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G Feldmann

Publications and source records attributed to G Feldmann.

At least 163 records · Page 9Linked to original sources
PubMed1990

Adenylate cyclase and carbonic anhydrase in the semicircular canal epithelium of the frog Rana esculenta. An ultrastructural cytochemical localization.

Because the secretion of endolymph has been localized in the ampullar part of the frog semicircular canal, we attempted to determine by cytochemical methods the ultrastructural localization of two enzymes that are assumed to play a role in endolymph secretion: carbonic anhydrase and adenylate cyclase. Functionally, the epithelium of the frog semicircular canal can be schematically divided into three areas: sensory (crista ampullaris), secretory (dark cells), and non-sensory and nonsecretory (transitional and undifferentiated cells) areas. Carbonic anhydrase activity was widely distributed in dark cells. Dark cell labeling disappeared in the presence of acetazolamide. The other cells of the canal did not show any carbonic anhydrase labeling except for the supporting cells of the sensory cells. Adenylate cyclase activity was found on the basolateral and apical membranes of dark cells, and on the apical membrane of sensory cells; weak labeling was also observed in the other epithelial cells. In the apical membrane of the dark cells, adenylate cyclase labeling was dependent on the presence of vasotocin, the frog antidiuretic hormone. The dark cells of the frog semicircular canal thus possess the enzyme equipment needed for the secretion of endolymph and its possible hormonal regulation.

Adenylyl Cyclases↗
PubMed1990

Bile canalicular alterations in hepatocyte nodules induced by 3'-methyl-4-dimethylaminoazobenzene in the rat: morphological clues on their pathogenesis and relevance to the neoplastic process.

One characteristic change of hepatocyte plasma membrane in chemically induced nodules of rat liver is the spreading over on the whole cell surface of proteins normally associated with the canalicular domain. However, these proteins may present comparable altered patterns of membrane distribution in non-neoplastic situations, e.g. in cholestatic states. Consequently, the significance of an abnormal membrane distribution of canalicular proteins in hepatocyte nodules and its possible relevance to the neoplastic process remain to be clarified. We have therefore performed an ultrastructural study of bile canalicular alterations in the hepatocyte nodules induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), in an attempt to gain some insight on their pathogenesis. We actually observed frequent bile canalicular changes in hepatocyte nodules from 10 to 16 weeks after the beginning of 3'-Me-DAB administration. These changes correlated with the rearrangements in hepatocyte architecture occurring at this stage of the neoplastic process, corresponding to the so-called pseudo-acinar structures and disorganized plates. In pseudo-acinar structures, hepatocytes were arranged in a tubular manner around dilated bile canaliculi. In this situation, bile canaliculi have lost many of their normal features and closely resemble ductular lumina. In disorganized plates, hepatocyte plates were thickened and irregularly branched. In this situation, bile canaliculi presented striking deviations from the normal, including: (i) dilatation and distortion, (ii) lesions of canalicular membrane (loss of microvilli, formation of blebs) and (iii) alterations in the pericanalicular cytoskeletal network. Most of these morphological abnormalities closely resembled those found in cholestatic states. Two pathogenetic mechanisms may be postulated to explain the cholestatic-like effect of 3'-Me-DAB: (i) a direct cellular injury caused by the carcinogen or (ii) an indirect consequence of the tissular rearrangements characteristic of disorganized plates. Our morphological results suggest that the phenotypic alterations of bile canaliculi induced by 3'-Me-DAB are not specific for the neoplastic process. They are likely to correspond to an impairment in the biogenesis of the canalicular membrane and/or in the maintenance of its integrity.

Animals↗
PubMed1990

Acute hepatitis after tetrahydroaminoacridine administration for Alzheimer's disease.

Tetrahydroaminoacridine administration has been proposed as a treatment for Alzheimer's disease. Although recent studies have shown that tetrahydroaminoacridine administration can be associated with mild or moderate liver dysfunction, to our knowledge, no case of symptomatic hepatitis with severe liver lesions has heretofore been reported. We describe a patient who developed jaundice after receiving tetrahydroaminoacridine for three weeks. Histologic examination showed extensive hepatocellular necrosis. Tetrahydroaminoacridine withdrawal was followed by the disappearance of jaundice within a few days and complete recovery within 5 weeks. This case shows that tetrahydroaminoacridine administration can induce marked liver cell necrosis resulting in symptomatic acute hepatitis.

Acute Disease↗
PubMed1990

In situ hybridization: application to the study of gene expression during experimental hepatocarcinogenesis and human hepatocellular carcinoma.

The possibility of detecting specific mRNA directly within tumor cells offered by the in situ hybridization (ISH) technique has provided a new dimension to the study of experimental and human hepatocarcinogenesis. The combination of ISH and immunocytochemical techniques on the same or adjacent tissue sections provides a more complete picture of the various changes in gene expression. ISH may also detect posttranscriptional abnormalities of gene expression at the cellular level, such as expression of mRNA with no protein translation, or translation with decreased efficiency. Undoubtedly, the development of the ISH technique will open a new area for the understanding of the complex molecular events leading to cancer.

Albumins↗
PubMed1990

Detection of a biliary cell membrane glycoprotein in the serum of cholangiocarcinoma-bearing rats. Possible relevance to the membrane proteins used as serum tumor markers in humans.

Certain markers used in the diagnosis and monitoring of human adenocarcinomas, such as carcinoembryonic antigen are membrane glycoproteins normally absent from the serum. How those proteins may reach the blood after the neoplastic transformation remains debated. In this work, we show that cholangiocarcinoma induced by 3'-methyl-4-dimethylaminoazobenzene in the rat provides some insight into the mechanisms implicated in this process. We observed that the extracellular matrix of all cholangiocarcinomas tested contained large amounts of a glycoprotein identified by a monoclonal antibody termed B10, and previously characterized as an integral membrane protein normally restricted to the apical domain of epithelial cell plasma membrane. The extracellular deposition of the B10-binding glycoprotein in cholangiocarcinomas was associated with the appearance of detectable levels of the protein in the serum, and an abnormal membrane expression of the protein, which was detected on both apical and basal plasma membrane domains of neoplastic biliary cells. We postulate that neoplastic transformation of biliary cells leads to an inappropriate membrane expression of the B10-binding protein, which in turn, results in the extracellular release of the protein and in its diffusion into the blood. The characteristic desmoplastic stroma of cholangiocarcinoma offers the opportunity to easily visualize the release process. A comparable mechanism is likely to explain how certain membrane glycoproteins used as serum markers in human malignancy may reach the blood.

Adenoma, Bile Duct↗
PubMed1989

Heterogeneous lobular distribution of hepatocytes expressing acute-phase genes during the acute inflammatory reaction.

Functional heterogeneity in the lobule with regard to plasma protein synthesis is still debated. Therefore, we have localized in liver sections from normal rats and from rats with turpentine-induced AIR the mRNA and protein products of three genes with different alterations in their hepatic expression during an AIR: alpha 2M and alpha 1PI, two positively reacting acute-phase genes, and alpha 1I3, a negative acute-phase reactant. In normal liver, all hepatocytes expressed alpha 2M and alpha 1I3 mRNA, but a preferential expression of alpha 2M and alpha 1I3 mRNA and protein in the PP and ML zones was observed. During an AIR, the level of alpha 2M mRNA increased fourfold in the cytoplasm of PP and ML hepatocytes, while the level of cytoplasmic alpha 1I3 mRNA was decreased about fourfold in the same zones, with parallel variations in the expression of the corresponding proteins. In contrast, no significant modulation of the RNA and protein concentrations of both genes was detected in PV areas. alpha 1PI mRNA was expressed at the same levels in the three lobular zones in normal liver, but staining for the alpha 1PI protein was more intense in the PV zones. During the acute-phase response alpha 1PI mRNA levels were increased twofold in all three lobular zones, and alpha 1PI staining became homogeneous within the lobule. These results demonstrate that the location of a hepatocyte with the liver lobule can influence the expression of the three genes under study both at pre- and post-translational levels, in basal conditions, as well as during modulation of their expression during the inflammatory reaction.

Acute Disease↗
PubMed1989

Cellular expression of alpha-fetoprotein gene and its relation to albumin gene expression during rat azo-dye hepatocarcinogenesis.

During hepatocarcinogenesis, alpha-fetoprotein (AFP) synthesis may be dramatically increased while albumin synthesis is frequently decreased. Therefore, a reciprocal modulation between both gene expressions has been hypothesized. In this work, we combined in situ hybridization and immunoperoxidase on parallel liver tissue sections in order to analyze at the cellular level, AFP gene expression and its relation to ALB gene expression in both early and neoplastic lesions induced by 3MeDAB in the rat. In early lesions, cell populations were heterogenous as regards AFP expression. High levels of AFP transcripts were detected both in oval type cells and in a subset of basophilic hepatocytes within preneoplastic lesions. In these two highly AFP-expressing cell populations, significant levels of ALB transcripts were concomitantly detected. In the majority of altered hepatocytes, no AFP expression was detected while the level of ALB expression was decreased. In neoplastic lesions, AFP expression was strikingly heterogenous and independent from the degree of morphological differentiation. No evidence of reciprocal modulation with ALB gene expression could be assessed. In both preneoplastic and neoplastic lesions, a few altered hepatocytes displayed significant levels of AFP transcripts while no corresponding protein could be detected; such a discrepancy was not observed for ALB. This work shows that during 3MeDAB hepatocarcinogenesis, AFP gene activation occurs in heterogenous cell populations and according to different cellular patterns. Our observations lend no support to the hypothesis of a reciprocal modulation between AFP and ALB gene expressions during rat azo-dye hepatocarcinogenesis.

Albumins↗
PubMed1989

Further cellular investigation of the human hepatoblastoma-derived cell line HepG2: morphology and immunocytochemical studies of hepatic-secreted proteins.

The hepatoblastoma cell line HepG2 has been a matter of many investigations; most of them include biochemical studies of lipoprotein and other hepatic protein metabolism. However, the accurate cellular features of these cells have not been emphasized. We studied the cellular histologic, histochemical, and ultrastructural characteristics of this cell line. In addition, we investigated by immunoenzymatic methods the cellular biosynthesis of several proteins: apolipoproteins-AI, -B, -D, and -E, albumin, alpha-fetoprotein, transferrin, alpha-1-antitrypsin, C-reactive protein, fibronectin, and collagens I, III and IV. The rates of accumulation, in the medium of HepG2 cells, of albumin, alpha-1-antitrypsin, transferrin, and alpha-fetoprotein were 13.2 +/- 1.9; 4.9 +/- 1.5; 3.2 +/- 0.4; and 10.7 +/- 1.7 micrograms/10(6) cells/24 h, respectively. Our results show that HepG2 cells exhibited most cellular features of normal human hepatocytes. Bile canaliculi as well as Golgi apparatus complexes were particularly developed. Except for the C-reactive protein, HepG2 cells have all retained the ability to synthesize hepatic proteins but with some variable intensity from cell to cell. This hepatoblastoma cell line seems to represent a useful tool in the understanding of hepatic protein biosynthesis, particularly for the investigation on the secretory pathway of plasma proteins.

Albumins↗
PubMed1989

Epithelioid hemangioendothelioma of the liver: an ultrastructural study.

Epithelioid hemangioendotheliomas are uncommon vascular tumors, mainly observed in lung and soft tissues. Liver involvement is infrequent and, in contrast to the extrahepatic localizations of the tumor, has not been subjected to detailed ultrastructural analysis. This prompted us to report the results of the ultrastructural study of three cases of epithelioid hemangioendothelioma of the liver. Neoplastic proliferation was heterogeneous. Most of neoplastic cells presented features suggestive of endothelial differentiation, including presence of Weibel-Palade bodies and evidence of vasoformative properties demonstrated by formation of both intra- and extracellular vascular channels resembling the normal structures successively observed during embryogenesis and tissue regeneration. A minor cell population, unreported so far, exhibited ultrastructural characters resembling those of pericytes and presented organoid relationship to neoplastic endothelial cells. Tumor spreading along sinusoids induced pseudopeliotic dilatations and led to a progressive disruption of normal liver architecture. In conclusion, the three cases of hepatic epithelioid hemangioendothelioma examined in this work assume many organoid features mimicking the successive steps of normal angioformation and indicative of a high degree of morphological differentiation.

Adult↗
PubMed1989

Expression of rat hepatocyte plasma membrane antigens in hybrid clones: assignment of genes coding for two antigens of the basolateral domain to chromosomes 11 and 13.

Expression of three rat hepatocyte plasma membrane antigens defined by monoclonal antibodies (mAbs) was examined by immunofluorescence in mouse hepatoma x rat hepatocyte hybrid clones segregating rat chromosomes. The antigen defined by mAb B1, a marker of the lateral domain of the hepatocyte plasma membrane in vivo, was expressed in hybrids retaining the rat chromosome 11. The antigen defined by mAb A39, mainly located on the sinusoidal (basal) domain of the plasma membrane in vivo, was expressed when chromosome 13 was present. The genes coding for these two antigens were thus assigned to chromosomes 11 and 13, respectively. The antigen defined by mAb B10, exclusively located on the canalicular (apical) domain of the plasma membrane in vivo, was not expressed in most hybrid clones, and the chromosome location of the gene could not be determined.

Animals↗
PubMed1989

[In situ hybridization: principles and applications].

In situ hybridization is a molecular biological technique recently introduced in histology. Its principle consists of forming stable nucleic hybrids in tissues or cells. In this review, the main steps of the technique are discussed in regard to the preparation of probes and their labelling, the fixation of tissues and cells and their permeabilization in order to facilitate the penetration of labelled probes. Conditions of hybridization and requisite control reactions are also analysed. Quantification possible when radioactive probes are used is detailed. The three current applications of in situ hybridization, the localization of a gene on a chromosome, the demonstration of viral genomes in cells and the investigation of messenger RNAs coding for a determined protein, are illustrated with specific examples.

Animals↗
PubMed1989

[Idiopathic portal hypertension associated with connective tissue disease similar to systemic lupus erythematosus].

A case of idiopathic portal hypertension associated with connective disease resembling systemic lupus erythematosus is described. The patient was a 50-year-old woman with splenomegaly, ascites, esophageal varices, and pancytopenia, but without extrahepatic portal obstruction or cirrhosis of the liver. Electron microscopy of the liver showed perisinusoidal fibrosis. High titers of autoantibodies against proliferating cell nuclear antigen (PCNA) were found in the sera as well as in ascites; anti-DNA antibodies appeared after anti-PCNA antibodies and remained thereafter at a moderate titer. The possibility of an immunological process in the pathogenesis of idiopathic portal hypertension is discussed.

Antibodies, Antinuclear↗
PubMed1989

[Hepatitis probably caused by exifone (Adlone)].

Exifone, a drug recently proposed for the treatment of cognitive deficiencies of old age, has been marketed in France beginning in April 1988. This report concerns 2 patients who developed jaundice after taking this drug for 2 and 5 months, respectively. Serum aminotransferase was markedly increased. There was no hepatic failure. In both cases, histologic examination of a liver sample showed centrilobular hepatocyte necrosis and cholestasis. Necrotic cells were infiltrated with numerous red blood cells and scarce inflammatory cells. These lesions were associated with alterations of the walls of centrilobular veins. Discontinuation of exifone was followed by the prompt disappearance of jaundice. Complete recovery occurred within 6 and 12 weeks, respectively.

Aged↗
PubMed1989

Comparative effects of halothane and isoflurane anesthesia on the ultrastructure of human hepatic cells.

The effects of halothane and isoflurane on the ultrastructure of the liver cells in adult patients with normal liver-function tests were compared. After induction of anesthesia with thiopental, fentanyl, and pancuronium, 18 patients were randomly divided into three groups of six each. Anesthesia was maintained with droperidol (droperidol group), with halothane (1.7 MAC, halothane group), or with isoflurane (1.7 MAC, isoflurane group). During the surgical procedure, 1 hr after the induction, a liver biopsy was performed in each patient and processed for light and electron microscopy. All biopsies were normal on light microscopy. On electron microscopy, no mitochondrial abnormalities were found. In all three groups, irregular nuclear membranes, dilation of the rough endoplasmic reticulum, and vesiculation of the smooth endoplasmic reticulum were seen, without any significant differences between the groups. There were significantly more lysosomes in the hepatocytes of patients receiving halothane than in the hepatocytes of patients receiving isoflurane or droperidol. This study shows that halothane can induce ultrastructure abnormalities very early after the beginning of its administration while, under the same conditions, isoflurane does not.

Adult↗
PubMed1988

Analysis of hepatocyte plasma membrane polarity during rat azo dye hepatocarcinogenesis using monoclonal antibodies directed against domain-associated antigens.

While carcinogenesis is known to induce various alterations in epithelial cell polarity, little information is available about the fate of plasma membrane polarity during the neoplastic process. Using three monoclonal antibody-defined antigens as markers of the three plasma membrane domains of rat hepatocytes, the sinusoidal, the lateral, and the canalicular, we demonstrated by immunohistochemical techniques that changes in hepatocyte plasma membrane polarity occur at every stage of 3'-methyldimethylaminoazobenzene-induced hepatocarcinogenesis. At the preneoplastic stage, the division of hepatocyte plasma membrane into three distinct domains was retained despite rearrangements in hepatocytic architecture, characterized by the disorganization of hepatocytic plates and the formation of pseudoacinar structures. The most striking change was the distribution of the canalicular-associated antigen over the entire plasma membrane in disorganized plates. At the neoplastic stage, changes in plasma membrane polarity depended on the degree of morphological differentiation of neoplastic cells. Poorly differentiated cells inconstantly expressed the monoclonal antibody-defined antigens and showed no evidence of plasma membrane polarization. Differentiated cells constantly expressed the three antigens, and their plasma membrane was divided into antigenically distinct domains. The changes in hepatocyte plasma membrane polarity demonstrated in situ during 3'-methyldimethylaminoazobenzene hepatocarcinogenesis may therefore be compared with situations known to occur in vitro, in cultured epithelial cells presenting varying degrees of polarization. Our observations suggest that these alterations are of relevance to the in vivo biology of cancer.

Animals↗