen in a group of 22 patients with IRSA was compared to that observed in healthy controls and in patients with homozygous idiopathic haemochromatosis and to that calculated for a population heterozygous for idiopathic haemochromatosis. The prevalence of A3 in patients with IRSA (0.23) was quite similar to that observed in controls (0.29) and significantly different from that observed in homozygous (0.73; P less than 10(-5] and heterozygous (0.57; P less than 10(-3] haemochromatosis. Serum iron, transferrin saturation, serum ferritin and liver iron concentration showed no difference in IRSA patients with or without A3. It is concluded that there is neither systematic association between the haemochromatosis allele and IRSA nor systematic implication of such an allele in the development of iron overload observed in IRSA.

Aged↗