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Biomedical subjects

G Feldmann

Publications and source records attributed to G Feldmann.

At least 217 records · Page 12Linked to original sources

Myeloid metaplasia, perisinusoidal fibrosis, and nodular regenerative hyperplasia of the liver.

We describe two patients with myeloid metaplasia in whom portal hypertension resulted, not from infiltration of the liver sinusoids by myeloid cells, but from perisinusoidal fibrosis and nodular regenerative hyperplasia of the liver. We hypothesize that myeloid metaplasia induced the development of perisinusoidal fibrosis, which resulted in heterogeneous hepatic tissue blood perfusion, with atrophy of the liver cells in the underperfused areas and nodular regenerative hyperplasia in the normally perfused areas.

Aged↗

Ammonium chloride, methylamine and chloroquine reversibly inhibit antibody secretion by plasma cells.

The effects of the lysosomotropic weak bases, NH4Cl, methylamine and chloroquine, on the secretory process of antibody-synthesizing cells were studied. Popliteal lymph node cells taken from rats immunized against horseradish peroxidase (HRP) were incubated with the lysosomotropic agents. The rate of secretion of anti-HRP antibodies was measured using an indirect enzyme-linked immunosorbent assay. These agents induced an inhibition of antibody release within 5 min, and for all four concentrations tested, maximal inhibition was reached after 15 min. A 50% inhibition was obtained with 20 mM NH4Cl, 21.7 mM methylamine and 8.8 X 10(-4) M chloroquine. This effect was rapidly and entirely reversible, regardless of the weak base used, and it increased as the pH of the extracellular media was raised. Under these conditions, intracellular ATP contents remained normal, and protein synthesis did not undergo marked changes except with chloroquine. Inhibition of secretion was accompanied by an intracellular accumulation of antibodies which was equal to the degree of inhibition of antibody release. Immunocytochemical studies of the weak base-treated cells performed by light and electron microscopy showed that this accumulation probably occurred within certain dilated Golgi saccules. In addition, reduced incorporation of fucose into immunoglobulins as well as partial inhibition of the secretion of fucosylated immunoglobulins were observed in the presence of weak bases. These results are consistent with the hypothesis that weak bases inhibit antibody secretion by acting within saccules of the Golgi apparatus. These saccules could maintain an acidic pH important for the migration and/or sorting of immunoglobulins.

Adenosine Triphosphate↗

Liver perisinusoidal fibrosis in BB rats with or without overt diabetes.

Perisinusoidal fibrosis is a vascular lesion observed in the liver of type I diabetic patients. To investigate whether this liver lesion is secondary to hyperglycemia or whether it represents a separate collagen vascular disorder, the authors studied the structure of liver sinusoids in genetically susceptible BB rats in which a spontaneous diabetes develops similar to human type I diabetes. Seven diabetic insulin-treated BB rats, 7 nondiabetic BB rats, and 6 control non-BB rats were studied. Histologic abnormalities of the collagen network were detected on trichrome-stained sections. Perisinusoidal collagen fibers were quantified ultrastructurally by the point-counting method. All control non-BB rats had normal livers; 86% of the diabetic as well as 71% of the nondiabetic BB rats displayed localized sinusoidal thickening corresponding ultrastructurally to perisinusoidal fibrosis; in these abnormal rats the percentage of collagen fibers per sinusoid unit was significantly higher than that in controls. Fibrous septa (2 diabetic and 5 nondiabetic BB rats) and liver nodulation (3 diabetic and 1 nondiabetic BB rats) were also observed. Perisinusoidal fibrosis is a frequent liver vascular abnormality in a strain of rats genetically predisposed to the development of type I diabetes. The lesion is independent of the presence of diabetes. These observations suggest that liver perisinusoidal fibrosis in patients with type I diabetes might be linked to a genetic abnormality rather than to hyperglycemia per se.

Animals↗

Characterization of rat hepatocyte plasma membrane domains by monoclonal antibodies.

The hepatocyte plasma membrane consists of three morphologically and functionally distinct domains, the sinusoidal, the lateral and the canalicular. To study the distribution of antigenic determinants among these domains, we prepared monoclonal antibodies by immunizing mice with a crude, plasma membrane-enriched liver fraction. Four monoclonal antibodies were obtained that recognized various parts of the rat hepatocyte plasma membrane when tested by indirect immunofluorescence and immunoperoxidase assay performed on formaldehyde-fixed liver tissue. Each antibody gave a different staining pattern when analyzed by light and electron microscopy. A59 exclusively labelled the part of the sinusoidal membrane facing the sinusoids. A39 mainly labelled the sinusoidal membrane. B1 mainly labelled the lateral membrane, while the labelling by B10 was almost completely limited to the canalicular membrane. Immunoblotting showed that the antibody B1 recognized an antigen of approximately 100 kilodaltons and that B10 recognized an antigen of approximately 125 to 130 kilodaltons. These antibodies allow us to distinguish the three domains of the hepatocyte plasma membrane.

Animals↗

Acetylsalicylic acid compared with acetylsalicylic acid plus codeine as postoperative analgesics after removal of impacted mandibular third molars.

In a multicenter, double blind clinical trial a combination of acetylsalicylic acid 500 mg + codeine phosphate 30 mg has been compared with acetylsalicylic acid 500 mg as postoperative analgesics in patients with pain after surgical removal of impacted mandibular third molars. Evaluation of the results from 129 patients showed that the combination of acetylsalicylic acid and codeine provided better pain relief and also the number of tablets used was smaller and the time intervals between repeated doses were longer than with acetylsalicylic acid only. Adverse effects were few and similar for both drugs. It may be concluded that the combination of 500 mg acetylsalicylic acid and 30 mg codeine phosphate provides a useful analgesic for more severe pain conditions in oral surgery.

Adolescent↗

[An unusual case of clear-cell chondrosarcoma with intrasynovial tumoral localization].

A case of a clear-celled chondrosarcoma of the femoral condyle extending into the knee joint is reported. At operation, many nodules looking like benign osteochondromata were found. They were found to be due to dissemination of the chondrosarcoma. An electron-microscopic study showed that the matrix was different in the osseous tumour from that in the synovial nodules. The result was satisfactory five years after resection followed by arthrodesis.

Adult↗

Cytoskeleton ultrastructure of podocytes and glomerular endothelial cells in man and in the rat.

The ultrastructural organization of the cytoskeleton of normal podocytes and glomerular endothelial cells was studied in man (adults and children) and in adult Sprague-Dawley rats. In podocytes of both species, cytoplasmic microtubules (MT) were observed in the cell body close to the Golgi apparatus and along the main axis of the major processes where they formed bundles. A network of intermediate filaments (IF) was observed in the cell body and in the major processes where they sometimes formed bundles parallel to MT, especially in man. Numerous clustered microfilaments (MF) were noticed in the foot processes close to the plasma membrane. In glomerular endothelial cells from both species, networks of MT and IF were observed in the cell body, whereas MF surrounded the endothelial fenestrations. The high degree of organization of the cytoskeleton suggests that it may play an important role in several functions of both cell types.

Animals↗

Peliosis-like ultrastructural changes of the hepatic sinusoids in human chronic hypervitaminosis A: report of three cases.

In addition to hypertrophy of Ito cells and perisinusoidal fibrosis, previously unrecognized ultrastructural abnormalities of the hepatic sinusoids were observed in three patients with chronic hypervitaminosis A: 1) large areas of communication between the sinusoidal lumina and the perisinusoidal spaces, allowing extravasation of blood cells; 2) marked dilation of the perisinusoidal spaces; and 3) swelling and clarification of endothelial cells. Most of these changes, along with some other sinusoidal barrier alterations previously reported in chronic hypervitaminosis A (i.e., bleb formation on the sinusoidal membrane of the hepatocytes and the presence of multiple cellular layers lining the sinusoids), are strikingly similar to those observed in peliosis hepatis. The present findings suggest that sinusoidal barrier abnormalities might constitute a major event in the pathophysiology of vitamin A-induced liver injury as well as of peliosis hepatis.

Adult↗

Recurrent jaundice caused by recurrent hyperemesis gravidarum.

The existence of jaundice induced by hyperemesis gravidarum is controversial. We report the case of a woman who suffered from three episodes of jaundice during the first trimester of three consecutive pregnancies, a few days after the onset of hyperemesis gravidarum. Jaundice was caused by conjugated hyperbilirubinaemia. Serum alanine aminotransferase activity was increased and scarce necrotic hepatocytes were shown on light and electron microscopic examinations. Cessation of vomiting was rapidly followed by complete recovery. This observation supports the view that severe vomiting can cause jaundice in pregnant women.

Adult↗

Study of biochemical behavior of some exported and nonexported hepatic proteins during an acute inflammatory reaction in the rat.

Haptoglobin, albumin, glucose-6-phosphatase, p-nitrophenol uridine diphosphate (UDP)-glucuronosyltransferase and cytochrome P-450 were measured in liver microsomes from normal rats and from rats undergoing an acute inflammatory reaction (AIR) induced either by subcutaneous administration of turpentine or by intrapleural injection of calcium pyrophosphate. 24 h after the beginning of the AIR induced by subcutaneous administration of turpentine, haptoglobin and albumin, two exported proteins, had risen to a peak (+313%), and dropped considerably (-52%) whereas nonexported protein levels did not change except for cytochrome P-450, which diminished (-38%). In the same way, intrapleural injection of calcium pyrophosphate was followed after 24 h by significant but smaller variations in haptoglobin (+60%) and cytochrome P-450 (-20%) concentrations. Albumin levels, glucose-6-phosphatase and p-nitrophenol UDP-glucuronosyltransferase activities were unchanged in this experimental model. The drop in cytochrome P-450 under all these conditions and also the diminution of albumin in the first model suggest that all the proteins produced by liver cells might not be synthesized in equal amounts. The decrease in cytochrome P-450 could interfere in hepatic drug metabolism during an AIR.

Acute Disease↗

In situ ultrastructural detection and quantitation of liver mononuclear phagocytes in contact with hepatocytes in chronic type B hepatitis.

An ultrastructural cytochemical method for detection of endogenous peroxidase was used to quantify the mononuclear phagocytes present in areas of tissue injury, i.e., in membrane contacts with hepatocytes, in liver biopsies from 12 patients with chronic type B hepatitis; 10 of them exhibited stable disease activity of various degrees of severity, and the other two displayed acutely exacerbated disease activity. Results were compared with those for three patients with acute type B hepatitis. The total percentage of mononuclear phagocytes was higher in patients with chronic hepatitis with stable high disease activity than in patients with stable low disease activity (31.3 +/- 7.4 versus 15.6 +/- 4.7%, p less than 0.01). Furthermore, in the former group of patients, recently recruited macrophages were significantly more frequent than in patients with low disease activity (11.6 +/- 4.0 versus 3.5 +/- 3.6%, p less than 0.01), and macrophages often displayed a markedly hypertrophied cytoplasm with numerous phagolysosomes, suggestive of an activated state. On the other hand, no significant differences in the percentage of the other leukocytes in contact with hepatocytes (lymphocytes, plasmocytes, and polymorphonuclear leukocytes) were noted between patients with high and low disease activity. In the three biopsies obtained from two patients with chronic hepatitis with acute exacerbation of disease activity, the profile of the leukocytes in contact with hepatocytes strikingly resembled the one observed in the three patients with acute type B hepatitis. In both instances, mononuclear phagocytes were rare, and a higher proportion of lymphocytes was observed than in patients with stable chronic liver disease activity. These results suggest that the mechanisms of hepatocyte necrosis in chronic type B hepatitis may differ from that in acute hepatitis due to this virus. Although lymphocyte-mediated mechanisms are likely to be predominant during acute episodes of hepatocyte necrosis, mechanisms mediated by mononuclear phagocytes might play a significant role in the low grade of hepatocyte necrosis characteristic of stable chronic type B hepatitis.

Acute Disease↗

Ultrastructural lesions of the liver in human peliosis. A report of 12 cases.

Ultrastructural lesions of the liver were studied in 12 patients with peliosis hepatis. This vascular lesion consisted of cavities filled with red blood cells and sometimes lined with an endothelial barrier; the cavities were due to cystic dilatation of the space of Disse and/or sinusoidal lumen. The passage of red blood cells through the endothelial barrier was occasionally demonstrated. Other striking alterations included the presence of numerous blebs on the sinusoidal membrane of the hepatocytes and the existence of multiple cellular layers lining the sinusoids. Perisinusoidal fibrosis appeared on follow-up biopsies in 3 patients. There was no major abnormality of the hepatocytes or of the hepatic venules. These findings suggest that alterations of the sinusoidal barrier might constitute the primary event in peliosis, although secondary changes to increased pressure and hypoxia within the lobules cannot be excluded.

Adolescent↗

Comparison between conjugate and non-conjugate immunoperoxidase procedures with special reference to intracellular penetration. Application to albumin localization in rat hepatocytes.

Three immunoenzymatic methods, peroxidase-labelled antibody, peroxidase-labelled immunoglobulin Fab fragment and unlabelled antibody peroxidase-antiperoxidase methods were compared for albumin localization in rat hepatocytes. On liver cryostat sections observed with light microscopy, the peroxidase-antiperoxidase method was the most sensitive, since albumin was detectable at high dilutions of the primary layer antiserum. Penetration of the conjugated and non-conjugated antibodies into liver tissue was evaluated by electron microscope examination of ultrathin transverse sections cut from cryostat sections. The best penetration and staining of hepatocellular organelles were obtained with peroxidase-labelled Fab fragments.

Albumins↗

Relationship between microtubules and Golgi apparatus in hepatocytes: a quantitative study during experimental nephrosis.

In many cell types, microtubules are preferentially associated with the Golgi apparatus. However, the existence of a functional link between these two organelles is still hypothetical. To gain insight into this question, the relationships between microtubules and the Golgi apparatus were studied in rat hepatocytes during experimental nephrosis induced by the aminonucleoside of puromycin. This condition is known to cause prolonged stimulation of plasma protein production by the hepatocytes. Rats were studied 2, 4, 5, 10 and 20 days after aminonucleoside injection. The amount of albumin was measured in serum and hepatic microsomes by laser immunonephelometry. The volume densities of microtubules around the Golgi apparatus and in the remaining cytoplasm were measured by ultrastructural morphometry. Changes of the Golgi apparatus were analysed by measuring the volume density of the whole organelle and the respective proportion of saccules and vesicles. Proteinuria began 5 days after aminonucleoside injection and was accompanied by a decrease in serum albumin and a rise in microsomal albumin. These changes were still more striking after 10 days, but protein and albumin levels were almost back to normal after 20 days. Concomitantly, the volume density of the microtubules increased significantly around the Golgi apparatus (32% after 10 days), and not in the remaining cytoplasm. The Golgi apparatus was enlarged (80% after 10 days) with a higher ratio of secretory vesicle to saccule volume densities. These results show that additional microtubules are present around the Golgi apparatus during the enhanced production of plasma proteins which occurs in nephrosis. They suggest that in hepatocytes, microtubules play a part in the Golgi apparatus function of plasma protein processing.

Animals↗

A morphologic and biochemical study of the transcriptional changes in rat liver during the acute inflammatory reaction.

Transcriptional activity in nuclei isolated from the liver of rats during the acute inflammatory reaction induced by a 24-hour treatment with turpentine was evaluated by biochemical and ultrastructural techniques. This experimental model was chosen because it is known to induce an increase in hepatic synthesis of several plasma proteins called acute phase reactants. Using an in vitro system for estimating the activity of RNA polymerases A and B as an approach to evaluate RNA synthesis, we have shown that the activity of enzyme A (responsible for pre-rRNA synthesis) was significantly enhanced, whereas the activity of enzyme B (responsible for giant heterogenous RNA synthesis) remained unchanged in treated rats compared with control rats. At the electron microscopic level, using the Miller technique to spread the nuclear contents, the non-nucleolar transcription units were similar in treated and control rats. In contrast to control rats, more nucleolar transcription units were vizualized in treated rats, although the ribonucleoprotein fibrils were less numerous; in addition, in the latter group 10 to 15 times more aggregates constituted of ribonucleoprotein fibrils and particles were observed, the morphology of which was in agreement with a nucleolar origin. These results suggest that, during the acute inflammatory reaction, there was no overall increase in giant heterogenous RNA synthesis, whereas an increase in rRNA synthesis might be observed.

Animals↗